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  • 201. Morris, Andrew P
    et al.
    Le, Thu H
    Wu, Haojia
    Akbarov, Artur
    van der Most, Peter J
    Hemani, Gibran
    Smith, George Davey
    Mahajan, Anubha
    Gaulton, Kyle J
    Nadkarni, Girish N
    Valladares-Salgado, Adan
    Wacher-Rodarte, Niels
    Mychaleckyj, Josyf C
    Dueker, Nicole D
    Guo, Xiuqing
    Hai, Yang
    Haessler, Jeffrey
    Kamatani, Yoichiro
    Stilp, Adrienne M
    Zhu, Gu
    Cook, James P
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Blanton, Susan H
    de Borst, Martin H
    Bottinger, Erwin P
    Buchanan, Thomas A
    Cechova, Sylvia
    Charchar, Fadi J
    Chu, Pei-Lun
    Damman, Jeffrey
    Eales, James
    Gharavi, Ali G
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Heath, Andrew C
    Ipp, Eli
    Kiryluk, Krzysztof
    Kramer, Holly J
    Kubo, Michiaki
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lindgren, Cecilia M
    Lu, Yingchang
    Madden, Pamela A F
    Montgomery, Grant W
    Papanicolaou, George J
    Raffel, Leslie J
    Sacco, Ralph L
    Sanchez, Elena
    Stark, Holger
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Taylor, Kent D
    Xiang, Anny H
    Zivkovic, Aleksandra
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, Stanford Univ, Stanford Cardiovasc Inst, Stanford, USA; Stanford Univ, Stanford Diabet Res Ctr, Stanford, USA.
    Martin, Nicholas G
    Whitfield, John B
    Cai, Jianwen
    Laurie, Cathy C
    Okada, Yukinori
    Matsuda, Koichi
    Kooperberg, Charles
    Chen, Yii-Der Ida
    Rundek, Tatjana
    Rich, Stephen S
    Loos, Ruth J F
    Parra, Esteban J
    Cruz, Miguel
    Rotter, Jerome I
    Snieder, Harold
    Tomaszewski, Maciej
    Humphreys, Benjamin D
    Franceschini, Nora
    Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies2019Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, nr 1, artikel-id 29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

  • 202.
    Mubanga, Mwenya
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Dog Ownership and Cardiovascular Disease2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The relationship between pet ownership and human health has been studied extensively; however, the effect of dog ownership on human health has had conflicting results. The overall aim of this research project was to investigate the impact of dog ownership, and the death of the dog, on human cardiovascular health and all-cause mortality.

    Study I was a population-based study investigating the association between dog ownership with the risk of cardiovascular disease (CVD) and death. Of 3,432,153 individuals included, dog ownership (13.1%) was associated with a lower risk of CVD- and all-cause death by 23% and 20%, respectively. In single-person households, there was an inverse association between dog ownership and incident CVD, as well as a stronger inverse association with CVD-death and all-cause death.

    Study II was a population-based study investigating the association between dog ownership and initiation of treatment for cardiovascular risk factors in 2,026,865 adults. Dog ownership (14.6%) was associated with a slightly elevated risk of initiating treatment (2%) for hypertension and dyslipidaemia, but not for diabetes mellitus. However, some evidence for residual confounding was found.

    Study III investigated the risk of death after hospitalization for a first-ever acute myocardial infarction (n=181,696) or first-ever ischemic stroke (n=157,617) in two population-based cohorts. Dog ownership was associated with a 20% to 24% lower risk of all-cause mortality and CVD-death, respectively.

    In Study I-III, ownership of hunting breed dogs was associated with the lowest risk of the outcomes, while owning dogs of mixed pedigree was associated with worse cardiovascular health.

    Study IV found evidence of an increased risk of CVD after the loss of a life-insured pet (dog or cat; n=147,251) during the first week, 3-6 months after and 6-12 months after pet-loss.

    This thesis has used the Swedish population and health registers to investigate the relationship between various aspects of dog ownership and cardiovascular risk. By using defined, quantifiable end-points and robust statistical methods, this project has made an important contribution to the body of research underlying the positive relationship between dog ownership and cardiovascular health, paving the way for further research into causal mechanisms.

    Delarbeten
    1. Dog ownership and the risk of cardiovascular disease and death: a nationwide cohort study
    Öppna denna publikation i ny flik eller fönster >>Dog ownership and the risk of cardiovascular disease and death: a nationwide cohort study
    Visa övriga...
    2017 (Engelska)Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, nr 1, artikel-id 15821Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Dogs may be beneficial in reducing cardiovascular risk in their owners by providing social support and motivation for physical activity. We aimed to investigate the association of dog ownership with incident cardiovascular disease (CVD) and death in a register-based prospective nation-wide cohort (n = 3,432,153) with up to 12 years of follow-up. Self-reported health and lifestyle habits were available for 34,202 participants in the Swedish Twin Register. Time-to-event analyses with time-updated covariates were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). In single- and multiple-person households, dog ownership (13.1%) was associated with lower risk of death, HR 0.67 (95% CI, 0.65-0.69) and 0.89 (0.87-0.91), respectively; and CVD death, HR 0.64 (0.59-0.70), and 0.85 (0.81-0.90), respectively. In single-person households, dog ownership was inversely associated with cardiovascular outcomes (HR composite CVD 0.92, 95% CI, 0.89-0.94). Ownership of hunting breed dogs was associated with lowest risk of CVD. Further analysis in the Twin Register could not replicate the reduced risk of CVD or death but also gave no indication of confounding by disability, comorbidities or lifestyle factors. In conclusion, dog ownership appears to be associated with lower risk of CVD in single-person households and lower mortality in the general population.

    Nationell ämneskategori
    Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi Kardiologi
    Identifikatorer
    urn:nbn:se:uu:diva-334415 (URN)10.1038/s41598-017-16118-6 (DOI)000415658600066 ()29150678 (PubMedID)
    Forskningsfinansiär
    Forskningsrådet Formas, 2013-1673
    Tillgänglig från: 2017-11-23 Skapad: 2017-11-23 Senast uppdaterad: 2018-08-24Bibliografiskt granskad
    2. Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study
    Öppna denna publikation i ny flik eller fönster >>Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study
    Visa övriga...
    2019 (Engelska)Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, artikel-id 23447Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objective To study the association between dog ownership and cardiovascular risk factors.

    Design A nationwide register–based cohort study and a cross-sectional study in a subset.

    Setting A cohort of 2 026 865 participants was identified from the Register of the Total Population and linked to national registers for information on dog ownership, prescribed medication, hospital admissions, education level, income and country of birth. Participants were followed from 1 October, 2006, to the end of the study on 31 December, 2012, assessing medication for a cardiovascular risk factor, emigration and death. Cross-sectional associations were further assessed in 10 110 individuals from the TwinGene study with additional adjustment for professional level, employment status, Charlson comorbidity index, disability and tobacco use.

    Participants All Swedish residents aged 45–80 years on 1 October, 2006.

    Main outcome measures Initiation of medication for hypertension, dyslipidaemia and diabetes mellitus.

