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  • 101.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Response to 'Letter to the Editor' regarding the article 'The seasonal importance of serum 25-hydroxyvitamin D for bone mineral density in older women'2017Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, nr 3, s. 274-275Artikel i tidskrift (Övrigt vetenskapligt)
  • 102.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ferm, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ahlbom, Anders
    Pedersen, Nancy L.
    Genetic liability to fractures in the elderly2005Ingår i: Archives of Internal Medicine, ISSN 0003-9926, E-ISSN 1538-3679, Vol. 165, nr 16, s. 1825-30Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The genetic impact on the causation of osteoporotic fractures is unclear. A large twin study is ideally suited to determine the genetic liability to categories of fracture at various ages. METHODS: A cohort of all 33 432 Swedish twins born from 1896 to 1944 was used to evaluate the genetic liability to fracture occurrence in the elderly. The Swedish Inpatient Registry and computer-assisted telephone interviews enabled us to identify 6021 twins with any fracture, 3599 with an osteoporotic fracture, and 1055 with a hip fracture after the age of 50 years. RESULTS: Genetic variation in liability to fracture differed considerably by type of fracture and age. Less than 20% of the overall age-adjusted fracture variance was explained by genetic variation. The age-adjusted heritability of any osteoporotic fracture was slightly greater (0.27; 95% confidence interval [CI], 0.09-0.28), and for hip fracture alone, it was 0.48 (95% CI, 0.28-0.57). Heritability was not attenuated after further adjustment for several known osteoporotic covariates but was considerably greater for first hip fractures before the age of 69 years (0.68; 95% CI, 0.41-0.78) and between 69 and 79 years (0.47; 95% CI, 0.04-0.62) than for hip fractures after 79 years of age (0.03; 95% CI, 0.00-0.26). CONCLUSIONS: The importance of genetic factors in propensity to fractures depends on fracture site and age. The search for susceptibility genes and environmental factors that may modulate expression of these genes in younger elderly patients with hip fracture, the most devastating osteoporotic fracture, should be encouraged. Prevention of fractures in the oldest elderly should focus on lifestyle interventions.

  • 103.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Larsson, Susanna C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, SE-17177 Stockholm, Sweden.
    Serum 25-Hydroxyvitamin D Concentrations and Major Depression: A Mendelian Randomization Study2018Ingår i: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, nr 12, artikel-id 1987Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Whether vitamin D insufficiency is a contributing cause of depression remains unclear. We assessed whether serum 25-hydroxyvitamin D (S-25OHD) concentrations, the clinical marker of vitamin D status, were associated with major depression using Mendelian randomization. We used summary statistics data for six single-nucleotide polymorphisms significantly associated with S-25OHD concentrations in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) consortium and the corresponding data for major depression (n = 59,851 cases and 113,154 controls) from the Psychiatric Genomics Consortium. Genetically predicted S-25OHD concentrations were not associated with major depression. The odds ratio per genetically predicted one standard deviation decrease in S-25OHD concentrations was 1.02 (95% confidence interval 0.97-1.08; p = 0.44). The results of this study indicate that genetically lowered S-25OHD concentrations are not associated with increased risk of developing major depression.

  • 104.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Warensjö Lemming, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Long term calcium intake and rates of all cause and cardiovascular mortality: community based prospective longitudinal cohort study2013Ingår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 346, artikel-id f228Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    To investigate the association between long term intake of dietary and supplemental calcium and death from all causes and cardiovascular disease.

    DESIGN:

    Prospective longitudinal cohort study.

    SETTING:

    Swedish mammography cohort, a population based cohort established in 1987-90.

    PARTICIPANTS:

    61 433 women (born between 1914 and 1948) followed-up for a median of 19 years.

    MAIN OUTCOME MEASURES:

    Primary outcome measures, identified from registry data, were time to death from all causes (n=11 944) and cause specific cardiovascular disease (n=3862), ischaemic heart disease (n=1932), and stroke (n=1100). Diet was assessed by food frequency questionnaires at baseline and in 1997 for 38 984 women, and intakes of calcium were estimated. Total calcium intake was the sum of dietary and supplemental calcium.

    RESULTS:

    The risk patterns with dietary calcium intake were non-linear, with higher rates concentrated around the highest intakes (≥1400 mg/day). Compared with intakes between 600 and 1000 mg/day, intakes above 1400 mg/day were associated with higher death rates from all causes (hazard ratio 1.40, 95% confidence interval 1.17 to 1.67), cardiovascular disease (1 49, 1.09 to 2.02), and ischaemic heart disease (2.14, 1.48 to 3.09) but not from stroke (0.73, 0.33 to 1.65). After sensitivity analysis including marginal structural models, the higher death rate with low dietary calcium intake (<600 mg/day) or with low and high total calcium intake was no longer apparent. Use of calcium tablets (6% users; 500 mg calcium per tablet) was not on average associated with all cause or cause specific mortality but among calcium tablet users with a dietary calcium intake above 1400 mg/day the hazard ratio for all cause mortality was 2.57 (95% confidence interval 1.19 to 5.55).

    CONCLUSION:

    High intakes of calcium in women are associated with higher death rates from all causes and cardiovascular disease but not from stroke.

  • 105.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nordström, Peter
    Nordström, Anna
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Pedersen, Nancy L
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Impact of hip fracture on mortality: a cohort study in hip fracture discordant identical twins2014Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 29, nr 2, s. 424-431Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several studies have shown a long-lasting higher mortality after hip fracture but the reasons of the excess risk is not well understood. We aimed to determine whether there exists a higher mortality after hip fracture when controlling for genetic constitution, shared environment, comorbidity and lifestyle by use of a nation-wide cohort study in hip fracture discordant monozygotic twins. All 286 identical Swedish twin pairs discordant for hip fracture (1972-2010) were identified. Comorbidity and lifestyle information was retrieved by registers and questionnaire information. We used intrapair Cox regression to compute multivariable-adjusted hazard ratios (HRs) for death. During follow-up, 143 twins with a hip fracture died (50%) compared to 101 twins (35%) without a hip fracture. Through the first year after hip fracture, the rate of death increased four-fold in women (HR 3.71; 95% confidence interval (CI) 1.32-10.40) and seven-fold in men (HR 6.67; 95% CI 1.47-30.13). The increased rate in women only persisted during the first year after hip fracture (HR after 1 year 0.99; 95% CI 0.66-1.50), whereas the corresponding HR in men was 2.58 (95% CI 1.02-6.62). The higher risk in men after the hip fracture event was successively attenuated during follow-up. After 5 years, the hazard ratio in men with a hip fracture was 1.19 (95% CI 0.29-4.90). On average, the hip fracture contributed to 0.9 years of life lost in women (95% CI 0.06-1.7) and 2.7 years in men (95% CI 1.7-3.7). The potential years of life lost associated with the hip fracture was especially pronounced in older men (>75 years), with an average loss of 47% (95% CI 31-61) of the expected remaining lifetime. We conclude that both women and men display a higher mortality after hip fracture independent of genes, comorbidity and lifestyle.

  • 106.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Olofsson, Helena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Jensevik, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Berglund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Leisure physical activity and the risk of fracture in men2007Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 4, nr 6, s. 1094-1100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Data from previous studies are inconsistent, and it is therefore uncertain whether, to what extent, and at what level leisure physical activity influences the risk of osteoporotic fractures in men. METHODS AND FINDINGS: A cohort of 2,205 men, 49-51 y of age, was enrolled in a longitudinal, population-based study. Leisure physical activity and other lifestyle habits were established at baseline and at ages 60, 70, 77, and 82 y. During 35 y of follow-up, 482 men had at least one fracture. Cox's proportional hazards regression was used to determine hazard ratios (HRs) of fracture associated with time-dependent physical activity habits and covariates. Men with a sedentary lifestyle (HR 2.56, 95% confidence interval 1.55-4.24) or men who walked or bicycled only for pleasure (HR 1.61, 95% confidence interval 1.10-2.36) had an increased adjusted risk of hip fracture compared with men who participated in regular sports activities for at least 3 h/wk. At the end of follow-up, 8.4% of the men with a high physical activity, 13.3% of the men with a medium physical activity, and 20.5% of the men with a low physical activity had suffered a hip fracture. According to the estimation of population-attributable risk, one third of all hip fractures could be prevented by participation in regular sports activities. High activity also conferred a reduced overall fracture risk. CONCLUSIONS: Our data indicate that regular sports activities can reduce the risk of fractures in older men.

  • 107.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mitchell, Adam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    The seasonal importance of serum 25-hydroxyvitamin D for bone mineral density in older women2017Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, nr 2, s. 167-178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The impact of season when determining a serum 25-hydroxyvitamin D (S-25OHD) cut-off level for optimal bone health is unknown.

    OBJECTIVE: To investigate the relative importance of S-25OHD for bone mineral density (BMD) by season.

    METHODS: A subcohort of 5002 Swedish women (mean age 68 years), randomly selected from a large population-based longitudinal cohort study with repeat dietary and lifestyle information, was enrolled during 2003-2009 for a clinical examination, which included dual-energy X-ray absorptiometry and collection of fasting blood samples. Categories of vitamin D status were determined by S-25OHD (measured by HPLC-MS/MS).