    Results After adjustment for confounders, the results indicated slightly higher likelihood of initiating antihypertensive (HR, 1.02; 95% CI, 1.01 to 1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01 to 1.04) in dog owners than in non-owners, particularly among those aged 45–60 years and in those owning mixed breed or companion/toy breed dogs. No association of dog ownership with initiation of treatment for diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95 to 1.01). Sensitivity analyses in the TwinGene cohort indicated confounding of the association between dog ownership and prevalent treatment for hypertension, dyslipidaemia and diabetes mellitus, respectively, from factors not available in the national cohort, such as employment status and non cardiovascularchronic disease status.

    Conclusions In this large cohort study, dog ownership was associated with a minimally higher risk of initiation of treatment for hypertension and dyslipidaemia implying that the previously reported lower risk of cardiovascular mortality among dog owners in this cohort is not explained by reduced hypertension and dyslipidaemia. These observations may suffer from residual confounding despite access to multiple important covariates, and future studies may add valuable information.

    Nyckelord
    cardiovascular risk, hypertension, dog ownership, diabetes, registers
    Nationell ämneskategori
    Kardiologi Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi
    Identifikatorer
    urn:nbn:se:uu:diva-357625 (URN)10.1136/bmjopen-2018-023447 (DOI)000471144900063 ()30850401 (PubMedID)
    Forskningsfinansiär
    Vetenskapsrådet, 2017-00641Forskningsrådet Formas, 2013-1673Göran Gustafssons stiftelse för naturvetenskaplig och medicinsk forskning (KVA)
    Tillgänglig från: 2018-08-19 Skapad: 2018-08-19 Senast uppdaterad: 2019-12-18Bibliografiskt granskad
    3. Dog ownership and mortality after a major cardiovascular event – a register-based prospective study
    Öppna denna publikation i ny flik eller fönster >>Dog ownership and mortality after a major cardiovascular event – a register-based prospective study
    Visa övriga...
    (Engelska)Ingår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685Artikel i tidskrift (Refereegranskat) Submitted
    Nyckelord
    mortality, dog ownership, major cardiovascular event
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Forskningsämne
    Epidemiologi
    Identifikatorer
    urn:nbn:se:uu:diva-357626 (URN)
    Tillgänglig från: 2018-08-19 Skapad: 2018-08-19 Senast uppdaterad: 2018-08-21
    4. The impact of death of a pet on major acute cardiovascular risk in the owner: a register-based cohort study
    Öppna denna publikation i ny flik eller fönster >>The impact of death of a pet on major acute cardiovascular risk in the owner: a register-based cohort study
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-357627 (URN)
    Tillgänglig från: 2018-08-19 Skapad: 2018-08-19 Senast uppdaterad: 2018-08-21
  • 203.
    Mubanga, Mwenya
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA..
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Dog ownership and mortality after a major cardiovascular event – a register-based prospective studyIngår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685Artikel i tidskrift (Refereegranskat)
  • 204.
    Mubanga, Mwenya
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Egenvall, Agneta
    Swedish Univ Agr Sci, Div Ruminant Med & Vet Epidemiol, Dept Clin Sci, Uppsala, Sweden.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Dog Ownership and Survival After a Major Cardiovascular Event: A Register-Based Prospective Study2019Ingår i: Circulation. Cardiovascular Quality and Outcomes, ISSN 1941-7713, E-ISSN 1941-7705, Vol. 12, nr 10, artikel-id e005342Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dog ownership is associated with increased physical activity levels and increased social support, both of which could improve the outcome after a major cardiovascular event. Dog ownership may be particularly important in single-occupancy households where ownership provides substitutive companionship and motivation for physical activity.

    Methods and Results: We used the Swedish National Patient Register to identify all patients aged 40 to 85 presenting with an acute myocardial infarction (n=181 696; 5.7% dog ownership) or ischemic stroke (n=154 617; 4.8% dog ownership) between January 1, 2001 and December 31, 2012. Individual information was linked across registers for cause of death, sociodemographic, and dog ownership data. We evaluated all-cause mortality and risk of recurrent hospitalization for the same cause until December 31, 2012. Models were adjusted for socioeconomic, health, and demographic factors at study inclusion such as age, marital status, the presence of children in the home, area of residence, and income, as well as all registered comorbidities and hospitalization for cardiovascular disease in the past 5 years. Dog owners had a lower risk of death after hospitalization for acute myocardial infarction during the full follow-up period of 804 137 person-years, with an adjusted hazard ratio (HR) of 0.67 (95% CI, 0.61 to 0.75) for those who lived alone, and HR of 0.85 (95% CI, 0.80 to 0.90) for those living with a partner or a child. Similarly, after an ischemic stroke, dog owners were at lower risk of death during the full follow-up of 638 219 person-years adjusted HR of 0.73 (95% CI, 0.66 to 0.80) for those who lived alone and HR of 0.88 (95% CI, 0.83 to 0.93) for those living with a partner or a child. We further found an association of dog ownership with reduced risk of hospitalization for recurrent myocardial infarction (HR, 0.93; 95% CI, 0.87 to 0.99).

    Conclusions: We found evidence of an association of dog ownership with a better outcome after a major cardiovascular event. Although our models are adjusted for many potential confounders, there are also unmeasured confounders such as smoking that prevent us from drawing conclusions regarding a possible causal effect.

  • 205.
    Mubanga, Mwenya
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk epidemiologi.
    Magnusson, Patrik K
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA..
    Fall, Tove
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study2019Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, artikel-id 23447Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To study the association between dog ownership and cardiovascular risk factors.

    Design A nationwide register–based cohort study and a cross-sectional study in a subset.

    Setting A cohort of 2 026 865 participants was identified from the Register of the Total Population and linked to national registers for information on dog ownership, prescribed medication, hospital admissions, education level, income and country of birth. Participants were followed from 1 October, 2006, to the end of the study on 31 December, 2012, assessing medication for a cardiovascular risk factor, emigration and death. Cross-sectional associations were further assessed in 10 110 individuals from the TwinGene study with additional adjustment for professional level, employment status, Charlson comorbidity index, disability and tobacco use.

    Participants All Swedish residents aged 45–80 years on 1 October, 2006.

    Main outcome measures Initiation of medication for hypertension, dyslipidaemia and diabetes mellitus.

    Results After adjustment for confounders, the results indicated slightly higher likelihood of initiating antihypertensive (HR, 1.02; 95% CI, 1.01 to 1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01 to 1.04) in dog owners than in non-owners, particularly among those aged 45–60 years and in those owning mixed breed or companion/toy breed dogs. No association of dog ownership with initiation of treatment for diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95 to 1.01). Sensitivity analyses in the TwinGene cohort indicated confounding of the association between dog ownership and prevalent treatment for hypertension, dyslipidaemia and diabetes mellitus, respectively, from factors not available in the national cohort, such as employment status and non cardiovascularchronic disease status.

    Conclusions In this large cohort study, dog ownership was associated with a minimally higher risk of initiation of treatment for hypertension and dyslipidaemia implying that the previously reported lower risk of cardiovascular mortality among dog owners in this cohort is not explained by reduced hypertension and dyslipidaemia. These observations may suffer from residual confounding despite access to multiple important covariates, and future studies may add valuable information.

  • 206.
    Mubanga, Mwenya
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Byberg, Liisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nowak, Christoph
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Magnusson, Patrik K
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    Fall, Tove
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Dog ownership and the risk of cardiovascular disease and death: a nationwide cohort study2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, nr 1, artikel-id 15821Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dogs may be beneficial in reducing cardiovascular risk in their owners by providing social support and motivation for physical activity. We aimed to investigate the association of dog ownership with incident cardiovascular disease (CVD) and death in a register-based prospective nation-wide cohort (n = 3,432,153) with up to 12 years of follow-up. Self-reported health and lifestyle habits were available for 34,202 participants in the Swedish Twin Register. Time-to-event analyses with time-updated covariates were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). In single- and multiple-person households, dog ownership (13.1%) was associated with lower risk of death, HR 0.67 (95% CI, 0.65-0.69) and 0.89 (0.87-0.91), respectively; and CVD death, HR 0.64 (0.59-0.70), and 0.85 (0.81-0.90), respectively. In single-person households, dog ownership was inversely associated with cardiovascular outcomes (HR composite CVD 0.92, 95% CI, 0.89-0.94). Ownership of hunting breed dogs was associated with lowest risk of CVD. Further analysis in the Twin Register could not replicate the reduced risk of CVD or death but also gave no indication of confounding by disability, comorbidities or lifestyle factors. In conclusion, dog ownership appears to be associated with lower risk of CVD in single-person households and lower mortality in the general population.