    RESULTS: In samples collected during summer, we found a gradual increase in BMD of the total hip up to a S-25OHD level of 40 nmol L(-1) (6% of the cohort). In women with S-25OHD concentrations below 30 nmol L(-1) during summer, adjusted BMD was 11% lower [95% confidence interval (CI) 3-19] and in those with S-25OHD levels of 30-40 nmol L(-1) BMD was 6% lower (95% CI 1-11), compared with women with S-25OHD levels above 80 nmol L(-1) . Low S-25OHD concentrations during summer (<30 nmol L(-1) ) were also associated with higher adjusted relative risk of osteoporosis (4.9; 95% CI 2.9-8.4) compared with concentrations above 80 nmol L(-1) . By contrast, no differences in mean BMD values between categories of S-25OHD were found during winter.

    CONCLUSIONS: Summer concentrations of S-25OHD appear to be the most useful to predict BMD, whereas winter levels have limited value. To determine a S-25OHD cut-off level for vitamin D deficiency, it may be necessary to take into account the season of blood collection.

  • 108.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Intake and serum concentrations of α-tocopherol in relation to fractures in elderly women and men: 2 cohort studies2014Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 99, nr 1, s. 107-114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    A reduction in the formation of free radicals and oxidative stress might reduce the rate of bone loss and muscle wasting.

    OBJECTIVE:

    The objective was to determine whether α-tocopherol intake or serum concentrations are associated with fracture risk in older women and men.

    DESIGN:

    Two cohort studies, the Swedish Mammography Cohort (SMC; n = 61,433 women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1138 men), were used.

    RESULTS:

    During 19 y of follow-up, 14,738 women in the SMC experienced a first fracture at any site (3871 hip fractures). A higher hip fracture rate was observed with lower intakes of α-tocopherol. Compared with the highest quintile of intake, the lowest quintile had a multivariable-adjusted HR of 1.86 (95% CI: 1.67, 2.06). The HR of any fracture was 1.20 (95% CI: 1.14, 1.28). α-Tocopherol-containing supplement use was associated with a reduced rate of hip fracture (HR: 0.78; 95% CI: 0.65, 0.93) and any fracture (HR: 0.86; 95% CI: 0.78, 0.94). Compared with the highest quintile of α-tocopherol intake in ULSAM (follow-up: 12 y), lower intakes (quintiles 1-4) were associated with a higher rate of hip fracture (HR: 3.33; 95% CI: 1.43, 7.76) and any fracture (HR: 1.84; 95% CI: 1.18, 2.88). The HR for hip fracture in men for each 1-SD decrease in serum α-tocopherol was 1.58 (95% CI: 1.13, 2.22) and for any fracture was 1.23 (95% CI: 1.02, 1.48).

    CONCLUSION:

    Low intakes and low serum concentrations of α-tocopherol are associated with an increased rate of fracture in elderly women and men.

  • 109.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Jacobsson, Annica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Grundberg, Elin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Stiger, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ljunghall, Sverker
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    The positive effect of dietary vitamin D intake on bone mineral density in men is modulated by the polyadenosine repeat polymorphism of the vitamin D receptor2006Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 39, nr 6, s. 1343-1351Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Few studies have considered the dietary influence of vitamin D intake on bone mineral density (BMD). Numerous studies have examined the association between VDR polymorphism and BMD, but no previous study has examined the joint influence of dietary vitamin D intake and VDR polymorphism on BMD. METHODS: We therefore conducted a study in 230 men aged 41-76 years of age. BMD was measured with DXA. A second bone scan was performed on average 2.7 years after the first investigation. Dietary habits were assessed by 14 dietary 24-h recall interviews. The polyadenosine (A) VDR genotypes were determined. RESULTS: Dietary vitamin D intake was associated with BMD at all sites, also after multivariate adjustment. Those in the highest quintile of intake had 9% higher femoral neck BMD (p = 0.004), 6% higher BMD at the lumbar spine (p = 0.06) and 5% higher total body BMD (p = 0.003) compared to men in the lowest quintile of dietary vitamin D intake. However, the positive association between vitamin D intake and BMD was especially apparent among those with the L/L polyadenosine (A) VDR genotype explaining between 10 and 15% of the variability in BMD depending on site (p < 0.004). There was furthermore a trend, in the lumbar spine, of less reduction in BMD with increasing vitamin D intake (p = 0.07) but not at the other sites. Calcium intake conferred no association with BMD. CONCLUSIONS: Our results indicate that the extent of positive association between dietary vitamin D intake and BMD in men is dependent on VDR polymorphism, a novel conceivable important gene-environmental interaction.

  • 110.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Langenskiöld, Sophie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Hälsoekonomi.
    Basu, Samar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Oxidativ stress och inflammation.
    Warensjö Lemming, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Milk intake and risk of mortality and fractures in women and men: cohort studies2014Ingår i: British Medical Journal, ISSN 1756-1833, Vol. 349, s. g6015-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To examine whether high milk consumption is associated with mortality and fractures in women and men.

    DESIGN: Cohort studies.

    SETTING: Three counties in central Sweden.

    PARTICIPANTS: Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997.

    MAIN OUTCOME MEASURE: Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture.

    RESULTS: During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).

    CONCLUSIONS: High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.

  • 111.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Unit Nutrit Epidemiol, Stockholm, Sweden..
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Milk, Fruit and Vegetable, and Total Antioxidant Intakes in Relation to Mortality Rates: Cohort Studies in Women and Men2017Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 185, nr 5, s. 345-361Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High milk consumption might shorten life span through increased oxidative stress. We aimed to determine whether higher mortality rates with high milk consumption are modified by fruit and vegetable intake or total antioxidant intake (oxygen radical absorbance capacity). We used information from food frequency questionnaires completed by 61,420 women in a Swedish cohort (22,391 deaths from the 1987-1990 baseline onward), 36,714 women from a second survey (1997) of this cohort, and 45,280 Swedish men (15,478 deaths from the 1998 baseline onward). Compared with low consumption of milk (< 1 glass/day) and high consumption of fruits/vegetables (>= 5 servings/day), time-updated information revealed an adjusted hazard ratio for death of 2.79 (95% confidence interval (CI): 2.42, 3.21) in women who consumed >= 3 glasses of milk/day and < 1 serving/day of fruit/vegetables and a hazard ratio of 1.60 (95% CI: 1.40, 1.82) in women who consumed the same amount of milk but >= 5 servings/day of fruits/vegetables. The same comparisons in men, based on a single food frequency questionnaire, displayed hazard ratios of 1.31 (95% CI: 1.14, 1.51) and 1.07 (95% CI: 0.97, 1.18), respectively. Total antioxidant consumption showed similar patterns as fruit/vegetable intakes. Dietary antioxidant intake, especially in women, seems to modify the elevated death rate associated with high milk consumption.

  • 112.
    Michaëlsson, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Warensjö, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Intake of milk or fermented milk combined with fruit and vegetable consumption in relation to hip fracture rates: A cohort study of Swedish women.2018Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, nr 3, s. 449-457Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Milk products may differ in pro-oxidant properties and their effects on fracture risk could potentially be modified by the intake of foods with antioxidant activity. In the population-based Swedish Mammography Cohort study, we aimed to determine how milk and fermented milk combined with fruit and vegetable consumption are associated with hip fracture. Women born 1914-1948 (n=61 240) answered food frequency and lifestyle questionnaires in 1987-1990 and 38 071 women contributed with updated information in 1997. During a mean follow-up of 22 years, 5827 women had a hip fracture (ascertained via official register data). Compared with a low intake of milk (<1 glass/day) and a high intake of fruits and vegetables (≥5 servings/day), a high intake of milk (≥3 glasses/day) with a concomitant low intake of fruits and vegetables (<2 servings/day) resulted in a HR of 2.49 (95% CI, 2.03-3.05). This higher hip fracture rate among high consumers of milk was only modestly attenuated with a concomitant high consumption of fruit and vegetables (HR 2.14; 95% CI 1.69-2.71). The combination of fruits and vegetables with fermented milk (yogurt or soured milk) yielded a different pattern with lowest rates of hip fracture in high consumers: HR 0.81 (95% CI, 0.68-0.97) for ≥2 servings/day of fermented milk and ≥5 servings/day of fruits and vegetables compared with low consumption of both fruit and vegetables and fermented milk. We conclude that the amount and type of dairy products as well as fruit and vegetable intake are differentially associated with hip fracture rates in women.

  • 113.
    Mirza, Majd A. I.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Larsson, Tobias E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population2009Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 207, nr 2, s. 546-551Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fibroblast growth factor-23 (FGF23) is a hormonal regulator of circulating phosphate and vitamin D levels. Serum FGF23 is elevated in chronic kidney disease (CKD) and is a prognostic marker of poor outcomes, such as faster CKD progression and increased mortality in hemodialysis patients. Despite the high prevalence of cardiovascular disease in CKD, the relation between circulating FGF23 and cardiovascular risk factors, both in CKD and in the community, has not been studied in detail. We evaluated the relation between FGF23, left ventricular mass index (LVMI), hypertrophy (LVH) and LV geometry, employing the community-based PIVUS cohort. In total, 795 Swedish men and women aged 70 were included of which 164 had an age-adjusted diminished renal function (estimated glomerular filtration rate<60mL/min/1.73m(2)). FGF23 was positively associated with LVMI (beta=0.11, CI 0.01-0.18), with increased odds for the presence of LVH (OR 1.28, CI 1.09-1.51) and for concentric hypertrophy (OR 1.45, CI 1.19-1.77) in the whole population. All associations were stronger in subjects with eGFR<60mL/min/1.73m(2) (beta=0.30, CI 0.15-0.46 for LVMI; OR 1.86, CI 1.30-2.67 for the presence of LVH; OR 1.83, CI 1.17-2.85 and OR 1.87, CI 1.08-3.22 for concentric and eccentric hypertrophy, respectively). The results were essentially unaltered in multivariate models. In summary, elevated serum FGF23 levels, even within the normal range, are associated with increased LVMI and increased risk for the presence of LVH in elderly subjects. Additional longitudinal studies that evaluate the predictive power of FGF23 and whether FGF23 has additional clinical applications are needed.

  • 114.
    Mitchell, Adam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Type 2 Diabetes in Relation to Hip Bone Density, Area, and Bone Turnover in Swedish Men and Women: A Cross-Sectional Study2018Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 103, nr 5, s. 501-511Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Men and women with type 2 diabetes mellitus (T2DM) have higher risk of hip fracture, but the mechanisms are not fully understood. We aimed to investigate how T2DM, glucose, and insulin were associated with femoral bone mineral density (BMD), bone mineral area (BMA), and bone turnover markers. We used two cross-sectional cohorts: the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 452, mean age 82 years) and the Swedish Mammography Cohort Clinical (SMCC, n = 4713, mean age 68 years). We identified men and women with normal fasting glucose (NFG), impaired fasting plasma glucose (IFG), and T2DM. BMD and BMA at the total hip and femoral shaft were measured using dual energy X-ray absorptiometry (DXA). Bone turnover markers; CrossLaps and osteocalcin were measured in women. Linear regression models were applied. Men and women showed a progressively higher BMD following the clinical cutoffs of fasting glucose from NFG to IFG to T2DM. In contrast, there was a progressively lower BMA. Men and women with T2DM, compared to those with NFG, had lower BMA at the total hip (- 1.7%; 95% CI - 3.2, - 0.2 and - 1.0%; 95% CI - 1.6, - 0.4) and the femoral shaft (- 2.0%; 95% CI - 3.5, - 0.4 and - 0.6%; 95% CI - 1.2, - 0.01), respectively. T2DM was associated with lower concentrations of CrossLaps (- 8.1%; 95% CI - 12.7, - 3.6) and osteocalcin (- 15.2%; 95% CI - 19.0, - 11.2). These cross-sectional results indicate that those with T2DM have smaller bone area and lower bone turnover, which could increase the risk of hip fracture.

  • 115.
    Montazerolghaem, Maryam
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Jacobson Rasmusson, Annica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Karlsson Ott, Marjam
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Simvastatin-doped pre-mixed calcium phosphate cement inhibits osteoclast differentiation and resorption2016Ingår i: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 27, nr 5, artikel-id 83Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Simvastatin, a cholesterol lowering drug, has been shown to have positive effects on fracture healing and bone regeneration based on its dual effect; bone anabolic and anti-resorptive. In this study the focus has been on the anti-resorptive effect of the drug and its impact on the degradation of acidic calcium phosphate cement. The drug was added to the pre-mixed acidic cement in three different doses (0.1, 0.25 and 0.5 mg/g cement) and the release was measured. Furthermore the effect of the loaded cements on osteoclast differentiation and resorption was evaluated by TRAP activity, number of multinucleated cells, gene expression and calcium ion concentration in vitro using murine bone marrow macrophages. The simvastatin did not affect the cell proliferation while it clearly inhibited osteoclastic differentiation at all three doses as shown by TRAP staining, TRAP activity and gene expression. Consistent with these results, simvastatin also impaired resorption of cements by osteoclasts as indicated by reduced calcium ion concentrations. In conclusion, our findings suggest that simvastatin-doped pre-mixed acidic calcium phosphate cement inhibits the osteoclastic mediated resorption of the cement thus slowing down the degradation rate. In addition with simvastatin's bone anabolic effect it makes the cement-drug combination a promising bone graft material, especially useful for sites with compromised bone formation.

  • 116.
    Montazerolghaem, Maryam
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Karlsson Ott, Marjam
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Jacobson Rasmusson, Annica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Resorption of Monetite Calcium Phosphate Cement by Mouse Bone Marrow derived Osteoclasts2015Ingår i: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 52, s. 212-218Artikel i tidskrift (Refereegranskat)
  • 117.
    Olofsson, Helena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Mohsen, Rawya
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lithell, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Smoking and the Risk of Fracture in Older Men2005Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 20, nr 7, s. 1208-15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of smoking on fracture risk in older men was studied within a longitudinal population-based cohort study. Using time-dependent exposure information and analysis, smoking was detected to be a stronger, dose-dependent and a more long lasting risk factor for fracture than has previously been estimated. INTRODUCTION: Although several studies have indicated a negative influence of smoking on fracture risk in women, there are few studies in men. No study in either sex has considered that smoking exposure may vary during follow-up in a cohort study. There is a need for a prospective study with repeated measures to analyze smoking exposure and fracture risk in men. MATERIALS AND METHODS: A total of 2322 men, 49-51 years of age, were enrolled in a longitudinal, population-based cohort study. Smoking status and other lifestyle habits were established at baseline and additionally at 60, 70, and 77 years of age. One or more fractures were documented in 272 men during 30 years of follow-up. Cox proportional hazards regression was used to determine the rate ratio (RR) of fracture according to time-dependent smoking habits and covariates. RESULTS: The overall adjusted fracture risk was increased in current (RR, 2.71; 95% CI, 1.86-3.95) and former smokers (RR, 1.66, 95% CI; 1.18-2.34), and persistent until 30 years after cessation. Among current smokers, the adjusted risk of any fracture increased by 30% (95% CI, 6-58%) for every 5 g of tobacco smoked each day. Smoking duration did not substantially influence fracture risk in either current or former smokers. One-half (52%; 95% CI, 35-65%) of all fractures were attributable to current smoking. CONCLUSIONS: Tobacco smoking seems to be a long-lasting major risk factor for fracture in older men, and the risks depends both on recency of smoking and on the daily amount of tobacco smoked, rather than smoking duration.

  • 118.
    Olsson, Erika
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Karlström, Brita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Cederholm, Tommy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Sjögren, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Kilander, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Vitamin D is not associated with incident dementia or cognitive impairment: an 18-y follow-up study in community-living old men2017Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 105, nr 4, s. 936-943Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Vitamin D has been implicated as being important for maintaining cognitive function in old age. Results from longitudinal studies examining the association of vitamin D with incident dementia and cognitive impairment have been inconsistent. Objective: We investigated the relation between vitamin D, assessed in 3 different ways, and the risk of dementia. Design: We measured plasma 25-hydroxyvitamin D [25(OH) D] with the use of high-performance liquid chromatography-mass spectrometry, assessed dietary vitamin D intake with the use of 7-d dietary records, and created a vitamin D-synthesis genetic risk score (GRS) at baseline (1991-1995) in a cohort of 1182 Swedish men (mean age: 71 y). In a maximum of 18 y (median: 12 y) of follow-up, 116 men developed Alzheimer disease, 64 men developed vascular dementia, and 250 men developed all-cause dementia. An additional 80 men declined in cognitive function as assessed with the use of the Mini-Mental State Examination. Adjusted HRs and ORs were calculated with the use of Cox and logistic regressions. Results: The mean +/- SD plasma 25(OH) D concentration was 68.7 +/- 19.1 nmol/L. Plasma 25(OH) D, dietary vitamin D intake, and vitamin D-synthesis GRS were not associated with any cognitive outcomes (crude and adjusted HRs and ORs were similar to 1.0 for all continuous exposures). The adjusted HR for all-cause dementia was 0.88 (95% CI: 0.59, 1.31) in men with plasma 25(OH) D concentrations <= 50 compared with >75 nmol/L. The adjusted HR for all-cause dementia was 0.92 (95% CI: 0.63, 1.32) for the lowest compared with highest tertiles of vitamin D intake. The adjusted HR for the continuous GRS for all-cause dementia was 1.04 (95% CI: 0.91, 1.19). Conclusion: In this cohort study, we show that there is no association between baseline vitamin D status and long-term risk of dementia or cognitive impairment over an 18-y period of time.