  • 207.
    Mubanga, Mwenya
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Mariosa, Daniela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA..
    Fang, Fang
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm. Sweden..
    Byberg, Liisa
    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.
    The impact of death of a pet on major acute cardiovascular risk in the owner: a register-based cohort studyManuskript (preprint) (Övrigt vetenskapligt)
  • 208. Murray, Christopher J L
    et al.
    Ortblad, Katrina F
    Guinovart, Caterina
    Lim, Stephen S
    Wolock, Timothy M
    Roberts, D Allen
    Dansereau, Emily A
    Graetz, Nicholas
    Barber, Ryan M
    Brown, Jonathan C
    Wang, Haidong
    Duber, Herbert C
    Naghavi, Mohsen
    Dicker, Daniel
    Dandona, Lalit
    Salomon, Joshua A
    Heuton, Kyle R
    Foreman, Kyle
    Phillips, David E
    Fleming, Thomas D
    Flaxman, Abraham D
    Phillips, Bryan K
    Johnson, Elizabeth K
    Coggeshall, Megan S
    Abd-Allah, Foad
    Abera, Semaw Ferede
    Abraham, Jerry P
    Abubakar, Ibrahim
    Abu-Raddad, Laith J
    Abu-Rmeileh, Niveen Me
    Achoki, Tom
    Adeyemo, Austine Olufemi
    Adou, Arsène Kouablan
    Adsuar, José C
    Agardh, Emilie Elisabet
    Akena, Dickens
    Al Kahbouri, Mazin J
    Alasfoor, Deena
    Albittar, Mohammed I
    Alcalá-Cerra, Gabriel
    Alegretti, Miguel Angel
    Alemu, Zewdie Aderaw
    Alfonso-Cristancho, Rafael
    Alhabib, Samia
    Ali, Raghib
    Alla, Francois
    Allen, Peter J
    Alsharif, Ubai
    Alvarez, Elena
    Alvis-Guzman, Nelson
    Amankwaa, Adansi A
    Amare, Azmeraw T
    Amini, Hassan
    Ammar, Walid
    Anderson, Benjamin O
    Antonio, Carl Abelardo T
    Anwari, Palwasha
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Arsenijevic, Valentina S Arsic
    Artaman, Ali
    Asghar, Rana J
    Assadi, Reza
    Atkins, Lydia S
    Badawi, Alaa
    Balakrishnan, Kalpana
    Banerjee, Amitava
    Basu, Sanjay
    Beardsley, Justin
    Bekele, Tolesa
    Bell, Michelle L
    Bernabe, Eduardo
    Beyene, Tariku Jibat
    Bhala, Neeraj
    Bhalla, Ashish
    Bhutta, Zulfiqar A
    Abdulhak, Aref Bin
    Binagwaho, Agnes
    Blore, Jed D
    Bose, Dipan
    Brainin, Michael
    Breitborde, Nicholas
    Castañeda-Orjuela, Carlos A
    Catalá-López, Ferrán
    Chadha, Vineet K
    Chang, Jung-Chen
    Chiang, Peggy Pei-Chia
    Chuang, Ting-Wu
    Colomar, Mercedes
    Cooper, Leslie Trumbull
    Cooper, Cyrus
    Courville, Karen J
    Cowie, Benjamin C
    Criqui, Michael H
    Dandona, Rakhi
    Dayama, Anand
    De Leo, Diego
    Degenhardt, Louisa
    Del Pozo-Cruz, Borja
    Deribe, Kebede
    Des Jarlais, Don C
    Dessalegn, Muluken
    Dharmaratne, Samath D
    Dilmen, Uğur
    Ding, Eric L
    Driscoll, Tim R
    Durrani, Adnan M
    Ellenbogen, Richard G
    Ermakov, Sergey Petrovich
    Esteghamati, Alireza
    Faraon, Emerito Jose A
    Farzadfar, Farshad
    Fereshtehnejad, Seyed-Mohammad
    Fijabi, Daniel Obadare
    Forouzanfar, Mohammad H
    Fra Paleo, Urbano
    Gaffikin, Lynne
    Gamkrelidze, Amiran
    Gankpé, Fortuné Gbètoho
    Geleijnse, Johanna M
    Gessner, Bradford D
    Gibney, Katherine B
    Ginawi, Ibrahim Abdelmageem Mohamed
    Glaser, Elizabeth L
    Gona, Philimon
    Goto, Atsushi
    Gouda, Hebe N
    Gugnani, Harish Chander
    Gupta, Rajeev
    Gupta, Rahul
    Hafezi-Nejad, Nima
    Hamadeh, Randah Ribhi
    Hammami, Mouhanad
    Hankey, Graeme J
    Harb, Hilda L
    Haro, Josep Maria
    Havmoeller, Rasmus
    Hay, Simon I
    Hedayati, Mohammad T
    Pi, Ileana B Heredia
    Hoek, Hans W
    Hornberger, John C
    Hosgood, H Dean
    Hotez, Peter J
    Hoy, Damian G
    Huang, John J
    Iburg, Kim M
    Idrisov, Bulat T
    Innos, Kaire
    Jacobsen, Kathryn H
    Jeemon, Panniyammakal
    Jensen, Paul N
    Jha, Vivekanand
    Jiang, Guohong
    Jonas, Jost B
    Juel, Knud
    Kan, Haidong
    Kankindi, Ida
    Karam, Nadim E
    Karch, André
    Karema, Corine Kakizi
    Kaul, Anil
    Kawakami, Norito
    Kazi, Dhruv S
    Kemp, Andrew H
    Kengne, Andre Pascal
    Keren, Andre
    Kereselidze, Maia
    Khader, Yousef Saleh
    Khalifa, Shams Eldin Ali Hassan
    Khan, Ejaz Ahmed
    Khang, Young-Ho
    Khonelidze, Irma
    Kinfu, Yohannes
    Kinge, Jonas M
    Knibbs, Luke
    Kokubo, Yoshihiro
    Kosen, S
    Defo, Barthelemy Kuate
    Kulkarni, Veena S
    Kulkarni, Chanda
    Kumar, Kaushalendra
    Kumar, Ravi B
    Kumar, G Anil
    Kwan, Gene F
    Lai, Taavi
    Balaji, Arjun Lakshmana
    Lam, Hilton
    Lan, Qing
    Lansingh, Van C
    Larson, Heidi J
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lee, Jong-Tae
    Leigh, James
    Leinsalu, Mall
    Leung, Ricky
    Li, Yichong
    Li, Yongmei
    De Lima, Graça Maria Ferreira
    Lin, Hsien-Ho
    Lipshultz, Steven E
    Liu, Shiwei
    Liu, Yang
    Lloyd, Belinda K
    Lotufo, Paulo A
    Machado, Vasco Manuel Pedro
    Maclachlan, Jennifer H
    Magis-Rodriguez, Carlos
    Majdan, Marek
    Mapoma, Christopher Chabila
    Marcenes, Wagner
    Marzan, Melvin Barrientos
    Masci, Joseph R
    Mashal, Mohammad Taufiq
    Mason-Jones, Amanda J
    Mayosi, Bongani M
    Mazorodze, Tasara T
    Mckay, Abigail Cecilia
    Meaney, Peter A
    Mehndiratta, Man Mohan
    Mejia-Rodriguez, Fabiola
    Melaku, Yohannes Adama
    Memish, Ziad A
    Mendoza, Walter
    Miller, Ted R
    Mills, Edward J
    Mohammad, Karzan Abdulmuhsin
    Mokdad, Ali H
    Mola, Glen Liddell
    Monasta, Lorenzo
    Montico, Marcella
    Moore, Ami R
    Mori, Rintaro
    Moturi, Wilkister Nyaora
    Mukaigawara, Mitsuru
    Murthy, Kinnari S
    Naheed, Aliya
    Naidoo, Kovin S
    Naldi, Luigi
    Nangia, Vinay
    Narayan, K M Venkat
    Nash, Denis
    Nejjari, Chakib
    Nelson, Robert G
    Neupane, Sudan Prasad
    Newton, Charles R
    Ng, Marie
    Nisar, Muhammad Imran
    Nolte, Sandra
    Norheim, Ole F
    Nowaseb, Vincent
    Nyakarahuka, Luke
    Oh, In-Hwan
    Ohkubo, Takayoshi
    Olusanya, Bolajoko O
    Omer, Saad B
    Opio, John Nelson
    Orisakwe, Orish Ebere
    Pandian, Jeyaraj D
    Papachristou, Christina
    Caicedo, Angel J Paternina
    Patten, Scott B
    Paul, Vinod K
    Pavlin, Boris Igor
    Pearce, Neil
    Pereira, David M
    Pervaiz, Aslam
    Pesudovs, Konrad
    Petzold, Max
    Pourmalek, Farshad
    Qato, Dima
    Quezada, Amado D
    Quistberg, D Alex
    Rafay, Anwar
    Rahimi, Kazem
    Rahimi-Movaghar, Vafa
    Rahman, Sajjad Ur
    Raju, Murugesan
    Rana, Saleem M
    Razavi, Homie
    Reilly, Robert Quentin
    Remuzzi, Giuseppe
    Richardus, Jan Hendrik
    Ronfani, Luca
    Roy, Nobhojit
    Sabin, Nsanzimana
    Saeedi, Mohammad Yahya
    Sahraian, Mohammad Ali
    Samonte, Genesis May J
    Sawhney, Monika
    Schneider, Ione J C
    Schwebel, David C
    Seedat, Soraya
    Sepanlou, Sadaf G
    Servan-Mori, Edson E
    Sheikhbahaei, Sara
    Shibuya, Kenji
    Shin, Hwashin Hyun
    Shiue, Ivy
    Shivakoti, Rupak
    Sigfusdottir, Inga Dora
    Silberberg, Donald H
    Silva, Andrea P
    Simard, Edgar P
    Singh, Jasvinder A
    Skirbekk, Vegard
    Sliwa, Karen
    Soneji, Samir
    Soshnikov, Sergey S
    Sreeramareddy, Chandrashekhar T
    Stathopoulou, Vasiliki Kalliopi
    Stroumpoulis, Konstantinos
    Swaminathan, Soumya
    Sykes, Bryan L
    Tabb, Karen M
    Talongwa, Roberto Tchio
    Tenkorang, Eric Yeboah
    Terkawi, Abdullah Sulieman
    Thomson, Alan J
    Thorne-Lyman, Andrew L
    Towbin, Jeffrey A
    Traebert, Jefferson
    Tran, Bach X
    Dimbuene, Zacharie Tsala
    Tsilimbaris, Miltiadis
    Uchendu, Uche S
    Ukwaja, Kingsley N
    Vallely, Andrew J
    Vasankari, Tommi J
    Venketasubramanian, N
    Violante, Francesco S
    Vlassov, Vasiliy Victorovich
    Waller, Stephen
    Wallin, Mitchell T
    Wang, Linhong
    Wang, Sharon Xiaorong
    Wang, Yanping
    Weichenthal, Scott
    Weiderpass, Elisabete
    Weintraub, Robert G
    Westerman, Ronny
    White, Richard A
    Wilkinson, James D
    Williams, Thomas Neil
    Woldeyohannes, Solomon Meseret
    Wong, John Q
    Xu, Gelin
    Yang, Yang C
    Yano, Yuichiro
    Yip, Paul
    Yonemoto, Naohiro
    Yoon, Seok-Jun
    Younis, Mustafa
    Yu, Chuanhua
    Jin, Kim Yun
    El Sayed Zaki, Maysaa
    Zhao, Yong
    Zheng, Yingfeng
    Zhou, Maigeng
    Zhu, Jun
    Zou, Xiao Nong
    Lopez, Alan D
    Vos, Theo
    Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 20132014Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, nr 9947, s. 1005-1070Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

    METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

    FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.

    INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

  • 209. Nead, Kevin T.
    et al.
    Li, Aihua
    Wehner, Mackenzie R.
    Neupane, Binod
    Gustafsson, Stefan
    Butterworth, Adam
    Engert, James C.
    Davis, A. Darlene
    Hegele, Robert A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Miller, Ruby
    den Hoed, Marcel
    Khaw, Kay-Tee
    Kilpelaeinen, Tuomas O.
    Wareham, Nick
    Edwards, Todd L.
    Hallmans, Goeran
    Varga, Tibor V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kardia, Sharon L. R.
    Smith, Jennifer A.
    Zhao, Wei
    Faul, Jessica D.
    Weir, David
    Mi, Jie
    Xi, Bo
    Quinteros, Samuel Canizales
    Cooper, Cyrus
    Sayer, Avan Aihie
    Jameson, Karen
    Grontved, Anders
    Fornage, Myriam
    Sidney, Stephen
    Hanis, Craig L.
    Highland, Heather M.
    Haering, Hans-Ulrich
    Heni, Martin
    Lasky-Su, Jessica
    Weiss, Scott T.
    Gerhard, Glenn S.
    Still, Christopher
    Melka, Melkaey M.
    Pausova, Zdenka
    Paus, Tomas
    Grant, Struan F. A.
    Hakonarson, Hakon
    Price, R. Arlen
    Wang, Kai
    Scherag, Andre
    Hebebrand, Johannes
    Hinney, Anke
    Franks, Paul W.
    Frayling, Timothy M.
    McCarthy, Mark I.
    Hirschhorn, Joel N.
    Loos, Ruth J.
    Ingelsson, Erik
    Gerstein, Hertzel C.
    Yusuf, Salim
    Beyene, Joseph
    Anand, Sonia S.
    Meyre, David
    Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals2015Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, nr 12, s. 3582-3594Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) a parts per thousand yen 40 kg/m(2)], but their contribution to common obesity (BMI a parts per thousand yen 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 x 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 x 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (beta = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (beta = 0.02, 95% CI 0.00-0.03; P = 5.57 x 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.

  • 210. Nelson, C. P.
    et al.
    Hamby, S. E.
    Saleheen, D.
    Hopewell, J. C.
    Zeng, L.
    Assimes, T. L.
    Kanoni, S.
    Willenborg, C.
    Burgess, S.
    Amouyel, P.
    Anand, S.
    Blankenberg, S.
    Boehm, B. O.
    Clarke, R. J.
    Collins, R.
    Dedoussis, G.
    Farrall, M.
    Franks, P. W.
    Groop, L.
    Hall, A. S.
    Hamsten, A.
    Hengstenberg, C.
    Hovingh, G. Kees
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kathiresan, S.
    Kee, F.
    Koenig, I. R.
    Kooner, J.
    Lehtimaeki, T.
    Maerz, W.
    McPherson, R.
    Metspalu, A.
    Nieminen, M. S.
    O'Donnell, C. J.
    Palmer, C. N. A.
    Peters, A.
    Perola, M.
    Reilly, M. P.
    Ripatti, S.
    Roberts, R.
    Salomaa, V.
    Shah, S. H.
    Schreiber, S.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Thorsteinsdottir, U.
    Veronesi, G.
    Wareham, N.
    Willer, C. J.
    Zalloua, P. A.
    Erdmann, J.
    Deloukas, P.
    Watkins, H.
    Schunkert, H.
    Danesh, J.
    Thompson, J. R.
    Samani, N. J.
    Genetically Determined Height and Coronary Artery Disease2015Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 372, nr 17, s. 1608-1618Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quar-tile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. CONCLUSIONS There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association.

  • 211.
    Nerpin, Elisabet
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna-Medicinsk vetenskap.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Andrén, Bertil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Jobs, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna Medicinsk vetenskap.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Högskolan Dalarna Medicinsk vetenskap.
    The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly2014Ingår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, nr 11, s. 2069-2074Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) > 40% and with pre-specified sub-group analyses in individuals with a GFR > 60 mL/min/m(2). Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR > 60 mL/min/m(2). Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease.

  • 212.
    Nettleton, Jennifer A.
    et al.
    Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA..
    Follis, Jack L.
    Univ St Thomas, Dept Math, Houston, TX 77006 USA..
    Ngwa, Julius S.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Smith, Caren E.
    Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA.;Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
    Ahmad, Shafqat
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden..
    Tanaka, Toshiko
    NIA, Clin Res Branch, Baltimore, MD 21224 USA..
    Wojczynski, Mary K.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Voortman, Trudy
    Erasmus MC, Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands..
    Lemaitre, Rozenn N.
    Univ Washington, Dept Med, Seattle, WA 98195 USA..
    Kristiansson, Kati
    Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki 00290, Finland..
    Nuotio, Marja-Liisa
    Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki 00290, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland..
    Houston, Denise K.
    Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA..
    Perala, Mia-Maria
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00290, Finland..
    Qi, Qibin
    Harvard Univ, Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Albert Einstein Coll Med, Dept Epidemiol & Publ Hlth, Bronx, NY 10467 USA..
    Sonestedt, Emily
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Manichaikul, Ani
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.;Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Ganna, Andrea
    Karolinska Inst, Dept Med Epidemiol & Biostatist, Stockholm, Sweden..
    Mikkila, Vera
    Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    North, Kari E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.;Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA..
    Siscovick, David S.
    New York Acad Med, New York, NY USA..
    Harald, Kennet
    THL Natl Inst Hlth & Welf, Helsinki 00300, Finland..
    Mckeown, Nicola M.
    Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA.;Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
    Johansson, Ingegerd
    Umea Univ, Dept Odontol, Umea, Sweden..
    Rissanen, Harri
    THL Natl Inst Hlth & Welf, Helsinki 00300, Finland..
    Liu, Yongmei
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA..
    Lahti, Jari
    Univ Helsinki, Inst Behav Sci, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Hu, Frank B.
    Harvard Univ, Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA..
    Bandinelli, Stefania
    ASF, Geriatr Unit, Florence, Italy..
    Rukh, Gull
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Rich, Stephen
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA..
    Booij, Lisanne
    NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Dmitriou, Maria
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Ax, Erika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Raitakari, Olli
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.;Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland..
    Mukamal, Kenneth
    Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00290, Finland..
    Hallmans, Goran
    Umea Univ, Dept Publ Hlth & Clin Med Nutr Res, Umea, Sweden..
    Jula, Antti
    THL Natl Inst Hlth & Welf, Helsinki 00300, Finland..
    Ericson, Ulrika
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Jacobs, David R., Jr.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Van Rooij, Frank J. A.
    Erasmus MC, Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands..
    Deloukas, Panos
    Wellcome Trust Sanger Inst, Hinxton, Cambs, England..
    Sjögren, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Kahonen, Mika
    Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland.;Tampere Univ Hosp, Tampere, Finland..
    Djousse, Luc
    Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA 02115 USA.;Boston VA Healthcare Syst, Boston, MA USA..
    Perola, Markus
    Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki 00290, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Metab Dis Grp, Hinxton, Cambs, England.;Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England..
    Hofman, Albert
    Erasmus MC, Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands..
    Stirrups, Kathleen
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Viikari, Jorma
    Univ Turku, Dept Med, Turku, Finland.;Turku Univ Hosp, Div Med, FIN-20520 Turku, Finland..
    Uitterlinden, Andre G.
    NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Kalafati, Ioanna P.
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Franco, Oscar H.
    Erasmus MC, Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.;NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands..
    Mozaffarian, Dariush
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
    Salomaa, Veikko
    THL Natl Inst Hlth & Welf, Helsinki 00300, Finland..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Knekt, Paul
    THL Natl Inst Hlth & Welf, Helsinki 00300, Finland..
    Kritchevsky, Stephen B.
    Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA..
    Eriksson, Johan G.
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki 00290, Finland.;Univ Helsinki, Inst Clin Med, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland..
    Dedoussis, George V.
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Qi, Lu
    Harvard Univ, Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA..
    Ferrucci, Luigi
    NIA, Clin Res Branch, Baltimore, MD 21224 USA..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Zillikens, M. Carola
    NCHA, Netherlands Genom Initiat NGI Sponsored Netherlan, Leiden, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lehtimaki, Terho
    Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland.;Univ Tampere, Sch Med, FIN-33101 Tampere, Finland..
    Renstrom, Frida
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Cupples, L. Adrienne
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Franks, Paul W.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.;Harvard Univ, Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Gene x dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry2015Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, nr 16, s. 4728-4738Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.