  • 119.
    Scordo, Maria Gabriella
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Stjernberg, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Edvardsson, Anne Maria
    Wadelius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Warfarin-noscapine interaction: a series of four case reports2008Ingår i: The Annals of Pharmacotherapy, ISSN 1060-0280, E-ISSN 1542-6270, Vol. 42, nr 3, s. 448-450Artikel i tidskrift (Refereegranskat)
  • 120.
    Snellman, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lemming, Eva Warensjo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Michaelsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Long-Term Dietary Vitamin D Intake and Risk of Fracture and Osteoporosis: A Longitudinal Cohort Study of Swedish Middle-aged and Elderly Women2014Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 99, nr 3, s. 781-790Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: The importance of dietary vitamin D for osteoporotic fracture prevention is uncertain. Objective: Our objective was to investigate associations between dietary vitamin D intake with risk of fracture and osteoporosis. Design and Participants: In the population-based Swedish Mammography Cohort (including 61 433 women followed for 19 years), diet was assessed by repeated food frequency questionnaires. Setting: The study was conducted in 2 municipalities in central Sweden. Main Outcome Measure: Incident fractures were identified from registry data. In a subcohort (n = 5022), bone mineral density was determined by dual-energy x-ray absorptiometry and serum 25-hydroxyvitamin D was measured using HPLC-tandem mass spectrometry. Results: A total of 14 738 women experienced any type of first fracture during follow-up, and 3871 had a hip fracture. Multivariable-adjusted hazard ratio (HR) for any first fracture was 0.96 (95% confidence interval, 0.92-1.01) for the lowest (mean, 3.1 mu g/d) and 1.02 (0.96-1.07) for the highest (mean, 6.9 mu g/d) quintile compared with the third quintile of vitamin D intake. The corresponding HR for a first hip fracture was 1.02 (0.96-1.08) for the lowest and 1.14 (1.03-1.26) for the highest quintile. Intakes >10 mu g/d, compared with <5 mu g/d, conferred an HR of 1.02 (0.92-1.13) for any fracture and an HR of 1.27 (1.03-1.57) for hip fracture. The intake of vitamin D did not affect the odds for osteoporosis, although higher levels were associated with higher bone mineral density (0.3%-2%, P < .0001). A positive association was observed between vitamin D intake and serum 25-hydroxyvitamin D. Conclusions: Dietary intakes of vitamin D seem of minor importance for the occurrence of fractures and osteoporosis in community-dwelling Swedish women.

  • 121.
    Snellman, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Serum 25-hydroxyvitamin D in relation to BMD and fractures in a Swedish cohort of women and menManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background/aim

    Vitamin D insufficiency has been suggested to be common and to cause osteoporotic fractures. Results from previous studies are inconsistent. The aim of our study was to assess if circulating vitamin D is associated with incident fractures and bone mineral density (BMD) among elderly Swedish men and women.

    Method

    A population-based cohort consisting of 1002 Swedish men and women, aged 70-years at baseline with a setting at latitude 60o north, was followed for 7 years. Serum vitamin D (25(OH)D) at baseline was analysed by an immunoassay. Fractures during follow-up were identified from registry data and BMD was measured with DXA. Association between 25(OH)D levels and time to fracture was our primary endpoint and BMD our secondary outcome.

    Result

    Mean S-25(OH)Dlevel was 58 (SD 20) nmol/L and 38% of the participants had levels <50 nmol/L. After multivariable adjustment, S-25(OH)D was only associated with total body BMD among men (P=0.03) but the relation was weak. Each SD increase in S-25(OH)D (approximately 20 nmol/L) conferred a 1% increase in total body BMD. Low vitamin D levels were not associated with lower BMD at the total hip or the lumbar spine in men or women. During follow-up, 155 (15%) of the participants sustained a fracture. No association between 25(OH)D and the rate of fracture was evident. The lowest quintile compared to highest quintile of 25(OH)D conferred a HR of 1.13 (95% CI 0.65-1.94).

    Conclusion

    In a general population of elderly Swedish men and women, serum vitamin D is not a strong determinant of fractures or of low bone mineral density.

  • 122.
    Snellman, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Warensjö-Lemming, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Institutet för miljömedicin, Karolinska Institutet.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Long-term dietary vitamin D intake and risk of fracture and osteoporosis: a longitudinal cohort study of Swedish middle-aged and elderly women2012Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, nr Suppl 1, s. S65-S65Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Context: Vitamin D deficiency may lead to osteoporosis and fracture but the importance of dietary vitamin D intake for skeletal health in adults is uncertain.

    Objective: To investigate associations between long-term dietary intake of vitamin D with risk of fractures and osteoporosis.

    Design: A prospective longitudinal cohort study.

    Setting: The population-based Swedish Mammography Cohort and the subcohort SMC Clinical.

    Participants: 61,433 women (age range 38 to 76 years) were followed for 19 years. Of these, 5,022 participated in the subcohort. Diet was assessed by repeated food frequency questionnaires.   

    Main outcome measures: Incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort.

    Results: 14,738 women experienced any type of first fracture during follow-up, with 3,871 of these being hip fractures. Twenty percent of the women in the subcohort were classified as osteoporotic. A multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI) for any first fracture was 0.96 (95% CI 0.92-1.01) for the lowest and 1.02 (95% CI 0.96-1.07) for the highest quintile when compared with the third quintile of vitamin D intake. The corresponding HR for a first hip fracture was 1.02 (95% CI, 0.96-1.08) for the lowest and 1.14 (95% CI, 1.03-1.26) for the highest quintile. The odds ratio of osteoporosis by quintiles of vitamin D intake was 1.20 (95% CI, 0.85-1.71) for the lowest and 0.99 (95% CI, 0.78-1.25) for the highest quintile. Bone mineral density, however, were 2% higher at the lumbar spine and 0.3% higher at the total hip in women with highest vs. women with lowest intake of vitamin D (p<0.0001).

    Conclusions: Dietary intake of vitamin D seems to be of minor importance for the occurrence of fractures and osteoporosis in community-dwelling Swedish middle-aged and elderly women.

  • 123.
    Snellman, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Berglund, Lars
    Wernroth, Lisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniskt forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Determining Vitamin D Status: A Comparison between Commercially Available Assays2010Ingår i: PLoS ONE, ISSN 1932-6203, Vol. 5, nr 7, s. e11555-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Vitamin D is not only important for bone health but can also affect the development of several non-bone diseases. The definition of vitamin D insufficiency by serum levels of 25-hydroxyvitamin D depends on the clinical outcome but might also be a consequence of analytical methods used for the definition. Although numerous 25-hydroxyvitamin D assays are available, their comparability is uncertain. We therefore aim to investigate the precision, accuracy and clinical consequences of differences in performance between three common commercially available assays. Methodology/Principal Findings: Serum 25-hydroxyvitamin D levels from 204 twins from the Swedish Twin Registry were determined with high-pressure liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (HPLCAPCI-MS), a radioimmunoassay (RIA) and a chemiluminescent immunoassay (CLIA). High inter-assay disagreement was found. Mean 25-hydroxyvitamin D levels were highest for the HPLC-APCI-MS technique (85 nmol/L, 95% CI 81-89), intermediate for RIA (70 nmol/L, 95% CI 66-74) and lowest with CLIA (60 nmol/L, 95% CI 56-64). Using a 50-nmol/L cut-off, 8% of the subjects were insufficient using HPLC-APCI-MS, 22% with RIA and 43% by CLIA. Because of the heritable component of 25-hydroxyvitamin D status, the accuracy of each method could indirectly be assessed by comparison of within-twin pair correlations. The strongest correlation was found for HPLC-APCI-MS (r = 0.7), intermediate for RIA (r = 0.5) and lowest for CLIA (r = 0.4). Regression analyses between the methods revealed a non-uniform variance (p<0.0001) depending on level of 25-hydroxyvitamin D. Conclusions/Significance: There are substantial inter-assay differences in performance. The most valid method was HPLCAPCI-MS. Calibration between 25-hydroxyvitamin D assays is intricate.

  • 124.
    Snellman, Greta
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Olofsson, Sylvia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Wolk, Alicja
    Pedersen, Nancy L.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study2009Ingår i: PloS one, ISSN 1932-6203, Vol. 4, nr 11, s. e7747-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Although environmental factors, mainly nutrition and UV-B radiation, have been considered major determinants of vitamin D status, they have only explained a modest proportion of the variation in serum 25-hydroxyvitamin D. We aimed to study the seasonal impact of genetic factors on serum 25-hydroxyvitamin D concentrations. METHODOLOGY/PRINCIPAL FINDINGS: 204 same-sex twins, aged 39-85 years and living at northern latitude 60 degrees, were recruited from the Swedish Twin Registry. Serum 25-hydroxyvitamin D was analysed by high-pressure liquid chromatography and mass spectrometry. Genetic modelling techniques estimated the relative contributions of genetic, shared and individual-specific environmental factors to the variation in serum vitamin D. The average serum 25-hydroxyvitamin D concentration was 84.8 nmol/l (95% CI 81.0-88.6) but the seasonal variation was substantial, with 24.2 nmol/l (95% CI 16.3-32.2) lower values during the winter as compared to the summer season. Half of the variability in 25-hydroxyvitamin D during the summer season was attributed to genetic factors. In contrast, the winter season variation was largely attributable to shared environmental influences (72%; 95% CI 48-86%), i.e., solar altitude. Individual-specific environmental influences were found to explain one fourth of the variation in serum 25-hydroxyvitamin D independent of season. CONCLUSIONS/SIGNIFICANCE: There exists a moderate genetic impact on serum vitamin D status during the summer season, probably through the skin synthesis of vitamin D. Further studies are warranted to identify the genes impacting on vitamin D status.

  • 125.
    Stattin, Karl
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Elmstahl, Solve
    Lund Univ, Dept Clin Sci, Div Geriatr Med, Lund, Sweden.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Unit Cardiovasc & Nutr Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Warensjö Lemming, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Physical activity is associated with a large number of cardiovascular-specific proteins: Cross-sectional analyses in two independent cohorts2019Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 26, nr 17, s. 1865-1873, artikel-id UNSP 2047487319868033Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims:We aimed to discover and replicate associations between leisure-time physical activity and cardiovascular candidate plasma protein biomarkers and to examine whether the associations were independent of body fat. Methods:We used cross-sectional data from two population-based cohorts, the EpiHealth (discovery cohort; n = 2239) and the Swedish Mammography Cohort - Clinical (SMCC; replication cohort; n = 4320). Physical activity during leisure time was assessed using questionnaires, and plasma concentrations of 184 proteins were assayed using the Olink Proseek Multiplex Cardiovascular 2 and 3 kits. We applied adjusted linear regression models using the False Discovery Rate to control for multiple testing in discovery. Results:In EpiHealth, physical activity was associated with 75 cardiovascular plasma biomarkers, of which 28 associations were verified (replicated) in SMCC. Findings include seven novel associations in human: paraoxonase 3, cystatin B, cathepsin Z, alpha-L-iduronidase, prostasin, growth differentiation factor 2 and tumour necrosis factor alpha receptor superfamily member 11A. Estimates for associations were similar across tertiles of body fat and physical activity was associated with four biomarkers independent of body fat percentage: paraoxonase 3, cystatin B, fatty acid-binding protein 4 and interleukin-1 receptor antagonist. Conclusion: Leisure-time physical activity was associated with 28 cardiovascular-specific proteins; four associations were independent of body fat. Biomarkers in novel associations are involved in several atherosclerotic processes including regulation of low-density lipoprotein oxidation, protein degradation and immune cell adhesion and migration. Further research into these pathways may yield new insights into how physical activity affects cardiovascular health.

  • 126.
    Sulku, Johanna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Jansson, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Malinovschi, Andrei
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Ställberg, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Bröms, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Högman, Marieann
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lung- allergi- och sömnforskning.
    Lisspers, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Hammarlund-Udenaes, Margareta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Nielsen, Elisabet I.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    A Cross-Sectional Study Assessing Appropriateness Of Inhaled Corticosteroid Treatment In Primary And Secondary Care Patients With COPD In Sweden2019Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 14, s. 2451-2460Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Inhaled corticosteroids (ICS) are often more widely prescribed in the treatment of chronic obstructive pulmonary disease (COPD) than what is recommended in the guidelines. The aim of this study was to evaluate the appropriateness of ICS treatment in COPD patients using the algorithm proposed by the International Primary Care Respiratory Group (IPCRG) and to identify factors associated with ICS treatment.

    Patients and methods: Appropriateness of ICS therapy was studied with respect to concomitant asthma, history of exacerbations and blood eosinophils (B-Eos) in a Swedish cohort of primary and secondary care patients with COPD. Factors associated with ICS were investigated using multivariable logistic regression.

    Results: Triple treatment was found to be the most common treatment combination, used by 46% of the 561 included patients, and in total 63% were using ICS. When applying the IPCRG algorithm, there was a possible indication for discontinuation of ICS in 55% of the patients with ICS treatment. Of the patients not using ICS, 18% had an indication for starting such treatment. The strongest factors associated with ICS therapy were frequent exacerbations (aOR 8.61, 95% CI 4.06, 20.67), secondary care contacts (aOR 6.99, 95% CI 2.48, 25.28) and very severe airflow limitation (aOR 5.91, 95% CI 1.53, 26.58).

    Conclusion: More than half of the COPD patients on ICS met the criteria where withdrawal of the treatment could be tried. There was, however, also a subgroup of patients not using ICS for whom there was an indication for starting ICS treatment. Patients using ICS were characterized by more frequent exacerbations and lower lung function.

  • 127. Vimaleswaran, Karani S.
    et al.
    Berry, Diane J.
    Lu, Chen
    Tikkanen, Emmi
    Pilz, Stefan
    Hiraki, Linda T.
    Cooper, Jason D.
    Dastani, Zari
    Li, Rui
    Houston, Denise K.
    Wood, Andrew R.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Vandenput, Liesbeth
    Zgaga, Lina
    Yerges-Armstrong, Laura M.
    McCarthy, Mark I.
    Dupuis, Josee
    Kaakinen, Marika
    Kleber, Marcus E.
    Jameson, Karen
    Arden, Nigel
    Raitakari, Olli
    Viikari, Jorma
    Lohman, Kurt K.
    Ferrucci, Luigi
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Ingelsson, Erik
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lorentzon, Mattias
    Salomaa, Veikko
    Campbell, Harry
    Dunlop, Malcolm
    Mitchell, Braxton D.
    Herzig, Karl-Heinz
    Pouta, Anneli
    Hartikainen, Anna-Liisa
    Streeten, Elizabeth A.
    Theodoratou, Evropi
    Jula, Antti
    Wareham, Nicholas J.
    Ohlsson, Claes
    Frayling, Timothy M.
    Kritchevsky, Stephen B.
    Spector, Timothy D.
    Richards, J. Brent
    Lehtimaki, Terho
    Ouwehand, Willem H.
    Kraft, Peter
    Cooper, Cyrus
    Maerz, Winfried
    Power, Chris
    Loos, Ruth J. F.
    Wang, Thomas J.
    Jaervelin, Marjo-Riitta
    Whittaker, John C.
    Hingorani, Aroon D.
    Hyppoenen, Elina
    Causal Relationship between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts2013Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 10, nr 2, s. e1001383-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH) D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. Methods and Findings: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH) D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH) D (p = 6.52x10(-27)). The BMI allele score was associated both with BMI (p = 6.30x10(-62)) and 25(OH) D (20.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH) D (p <= 8.07x10(-57) for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH) D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH) D with BMI, a finding that was confirmed using data from the GIANT consortium (p >= 0.57 for both vitamin D scores). Conclusions: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH) D, while any effects of lower 25(OH) D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

  • 128. Vimaleswaran, Karani S
    et al.
    Cavadino, Alana
    Berry, Diane J
    Jorde, Rolf
    Dieffenbach, Aida Karina
    Lu, Chen
    Alves, Alexessander Couto
    Heerspink, Hiddo J Lambers
    Tikkanen, Emmi
    Eriksson, Joel
    Wong, Andrew
    Mangino, Massimo
    Jablonski, Kathleen A
    Nolte, Ilja M
    Houston, Denise K
    Ahluwalia, Tarunveer Singh
    van der Most, Peter J
    Pasko, Dorota
    Zgaga, Lina
    Thiering, Elisabeth
    Vitart, Veronique
    Fraser, Ross M
    Huffman, Jennifer E
    de Boer, Rudolf A
    Schöttker, Ben
    Saum, Kai-Uwe
    McCarthy, Mark I
    Dupuis, Josée
    Herzig, Karl-Heinz
    Sebert, Sylvain
    Pouta, Anneli
    Laitinen, Jaana
    Kleber, Marcus E
    Navis, Gerjan
    Lorentzon, Mattias
    Jameson, Karen
    Arden, Nigel
    Cooper, Jackie A
    Acharya, Jayshree
    Hardy, Rebecca
    Raitakari, Olli
    Ripatti, Samuli
    Billings, Liana K
    Lahti, Jari
    Osmond, Clive
    Penninx, Brenda W
    Rejnmark, Lars
    Lohman, Kurt K
    Paternoster, Lavinia
    Stolk, Ronald P
    Hernandez, Dena G
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hagström, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mellström, Dan
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Tzoulaki, Ioanna
    McLachlan, Stela
    Theodoratou, Evropi
    Tiesler, Carla M T
    Jula, Antti
    Navarro, Pau
    Wright, Alan F
    Polasek, Ozren
    Wilson, James F
    Rudan, Igor
    Salomaa, Veikko
    Heinrich, Joachim
    Campbell, Harry
    Price, Jacqueline F
    Karlsson, Magnus
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bandinelli, Stefania
    Frayling, Timothy M
    Hartman, Catharina A
    Sørensen, Thorkild I A
    Kritchevsky, Stephen B
    Langdahl, Bente Lomholt
    Eriksson, Johan G
    Florez, Jose C
    Spector, Tim D
    Lehtimäki, Terho
    Kuh, Diana
    Humphries, Steve E
    Cooper, Cyrus
    Ohlsson, Claes
    März, Winfried
    de Borst, Martin H
    Kumari, Meena
    Kivimaki, Mika
    Wang, Thomas J
    Power, Chris
    Brenner, Hermann
    Grimnes, Guri
    van der Harst, Pim
    Snieder, Harold
    Hingorani, Aroon D
    Pilz, Stefan
    Whittaker, John C
    Järvelin, Marjo-Riitta
    Hyppönen, Elina
    Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study2014Ingår i: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 2, nr 9, s. 719-729Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.

    METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium.

    FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002).

    INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

  • 129.
    Wadelius, Mia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Chen, L.Y.
    Downes, K.
    Ghori, J.
    Hunt, S.
    Eriksson, Niclas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Wallerman, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wadelius, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Bentley, D.
    Deloukas, P.
    Common VKORC1 and GGCX polymorphisms associated with warfarin dose2005Ingår i: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 5, nr 4, s. 262-70Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We report a novel combination of factors that explains almost 60% of variable response to warfarin. Warfarin is a widely used anticoagulant, which acts through interference with vitamin K epoxide reductase that is encoded by VKORC1. In the next step of the vitamin K cycle, gamma-glutamyl carboxylase encoded by GGCX uses reduced vitamin K to activate clotting factors. We genotyped 201 warfarin-treated patients for common polymorphisms in VKORC1 and GGCX. All the five VKORC1 single-nucleotide polymorphisms covary significantly with warfarin dose, and explain 29-30% of variance in dose. Thus, VKORC1 has a larger impact than cytochrome P450 2C9, which explains 12% of variance in dose. In addition, one GGCX SNP showed a small but significant effect on warfarin dose. Incorrect dosage, especially during the initial phase of treatment, carries a high risk of either severe bleeding or failure to prevent thromboembolism. Genotype-based dose predictions may in future enable personalised drug treatment from the start of warfarin therapy.The Pharmacogenomics Journal advance online publication, 10 May 2005; doi:10.1038/sj.tpj.6500313.