  • 213.
    Ng, Esther
    et al.
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin. Uppsala Univ, Dept Med Sci Occupat & Environm Med, S-75185 Uppsala, Sweden..
    Lindgren, Cecilia
    Harvard Univ, Inst Technol, Broad Inst Massachusetts, Cambridge, MA 02142 USA..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Mahajan, Anubha
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Morris, Andrew
    Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Genome-wide association study of toxic metals and trace elements reveals novel associations2015Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, nr 16, s. 4739-4745Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The accumulation of toxic metals in the human body is influenced by exposure and mechanisms involved in metabolism, some of which may be under genetic control. This is the first genome-wide association study to investigate variants associated with whole blood levels of a range of toxic metals. Eleven toxic metals and trace elements (aluminium, cadmium, cobalt, copper, chromium, mercury, manganese, molybdenum, nickel, lead and zinc) were assayed in a cohort of 949 individuals using mass spectrometry. DNA samples were genotyped on the Infinium Omni Express bead microarray and imputed up to reference panels from the 1000 Genomes Project. Analyses revealed two regions associated with manganese level at genome-wide significance, mapping to 4q24 and 1q41. The lead single nucleotide polymorphism(SNP) in the 4q24 locus was rs13107325 (P-value = 5.1 x 10(-11), beta = -0.77), located in an exon of SLC39A8, which encodes a protein involved in manganese and zinc transport. The lead SNP in the 1q41 locus is rs1776029 (P-value = 2.2 x 10(-14), beta = -0.46). The SNP lies within the intronic region of SLC30A10, another transporter protein. Among other metals, the loci 6q14.1 and 3q26.32 were associated with cadmium and mercury levels (P = 1.4x10(-10), beta = -1.2 and P = 1.8x10(-9), beta = -1.8, respectively). Whole blood measurements of toxicmetals are associated with genetic variants in metal transporter genes and others. This is relevant in inferring metabolic pathways of metals and identifying subsets of individuals who may be more susceptible to metal toxicity.

  • 214. Ng, Esther
    et al.
    Salihovic, Samira
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lind, P. Monica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Mahajan, Anubha
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lindgren, Cecilia M
    van Bavel, Bert
    Morris, Andrew P
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Genome-wide association study of plasma levels of polychlorinated biphenyls disclose an association with the CYP2B6 gene in a population-based sample2015Ingår i: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 140, s. 95-101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Polychlorinated biphenyls (PCBs) are a group of man-made environmental pollutants which accumulate in humans with adverse health effects. To date, very little effort has been devoted to the study of the metabolism of PCBs on a genome-wide level.

    OBJECTIVES: Here, we conducted a genome-wide association study (GWAS) to identify genomic regions involved in the metabolism of PCBs.

    METHODS: Plasma levels of 16 PCBs ascertained in a cohort of elderly individuals from Sweden (n=1016) were measured using gas chromatography-high resolution mass spectrophotometry (GC-HRMS). DNA samples were genotyped on the Infinium Omni Express bead microarray, and imputed up to reference panels from the 1000 Genomes Project. Association testing was performed in a linear regression framework under an additive model.

    RESULTS: Plasma levels of PCB-99 demonstrated genome-wide significant association with single nucleotide polymorphisms (SNPs) mapping to chromosome 19q13.2. The SNP with the strongest association was rs8109848 (p=3.7×10(-13)), mapping to an intronic region of CYP2B6. Moreover, when all PCBs were conditioned on PCB-99, further signals were revealed for PCBs -74, -105 and -118, mapping to the same genomic region. The lead SNPs were rs8109848 (p=3.8×10(-12)) for PCB-118, rs4802104 (p=1.4×10(-9)) for PCB-74 and rs4803413 (p=2.5×10(-9)) for PCB-105, all of which map to CYP2B6.

    CONCLUSIONS: In our study, we found plasma levels of four lower-chlorinated PCBs to be significantly associated with the genetic region mapping to the CYP2B6 locus. These findings show that CYP2B6 is of importance for the metabolism of PCBs in humans, and may help to identify individuals who may be susceptible to PCB toxicity.

  • 215.
    Nielsen, Jonas B.
    et al.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Fritsche, Lars G.
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Zhou, Wei
    Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Teslovich, Tanya M.
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    Holmen, Oddgeir L.
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway.;St Olavs Univ Hosp, Dept Cardiol, N-7030 Trondheim, Norway..
    Gustafsson, Stefan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    Gabrielsen, Maiken E.
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Schmidt, Ellen M.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Beaumont, Robin
    Royal Devon & Exeter NHS Fdn Trust, Exeter EX2 5WD, Devon, England.;Univ Exeter, Exeter EX2 5WD, Devon, England..
    Wolford, Brooke N.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Lin, Maoxuan
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Brummett, Chad M.
    Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA..
    Preuss, Michael H.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Refsgaard, Lena
    Univ Copenhagen, Rigshosp, Dept Cardiol, Lab Mol Cardiol, DK-2100 Copenhagen, Denmark..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth Dev Inst, New York, NY 10029 USA..
    Graham, Sarah E.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Surakka, Ida
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Chu, Yunhan
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Skogholt, Anne Heidi
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Dalen, Havard
    St Olavs Univ Hosp, Dept Cardiol, N-7030 Trondheim, Norway.;Nord Trondelag Hosp Trust, Levanger Hosp, Dept Med, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Circulat & Med Imaging, N-7491 Trondheim, Norway..
    Boyle, Alan P.
    Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA..
    Oral, Hakan
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Herron, Todd J.
    Univ Michigan, Ctr Arrhythmia Res, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Kitzman, Jacob
    Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Jalife, Jose
    Univ Michigan, Ctr Arrhythmia Res, Dept Internal Med, Ann Arbor, MI 48109 USA.;Fdn Ctr Nacl Invest Cardiovasc, Madrid 28029, Spain..
    Svendsen, Jesper H.
    Univ Copenhagen, Rigshosp, Dept Cardiol, Lab Mol Cardiol, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen, Denmark..
    Olesen, Morten S.
    Univ Copenhagen, Rigshosp, Dept Cardiol, Lab Mol Cardiol, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Dept Biomed, DK-2200 Copenhagen, Denmark..
    Njolstad, Inger
    UiT Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway..
    Lochen, Maja-Lisa
    UiT Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway..
    Baras, Aris
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    Gottesman, Omri
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    Marcketta, Anthony
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    O'Dushlaine, Colm
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    Ritchie, Marylyn D.
    Geisinger Hlth Syst, Danville, PA 17822 USA..
    Wilsgaard, Tom
    UiT Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Frayling, Timothy M.
    Royal Devon & Exeter NHS Fdn Trust, Exeter EX2 5WD, Devon, England.;Univ Exeter, Exeter EX2 5WD, Devon, England..
    Boehnke, Michael
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Ingelsson, Erik
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Division of Cardiovascular Medicine, Depart- ment of Medicine, Stanford University School of Medicine, Stanford, USA.
    Carey, David J.
    Dewey, Frederick E.
    Regeneron Genet Ctr, Tarrytown, NY 10591 USA..
    Kang, Hyun M.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Abecasis, Goncalo R.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway.;Nord Trondelag Hosp Trust, Levanger Hosp, Dept Med, N-7600 Levanger, Norway..
    Willer, Cristen J.
    Univ Michigan, Div Cardiovasc Med, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7491 Trondheim, Norway.;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA..
    Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development2018Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 102, nr 1, s. 103-115Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10−18) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 × 10−11) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.