  • 130.
    Wadelius, Mia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Sörlin, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Wallerman, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Karlsson, Jacob
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Yue, Q.Y.
    Magnusson, P.K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Wadelius, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors2004Ingår i: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 4, nr 1, s. 40-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The required dose of the oral anticoagulant warfarin varies greatly, and overdosing often leads to bleeding. Warfarin is metabolised by cytochrome P450 enzymes CYP2C9, CYP1A2 and CYP3A. The target cell level of warfarin may be dependent on the efflux pump P-glycoprotein, encoded by the adenosine triphosphate-binding cassette gene ABCB1 (multidrug resistance gene 1). Genetic variability in CYP2C9, CYP3A5 and ABCB1 was analysed in 201 stable warfarin-treated patients using solid-phase minisequencing, pyrosequencing and SNaPshot. CYP2C9 variants, age, weight, concurrent drug treatment and indication for treatment significantly influenced warfarin dosing in these patients, explaining 29% of the variation in dose. CYP3A5 did not affect warfarin dosing. An ABCB1 haplotype containing the exon 26 3435T variant was over-represented among low-dose patients. Thirty-six patients with serious bleeding complications had higher prothrombin time international normalised ratios than 189 warfarin-treated patients without serious bleeding, but there were no significant differences in CYP2C9, CYP3A5 or ABCB1 genotypes and allelic variants.

  • 131.
    Wagner, Helene
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Pedersen, Nancy L
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Genetic influence on bone phenotypes and body composition: a Swedish twin study2013Ingår i: Journal of Bone and Mineral Metabolism, ISSN 0914-8779, E-ISSN 1435-5604, Vol. 31, nr 6, s. 681-689Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bone mineral density (BMD), bone size and bone turnover are independent determinants of fractures in elderly. Earlier twin studies of these phenotypes have revealed high heritability for BMD and bone area, and more moderate heritability for bone turnover markers. No previous Scandinavian study has evaluated the genetic and environmental contribution to the variance of these phenotypes, despite the fact that Scandinavian countries have the highest incidence of osteoporotic fractures worldwide. Participants were selected from the Swedish Twin Registry. All intact like-sexed twin pairs born in 1965 or earlier and living in the county of Uppsala were invited to participate. A total of 102 twin pairs (45 monozygotic and 57 dizygotic) accepted the invitation to participate. All twins underwent measurement of BMD and bone area using dual-energy X-ray absorptiometry. Hip geometry was also calculated. Markers for bone formation (osteocalcin) and bone resorption (CrossLaps) were measured in serum. We observed a substantial heritability for BMD at the lumbar spine (0.85; 95 % CI 0.54-0.90), the femoral neck (0.75; 95 % CI 0.62-0.83), and the proximal femur (0.84; 95 % CI 0.74-0.90). The values for bone area were approximately similar to those for BMD. Bone turnover markers had a slightly lower genetic influence with a value of 0.69 (0.53-0.80) for osteocalcin and 0.58 (95 % CI 0.33-0.75) for CrossLaps. As a comparison, the heritabilities of body height and weight were 0.95 and 0.82, respectively. The high heritability on bone phenotypes among Swedish middle-aged and older men and women should encourage further work on the identification of specific genetic pathways. Continuing research in this area could reveal the mechanisms behind the strong genetic susceptibility of bone-related phenotypes.

  • 132.
    Wagner, Helene
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Pedersen, Nancy
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Heritable and environmental factors in the causation of clinical vertebral fractures2012Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 90, nr 6, s. 458-464Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Vertebral fractures are common osteoporotic fractures, and their incidence is greater in Scandinavia than in other European regions. Vertebral fractures are strongly associated with low bone mineral density, which has a predominant genetic etiology. The heritability of radiological vertebral deformities has been estimated in one recent family study. The objective of our study was to determine the genetic liability to clinical vertebral fractures and to what extent individual-specific environmental factors can explain the variance of these fractures. Participants were ascertained from the Swedish Twin Registry. Twin pairs born 1896-1944 formed the study base, a total of 33,432 subjects. Vertebral fractures after the age of 50 years were identified in the National Patient Register ( = 1,037) or by self-report ( = 35). The age-adjusted heritability for all vertebral fractures was 0.17 (95 % CI 0.00-0.40). Restricting the fracture cases to low-energy causes of injury, the heritability was 0.24 (95 % CI 0.00-0.47). Individual-specific environmental influences were found to explain one-third of the variance in vertebral fracture occurrence before the age of 70 years (0.33, 95 % CI 0.16-0.56), whereas they explained most of the variance among those 80 years of age or older (0.83, 95 % CI 0.61-1.00). We conclude that the occurrence of clinical vertebral fractures is largely explained by environmental influences and not by genetic factors. Individual-specific environmental influences such as lifestyle become more important with increasing age, and it is of importance to identify those environmental factors that cause more fracture cases in Scandinavia than in other European settings.

  • 133.
    Warensjö, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Gedeborg, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study2011Ingår i: BMJ (British edition), ISSN 1756-1833, Vol. 342, s. d1473-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    To investigate associations between long term dietary intake of calcium and risk of fracture of any type, hip fractures, and osteoporosis.

    DESIGN:

    A longitudinal and prospective cohort study, based on the Swedish Mammography Cohort, including a subcohort, the Swedish Mammography Cohort Clinical.

    SETTING:

    A population based cohort in Sweden established in 1987.

    PARTICIPANTS:

    61,433 women (born between 1914 and 1948) were followed up for 19 years. 5022 of these women participated in the subcohort.

    MAIN OUTCOME MEASURES:

    Primary outcome measures were incident fractures of any type and hip fractures, which were identified from registry data. Secondary outcome was osteoporosis diagnosed by dual energy x ray absorptiometry in the subcohort. Diet was assessed by repeated food frequency questionnaires.

    RESULTS:

    During follow-up, 14,738 women (24%) experienced a first fracture of any type and among them 3871 (6%) a first hip fracture. Of the 5022 women in the subcohort, 1012 (20%) were measured as osteoporotic. The risk patterns with dietary calcium were non-linear. The crude rate of a first fracture of any type was 17.2/1000 person years at risk in the lowest quintile of calcium intake, and 14.0/1000 person years at risk in the third quintile, corresponding to a multivariable adjusted hazard ratio of 1.18 (95% confidence interval 1.12 to 1.25). The hazard ratio for a first hip fracture was 1.29 (1.17 to 1.43) and the odds ratio for osteoporosis was 1.47 (1.09 to 2.00). With a low vitamin D intake, the rate of fracture in the first calcium quintile was more pronounced. The highest quintile of calcium intake did not further reduce the risk of fractures of any type, or of osteoporosis, but was associated with a higher rate of hip fracture, hazard ratio 1.19 (1.06 to 1.32).

    CONCLUSION:

    Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis.

  • 134.
    Warensjö Lemming, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi. Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol.
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Long-term a posteriori dietary patterns and risk of hip fractures in a cohort of women2017Ingår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 32, nr 7, s. 605-616Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dietary pattern analysis is a useful tool to study the importance of food components in the context of a diet and how they relate to health and disease. The association between dietary patterns and fractures is at present uncertain. We aimed to study associations between dietary patterns and risk of hip fracture in the Swedish Mammography Cohort, including 56,736 women (median baseline age 52 years). Diet data was collected in food frequency questionnaires at two investigations and dietary patterns were defined by principal component analysis using 31 food groups. Information on hip fractures was collected from the Swedish National Patient Register. Multivariable adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated in Cox proportional hazards regression analysis. The two patterns identified-the healthy and Western/convenience dietary patterns-were time-updated and analysed. During a median follow-up time of 25.5 years, 4997 women experienced a hip fracture. Hip fracture rate was 31% lower in the highest compared to the lowest quartile of the healthy dietary pattern [HR (95% CI) 0.69 (0.64; 0.75)]. In contrast, women in the highest compared to the lowest quartile of the Western/convenience dietary pattern had a 50% higher [HR (95% CI) 1.50 (1.38; 1.62)] hip fracture rate. Further, in each stratum of a Western/convenience dietary pattern a higher adherence to a healthy dietary pattern was associated with less hip fractures. The present results suggest that a varied healthy diet may be beneficial for the prevention of fragility fractures in women.