  • 216.
    Nikpay, Majid
    et al.
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Goel, Anuj
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Won, Hong-Hee
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA USA..
    Hall, Leanne M.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England..
    Willenborg, Christina
    Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.;DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Saleheen, Danish
    Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    Kyriakou, Theodosios
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Webb, Thomas R.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Zeng, Lingyao
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Dehghan, Abbas
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Alver, Maris
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia..
    Armasu, Sebastian M.
    Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA..
    Auro, Kirsi
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Bjonnes, Andrew
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA..
    Chen, Shufeng
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Franceschini, Nora
    Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA..
    Gieger, Christian
    DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Grace, Christopher
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Gustafsson, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Huang, Jie
    Wellcome Trust Sanger Inst, Hinxton, England..
    Hwang, Shih-Jen
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Kim, Yun Kyoung
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Vth Dept Med Nephrol Hypertensiol Endocrinol Diab, Mannheim, Germany..
    Lau, King Wai
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Lu, Xiangfeng
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Qu, Liming
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    Salfati, Elias
    Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Saxena, Richa
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA..
    Scholz, Markus
    Univ Leipzig, Fac Med, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany.;LIFE Res Ctr Civilizat Dis, Leipzig, Germany..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Tikkanen, Emmi
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Uitterlinden, Andre
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Yang, Xueli
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Zhang, Weihua
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England..
    Zhao, Wei
    Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA..
    de Andrade, Mariza
    Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA..
    de Vries, Paul S.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    van Zuydam, Natalie R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Dundee, Med Res Inst, Dundee, Scotland..
    Anand, Sonia S.
    McMaster Univ, Dept Med, Populat Hlth Res Inst, Hamilton Hlth Sci, Hamilton, ON, Canada..
    Bertram, Lars
    Univ Lubeck, Inst Neurogenet & Integrat, Platform Genome Analyt, Lubeck, Germany.;Univ Lubeck, Inst Expt Gen, Platform Genome Analyt, Lubeck, Germany.;Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Neuroepidemiol & Ageing Res Unit, London, England..
    Beutner, Frank
    LIFE Res Ctr Civilizat Dis, Leipzig, Germany.;Univ Leipzig, Heart Ctr Leipzig, Cardiol, D-04109 Leipzig, Germany..
    Dedoussis, George
    Harokopio Univ, Dept Dietet Nutr, Athens, Greece..
    Frossard, Philippe
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Gauguier, Dominique
    INSERM, Ctr Rech Cordeliers, UMRS 1138, Paris, France..
    Goodall, Alison H.
    Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.;Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England..
    Gottesman, Omri
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Haber, Marc
    Lebanese Amer Univ, Sch Med, Beirut, Lebanon..
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Huang, Jianfeng
    Peking Union Med Coll, Beijing 100021, Peoples R China.;Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, Hypertens Div, Beijing 100730, Peoples R China..
    Jalilzadeh, Shapour
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Kessler, Thorsten
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;Klinikum Rechts Der Isar, Munich, Germany..
    Koenig, Inke R.
    DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany.;Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany..
    Lannfelt, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Lieb, Wolfgang
    Univ Kiel, Inst Epidemiol, Kiel, Germany..
    Lind, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Broad Inst MIT & Harvard Univ, Cambridge, MA USA..
    Lokki, Marja-Liisa
    Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Mallick, Nadeem H.
    Punjab Inst Cardiol, Lahore, Pakistan..
    Mehra, Narinder
    All India Inst Med Sci, New Delhi, India..
    Meitinger, Thomas
    DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Humangenet, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany..
    Memon, Fazal-ur-Rehman
    Red Crescent Inst Cardiol, Hyderabad, Andhra Pradesh, Pakistan..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England..
    Nieminen, Markku S.
    Univ Helsinki, Cent Hosp, Dept Med, Dept Cardiol, Helsinki, Finland..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Munich, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Rallidis, Loukianos S.
    Univ Athens, Sch Med, Attikon Hosp, Dept Cardiol 2, GR-11527 Athens, Greece..
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan.;Red Crescent Inst Cardiol, Hyderabad, Andhra Pradesh, Pakistan..
    Samuel, Maria
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Shah, Svati H.
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA..
    Sinisalo, Juha
    Univ Helsinki, Cent Hosp, Dept Med, Dept Cardiol, Helsinki, Finland..
    Stirrups, Kathleen E.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Wang, Laiyuan
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China.;Natl Human Genome Ctr Beijing, Beijing, Peoples R China..
    Zaman, Khan S.
    Natl Inst Cardiovasc Dis, Karachi, Pakistan..
    Ardissino, Diego
    Univ Parma, Azienda Osped, Div Cardiol, I-43100 Parma, Italy.;Assoc Studio Trombosi Cardiol, Pavia, Italy..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Buring, Julie E.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    Chambers, John C.
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England.;Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Collins, Rory
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Cupples, L. Adrienne
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Danesh, John
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Demuth, Ilja
    Berlin Aging Study 2, Berlin, Germany.;Charite, Res Grp Geriatr, D-13353 Berlin, Germany.;Charite, Inst Med & Human Genet, D-13353 Berlin, Germany..
    Elosua, Roberto
    Inst Hosp Mar Invest Med IMIM, Grp Epidemiol & Genet Cardiovasc, Barcelona, Spain..
    Epstein, Stephen E.
    MedStar Washington Hosp Ctr, MedStar Heart & Vasc Inst, Washington, DC USA..
    Esko, Tonu
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Boston Childrens Hosp, Div Endocrinol & Basic & Translat Obes Res, Boston, MA USA.;Harvard Univ, Sch Med, Dept Genet, Boston, MA USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA..
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Franzosi, Maria Grazia
    IRCCS Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy..
    Granger, Christopher B.
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA..
    Gu, Dongfeng
    Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing 100730, Peoples R China.;Peking Union Med Coll, Beijing 100021, Peoples R China..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Hall, Alistair S.
    Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden..
    Harris, Tamara B.
    NIA, Lab Epidemiol Demog & Biometry, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Hazen, Stanley L.
    Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA..
    Hengstenberg, Christian
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Ingelsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Iribarren, Carlos
    Kaiser Permanente Div Res, Oakland, CA USA..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.;Interunivers Cardiol Inst Netherlands, Utrecht, Netherlands..
    Karhunen, Pekka J.
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Forens Med, FIN-33101 Tampere, Finland..
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea..
    Kooner, Jaspal S.
    Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Cardiovasc Sci, London, England..
    Kullo, Iftikhar J.
    Mayo Clin, Dept Med, Cardiovasc Dis, Rochester, MN USA..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Melander, Olle
    Lund Univ, Univ Hosp Malmo, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Vth Dept Med Nephrol Hypertensiol Endocrinol Diab, Mannheim, Germany.;Synlab Acad, Synlab Serv, Mannheim, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria..
    Palmer, Colin N.
    Univ Dundee, Med Res Inst, Dundee, Scotland..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Quertermous, Thomas
    Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA..
    Rader, Daniel J.
    Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA USA..
    Ripatti, Samuli
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Wellcome Trust Sanger Inst, Hinxton, England.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Roberts, Robert
    Univ Ottawa, Inst Heart, Ottawa, ON, Canada..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Sanghera, Dharambir K.
    Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Coll Med, Oklahoma City, OK 73190 USA.;Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA.;Oklahoma Ctr Neurosci, Oklahoma City, OK USA..
    Schwartz, Stephen M.
    Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98104 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Seedorf, Udo
    Univ Med Ctr Hamburg Eppendorf, Ctr Dent & Oral Med, Dept Prosthet Dent, Hamburg, Germany..
    Stewart, Alexandre F.
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Stott, David J.
    Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Thiery, Joachim
    LIFE Res Ctr Civilizat Dis, Leipzig, Germany.;Univ Hosp Leipzig, Fac Med, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany..
    Zalloua, Pierre A.
    Lebanese Amer Univ, Sch Med, Beirut, Lebanon.;Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA..
    O'Donnell, Christopher J.
    NHLBI, Framingham Heart Study, Framingham, MA USA.;NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.;Massachusetts Gen Hosp, Cardiol Div, Boston, MA 02114 USA..
    Reilly, Muredach P.
    Assimes, Themistocles L.
    Stanford Univ, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA..
    Thompson, John R.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Erdmann, Jeanette
    Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany.;DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany..
    Clarke, Robert
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England..
    Watkins, Hugh
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Kathiresan, Sekar
    Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA USA..
    McPherson, Ruth
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21413, Saudi Arabia..
    Schunkert, Heribert
    Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Farrall, Martin
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease2015Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 10, s. 1121-1130Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