  • 135. Wedrén, Sara
    et al.
    Lovmar, Lovisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Humphreys, Keith
    Magnusson, Cecilia
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Syvänen, Ann-Christine
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Landegren, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Fermer, Maria Lagerström
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Stiger, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Persson, Ingemar
    Baron, John
    Weiderpass, Elisabete
    Oestrogen receptor alpha gene haplotype and postmenopausal breast cancer risk: a case control study2004Ingår i: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 6, nr 4, s. R437-49Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    INTRODUCTION: Oestrogen receptor alpha, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor alpha gene (ESR1) are associated with breast cancer risk. METHODS: We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TAn, 1514 cases and 1514 controls; c.454-397C --> T, 1557 cases and 1512 controls; c.454-351A --> G, 1556 cases and 1512 controls; c.729C --> T, 1562 cases and 1513 controls; c.975C --> G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data. RESULTS: There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A --> G or c.454-397C --> T and c.975C --> G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A --> G and c.975C --> G haplotype entailed an OR of 1.19 (95% CI 1.06-1.33) and two copies with an OR of 1.42 (95% CI 1.15-1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C --> T and c.975C --> G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant. CONCLUSION: We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women.

  • 136. Wedrén, Sara
    et al.
    Magnusson, Cecilia
    Humphreys, Keith
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kindmark, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Stiger, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Branting, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Persson, Ingemar
    Baron, John
    Weiderpass, Elisabete
    Associations between androgen and Vitamin D receptor microsatellites and postmenopausal breast cancer2007Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 16, nr 9, s. 1775-1783Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We investigated the association between polymorphism in the androgen receptor (AR) and vitamin D receptor (VDR) genes and breast cancer risk in a large population-based case-control study of genetically homogenous Swedish women. We successfully determined both AR CAG(n) and VDR A(n) genotype in 1,502 women with invasive breast cancer and in 1,510 control women. We did not find any associations between AR or VDR microsatellite lengths and breast cancer when we used a priori determined cutoffs (</=21 or >/=22 repeats for AR and </=18 or >/=19 for VDR) to define long and short alleles. There was statistically significant interaction between VDR genotype and parity, such that women with two short alleles had a halved risk for breast cancer, irrespective of parity, compared with nulliparous women with two long alleles. Homozygosity for the long VDR allele was associated with a more advanced clinical stage at diagnosis. In exploratory analyses, we determined cutoffs based on visual inspection of distributions of allele lengths among cases and controls and found that women carrying two alleles with <20 AR CAG(n) repeats had an increased risk for breast cancer, odds ratio of 1.67 (95% confidence interval, 1.17-2.38), compared with those with two alleles with >/=20 repeats. Women carrying two VDR alleles with <21 A(n) were also at an increased risk, odds ratio of 1.26 (95% confidence interval, 1.04-1.51). Our data do not support major roles for AR or VDR polymorphism as breast cancer risk factors. However, we did find an interaction between VDR genotype and parity that remains to be corroborated.

  • 137.
    Zillikens, M. Carola
    et al.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands..
    Demissie, Serkalem
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Hsu, Yi-Hsiang
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA..
    Yerges-Armstrong, Laura M.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA..
    Chou, Wen-Chi
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst, Cambridge, MA 02142 USA..
    Stolk, Lisette
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands..
    Livshits, Gregory
    Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-6997801 Tel Aviv, Israel.;Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London WC2R 2LS, England..
    Broer, Linda
    Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Johnson, Toby
    Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Inst Social & Prevent Med, Ctr Hosp Univ CHUV, CH-1010 Lausanne, Switzerland..
    Koller, Daniel L.
    Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA..
    Kutalik, Zoltyn
    Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Inst Social & Prevent Med, Ctr Hosp Univ CHUV, CH-1010 Lausanne, Switzerland..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England..
    Malkin, Ida
    Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-6997801 Tel Aviv, Israel..
    Ried, Janina S.
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany..
    Smith, Albert V.
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland..
    Thorleifsson, Gudmar
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England..
    Zhang, Weihua
    Imperial Coll, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England.;Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England..
    Aghdassi, Ali
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, D-17489 Greifswald, Germany..
    Akesson, Kristina
    Lund Univ, Dept Clin Sci, S-22362 Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, S-20502 Malmo, Sweden..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Baier, Leslie J.
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Saffron Walden CB10 1SA, Essex, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Inst Met Sci, Cambridge CB2 OQQ, England.;Univ Cambridge, Addenbrookes Hosp, Inst Met Sci, Metab Res Labs, Cambridge CB2 OQQ, England..
    Bennett, David A.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA..
    Bertram, Lars
    Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Inst Neurogenet & Expt & Integrat Gen, D-23562 Lubeck, Germany.;Imperial Coll London, Fac Med, Sch Publ Hlth, London W6 8RP, England..
    Biffar, Rainer
    Ernst Moritz Arndt Univ Greifswald, Ctr Oral Hlth, Dept Prosthet Dent Gerodontol & Biomat, D-17489 Greifswald, Germany..
    Bochud, Murielle
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Inst Social & Prevent Med, Ctr Hosp Univ CHUV, CH-1010 Lausanne, Switzerland..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Borecki, Ingrid B.
    Washington Univ, Div Stat Gen, Dept Genet, Sch Med, St Louis, MO 63110 USA.;Washington Univ, Div Biostat, Sch Med, St Louis, MO 63110 USA..
    Buchman, Aron S.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA..
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Obanda, Natalia Campos
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands..
    Cauley, Jane A.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA..
    Cawthon, Peggy M.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    Cederberg, Henna
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Chen, Zhao
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85714 USA..
    Cho, Nam H.
    Ajou Univ, Sch Med, Dept Prevent Med, Suwon 16499, South Korea..
    Choi, Hyung Jin
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 03080, South Korea.;Chungbuk Natl Univ Hosp, Dept Internal Med, Cheongju, South Korea..
    Claussnitzer, Melina
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst, Cambridge, MA 02142 USA.;MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.;Tech Univ Munich, Inst Human Genet, MRI, D-81675 Munich, Germany.;Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA..
    Collins, Francis
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Cummings, Steven R.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    De Jager, Philip L.
    Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiatr Genom, Boston, MA 02115 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Demuth, Ilja
    Charite, Res Grp Geriatr, Berlin Aging Study 2, D-13353 Berlin, Germany.;Charite, Inst Med & Human Genet, D-13353 Berlin, Germany..
    Dhonukshe-Rutten, Rosalie A. M.
    Wageningen Univ, Dept Human Nutr, POB 17, NL-6700 AA Wageningen, Netherlands..
    Diatchenko, Luda
    McGill Univ, Alan Edwards Ctr Res Pain, Montreal H3A 0G1, PQ, Canada.;Univ N Carolina, Sch Dent, Reg Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA..
    Eiriksdottir, Gudny
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland..
    Enneman, Anke W.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands..
    Erdos, Mike
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Eriksson, Johan G.
    Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki 00014, Finland.;Univ Helsinki, Cent Hosp, Unity Gen Practice, Helsinki 00014, Finland.;Folkhalsan Res Ctr, Helsinki 00250, Finland.;Vasa Cent Hosp, Vaasa 65130, Finland.;Nat Inst Hlth & Welf, Helsinki 00271, Finland..
    Eriksson, Joel
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Estrada, Karol
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Evans, Daniel S.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    Feitosa, Mary F.
    Washington Univ, Div Stat Gen, Dept Genet, Sch Med, St Louis, MO 63110 USA..
    Fu, Mao
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA..
    Garcia, Melissa
    Natl Inst Aging, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Gieger, Christian
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany..
    Girke, Thomas
    Univ Calif Riverside, Inst Integrat Genome Biol, Dept Bot & Plant Sci, Riverside, CA 92521 USA.;Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA..
    Glazer, Nicole L.
    Boston Univ, Sch Med & Publ Hlth, Dept Med, Boston, MA 02118 USA.;Boston Univ, Sch Med & Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA..
    Grallert, Harald
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, CCG Type Diabet 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, CCG Nutrigen & Type Diabet 2, D-85764 Neuherberg, Germany..
    Grewal, Jagvir
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England..
    Han, Bok-Ghee
    Osong Hlth Technol Adm Complex, Ctr Genome Sci, Natl Inst Hlth, Chungcheongbuk Do 28159, South Korea..
    Hanson, Robert L.
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Hayward, Caroline
    Univ Edinburgh, IGMM, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Hofman, Albert
    NCHA, NCI, NL-2593 Leiden, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Hoffman, Eric P.
    SUNY Binghamton, Dept Pharmaceut Sci, Binghamton, NY 13902 USA..
    Homuth, Georg
    Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, D-17487 Greifswald, Germany..
    Hsueh, Wen-Chi
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Hubal, Monica J.
    George Washington Univ, Dept Exercise & Nutr Sci, Washington, DC 20052 USA.;Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20052 USA..
    Hubbard, Alan
    Univ Calif Berkeley, Div Biostat, Sch Publ Hlth, Berkeley, CA 94720 USA..
    Huffman, Kim M.
    Duke Univ, Sch Med, Div Rheumatol, Dept Med,Duke Mol Physiol Inst, Durham, NC 27710 USA..
    Husted, Lise B.
    Aarhus Univ Hosp, Endocrinol & Internal Med, DK-8000 Aarhus, Denmark..
    Illig, Thomas
    Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Hannover Med Sch, Dept Human Genet, D-30625 Hannover, Germany.;Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Ittermann, Till
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17489 Greifswald, Germany..
    Jansson, John-Olov
    Univ Gothenburg, Dept Physiol, Inst Neurosci & Physiol, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Jordan, Joanne M.
    Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC 27517 USA..
    Jula, Antti
    Nat Inst Hlth & Welf, Helsinki 00271, Finland..
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci & Orthopaed, Skane Univ Hosp SUS, S-22362 Malmo, Sweden..
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England..
    Kilpainen, Tuomas O.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England.;Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, DK-2100 Copenhagen, Denmark.;Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA..
    Klopp, Norman
    Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany..
    Kloth, Jacqueline S. L.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands..
    Koistinen, Heikki A.
    Univ Helsinki, Dept Med, Helsinki 00029, Finland.;Helsinki Univ Cent Hosp, Helsinki 00029, Finland.;Univ Helsinki, Abdominal Ctr, Endocrinol, Helsinki 00029, Finland.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland.;Minerva Fdn, Helsinki 00290, Finland..
    Kraus, William E.
    Duke Univ, Sch Med, Div Cardiol, Dept Med,Duke Mol Physiol Inst, Durham, NC 27710 USA..
    Kritchevsky, Stephen
    Sticht Ctr Aging, Wake Forest Sch Med, Winston Salem, NC 27157 USA..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Lahti, Jari
    Univ Helsinki, Inst Behav Sci, FI-00014 Helsinki, Finland..
    Lang, Thomas
    Univ Calif San Francisco, San Francisco, CA 94143 USA..
    Langdahl, Bente L.
    Aarhus Univ Hosp, Endocrinol & Internal Med, DK-8000 Aarhus, Denmark..
    Launer, Lenore J.
    Natl Inst Aging, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Lee, Jong-Young
    Osong Hlth Technol Adm Complex, Ctr Genome Sci, Natl Inst Hlth, Chungcheongbuk Do 28159, South Korea..
    Lerch, Markus M.
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, D-17489 Greifswald, Germany..
    Lewis, Joshua R.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.;Univ Sydney, Ctr Kidney Res, Sch Publ Hlth, Sydney, NSW 2006, Australia..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi. Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden..
    Lindgren, Cecilia
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Liu, Yongmei
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27517 USA..
    Liu, Tian
    Max Planck Inst Mol Genet, D-14195 Berlin, Germany.;Max Planck Inst Human Dev, D-14195 Berlin, Germany..
    Liu, Youfang
    Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC 27517 USA..
    Ljunggren, Östen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrinologi och mineralmetabolism.
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Luben, Robert N.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England..
    Maixner, William
    Univ N Carolina, Sch Dent, Reg Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA..
    McGuigan, Fiona E.
    Lund Univ, Dept Clin Sci, S-22362 Malmo, Sweden..
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, MRI, D-81675 Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, D-85764 Neuherberg, Germany..
    Melhus, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Melov, Simon
    Buck Inst Res Aging, Novato, CA 94945 USA.;Univ Southern Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90089 USA..
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mitchell, Braxton D.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.;Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Inst Tradit Med, Liverpool L69 3BX, Merseyside, England..
    Mosekilde, Leif
    Aarhus Univ Hosp, Endocrinol & Internal Med, DK-8000 Aarhus, Denmark..
    Newman, Anne
    Univ Pittsburgh, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA..
    Nielson, Carrie M.
    Oregon Hlth & Sci Univ, Portland, OR 97239 USA..
    O'Connell, Jeffrey R.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA..
    Oostra, Ben A.
    Erasmus MC, Dept Clin Genet, NL-300 CA Rotterdam, Netherlands.;Ctr Med Syst Biol & Netherlands Consortium Hlth A, RC-2300 Leiden, Netherlands..
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Portland, OR 97239 USA..
    Palotie, Aarno
    Harvard Med Sch, Boston, MA 02115 USA.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Univ Helsinki, Dept Med Genet, FI-00014 Helsinki, Finland.;Univ Cent Hosp, FI-00014 Helsinki, Finland..
    Parker, Stephan
    Univ Michigan, Human Genet & Computat Med & Bioinformat, Ann Arbor, MI 48109 USA..
    Peacock, Munro
    Indiana Univ, Dept Med, Sch Med, Indianapolis, IN 46202 USA..
    Perola, Markus
    Nat Inst Hlth & Welf, Helsinki 00271, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Univ Helsinki, Diabet & Obes Res Program, FI-00014 Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Peters, Annette
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany..
    Polasek, Ozren
    Univ Split, Fac Med, Dept Publ Hlth, Split 21000, Croatia..
    Prince, Richard L.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.;Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA 6009, Australia..
    Raikkonen, Katri
    Univ Helsinki, Inst Behav Sci, FI-00014 Helsinki, Finland..
    Ralston, Stuart H.
    Western Gen Hosp, Mol Med Ctr, MRC Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Ripatti, Samuli
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Univ Helsinki, Hjelt Inst, Helsinki, Finland.;Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England..
    Robbins, John A.
    Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Salomaa, Veikko
    Nat Inst Hlth & Welf, Helsinki 00271, Finland..
    Satterfield, Suzanne
    Univ Tennessee, Dept Prevent Med, Hlth Sci Ctr, Memphis, TN 38163 USA..
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Inst Genom & Multiscale Biol, New York, NY 10029 USA..
    Schipf, Sabine
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17489 Greifswald, Germany..
    Scott, Laura
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Sehmi, Joban
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England..
    Shen, Jian
    Oregon Hlth & Sci Univ, Portland, OR 97239 USA..
    Shin, Chan Soo
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 03080, South Korea..
    Sigurdsson, Gunnar
    Natl Univ Hosp Iceland, Landspitali, Dept Endocrinol & Metab, IS-101 Reykjavik, Iceland..
    Smith, Shad
    Duke Univ, Med Ctr, Ctr Translat Pain Med, Dept Anesthesiol, Durham, NC 27110 USA..
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England..
    Stancakova, Alena
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Steinhagen-Thiessen, Elisabeth
    Charite, Res Grp Geriatr, Berlin Aging Study 2, D-13353 Berlin, Germany..
    Streeten, Elizabeth A.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.;Vet Adm Med Ctr, GRECC, Baltimore, MD 21201 USA..
    Styrkarsdottir, Unnur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Swart, Karin M. A.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, BT-1081 Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst, BT-1081 Amsterdam, Netherlands..
    Tan, Sian-Tsung
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England..
    Tarnopolsky, Mark A.
    McMaster Univ, Med Ctr, Dept Med, Hamilton, ON L8N 3Z5, Canada..
    Thompson, Patricia
    Stony Brook Sch Med, Dept Pathol, Stony Brook, NY 11794 USA..
    Thomson, Cynthia A.
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85714 USA..
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Tikkanen, Emmi
    Nat Inst Hlth & Welf, Helsinki 00271, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Western Gen Hosp, Mol Med Ctr, MRC Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Tranah, Gregory J.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    Tuomilehto, Jaakko
    Vasa Cent Hosp, Vaasa 65130, Finland.;Danube Univ Krems, Dept Neurosci & Prevent Med, A-3500 Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah 12589, Saudi Arabia.;Dasman Diabet Inst, Dasman 15462, Kuwait..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, BT-1081 Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst, BT-1081 Amsterdam, Netherlands..
    Verma, Arjun
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England..
    Vollenweider, Peter
    CHU Vaudois, Dept Med & Internal Med, CH-1011 Lausanne, Switzerland..
    Voelzke, Henry
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17489 Greifswald, Germany..
    Wactawski-Wende, Jean
    SUNY Buffalo, Univ Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14214 USA..
    Walker, Mark
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England..
    Weedon, Michael N.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter EX1 2LU, Devon, England..
    Welch, Ryan
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Wichman, H. -Erich
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, D-81377 Munich, Germany.;Tech Univ, Inst Med Stat & Epidemiol, D-81675 Munich, Germany..
    Widen, Elisabeth
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland..
    Williams, Frances M. K.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London WC2R 2LS, England..
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Edinburgh, IGMM, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Wright, Nicole C.
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA..
    Xie, Weijia
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter EX1 2LU, Devon, England..
    Yu, Lei
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA..
    Zhou, Yanhua
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Chambers, John C.
    Imperial Coll, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England.;Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Royal Brompton & Harefield NHS Fdn Trust, NIHR Cardiovasc Biomed Res Unit, London SW3 6NP, England.;Imperial Coll, London SW3 6NP, England.;Imperial Coll Healthcare NHS Trust, London W2 1NY, England..
    Doring, Angela
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, D-85764 Neuherberg, Germany..
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands.;Ctr Med Syst Biol & Netherlands Consortium Hlth A, RC-2300 Leiden, Netherlands..
    Econs, Michael J.
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA.;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA..
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland..
    Kooner, Jaspal S.
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England.;Imperial Coll Healthcare NHS Trust, London W2 1NY, England..
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med Hlth Serv, Seattle, WA 98101 USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London WC2R 2LS, England..
    Stefansson, Kari
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England..
    Ossowski, Vicky
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Waterworth, Dawn
    GlaxoSmithKline, Med Genet, Philadelphia, PA 19112 USA..
    Loos, Ruth J. F.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Inst Child Hlth & Dev, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA..
    Karasik, David
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Bar Ilan Univ, Fac Med Galilee, IL-1311502 Safed, Israel..
    Harris, Tamara B.
    Natl Inst Aging, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Kiel, Douglas P.
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA..
    Large meta-analysis of genome-wide association studies identifies five loci for lean body mass2017Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, artikel-id 80Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.

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