  • 217.
    Nolte, Ilja M.
    et al.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Munoz, M. Loretto
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Tragante, Vinicius
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Amare, Azmeraw T.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands.;Univ Adelaide, Sch Med, Dept Epidemiol, Adelaide, SA 5005, Australia.;Bahir Dar Univ, Coll Med & Hlth Sci, Bahir Dar 6000, Ethiopia..
    Jansen, Rick
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci, Dept Psychiat,GGZ inGeest, Campus Amsterdam, NL-1081 BT Amsterdam, Netherlands..
    Vaez, Ahmad
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands.;Isfahan Univ Med Sci, Sch Med, Esfahan 8174673461, Iran..
    von der Heyde, Benedikt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Avery, Christy L.
    Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98104 USA..
    Dierckx, Bram
    Dept Child & Adolescent Psychiat, Dept Child & Adolescent Psychiat Psychol, POB 2060, NL-3000 CB Rotterdam, Netherlands.;Erasmus MC, Generat Study Grp R, POB 2060, NL-3000 CB0 Rotterdam, Netherlands..
    van Dongen, Jenny
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands..
    Gogarten, Stephanie M.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Goyette, Philippe
    Montreal Heart Inst, Montreal, PQ H1T IC8, Canada..
    Hernesniemi, Jussi
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland.;Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere 33521, Finland..
    Huikari, Ville
    Univ Oulu, Ctr Life Course Hlth Res, Oulu 90014, Finland..
    Hwang, Shih-Jen
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Jaju, Deepali
    Sultan Qaboos Univ Hosp, Dept Clin Physiol, Muscat 123, Oman..
    Kerr, Kathleen F.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Kluttig, Alexander
    Martin Luther Univ Halle Wittenberg, Inst Med Epidemiol Biostat & Informat, D-06097 Halle, Germany..
    Krijthe, Bouwe P.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands..
    Kumar, Jitender
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär epidemiologi.
    van der Laan, Sander W.
    Univ Med Ctr Utrecht, Dept Heart & Lung, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Maihofer, Adam X.
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.;VA San Diego Healthcare Syst, Ctr Stress & Mental Hlth CESAMH, San Diego, CA 92161 USA..
    Minassian, Arpi
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.;VA San Diego Healthcare Syst, Ctr Stress & Mental Hlth CESAMH, San Diego, CA 92161 USA..
    van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Dept Med, Univ Hosp Munich, D-80539 Munich, Germany.;Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Partner Site, D-80336 Munich, Germany..
    Nivard, Michel
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Salvi, Erika
    Univ Milan, Dept Hlth Sci, I-20122 Milan, Italy..
    Stewart, James D.
    Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.;Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27599 USA..
    Thayer, Julian F.
    Ohio State Univ, Dept Psychol, 1835 Neil Ave, Columbus, OH 43210 USA..
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Wong, Andrew
    UCL, MRC Unit Lifelong Hlth & Ageing, 33 Bedford Pl, London WC1B 5JU, England..
    Zabaneh, Delilah
    Kings Coll London, Inst Psychiat Psychol & Neurosci, De Crespigny Pk, London SE5 8AF, England.;UCL, Genet Inst, London WC1E 6BT, England..
    Zafarmand, Mohammad H.
    Univ Amsterdam, Acad Med Ctr, Dept Publ Hlth, NL-1105 AZ Amsterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Dept Obstet & Gynaecol, NL-1105 AZ Amsterdam, Netherlands..
    Abdellaoui, Abdel
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Albarwani, Sulayma
    Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Physiol, Muscat Al Khoudh 123, Oman..
    Albert, Christine
    Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA..
    Alonso, Alvaro
    Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA..
    Ashar, Foram
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA..
    Auvinen, Juha
    Univ Oulu, Ctr Life Course Hlth Res, Oulu 90014, Finland.;Oulu Univ Hosp, Unit Primary Hlth Care, Oulu 90220, Finland..
    Axelsson, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Baker, Dewleen G.
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.;VA San Diego Healthcare Syst, Ctr Stress & Mental Hlth CESAMH, San Diego, CA 92161 USA..
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Dept Genet, Ctr Mol Med, NL-3584 CX Utrecht, Netherlands.;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, NL-3584 CX Utrecht, Netherlands..
    Barcella, Matteo
    Univ Milan, Dept Hlth Sci, I-20122 Milan, Italy..
    Bayoumi, Riad
    Mohammed Bin Rashid Univ, Coll Med, Dubai Healthcare City, POB 505055, Dubai, U Arab Emirates..
    Bieringa, Rob J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Boomsma, Dorret
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Boucher, Gabrielle
    Montreal Heart Inst, Montreal, PQ H1T IC8, Canada..
    Britton, Annie R.
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England..
    Christophersen, Ingrid E.
    Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02114 USA.;MIT, Cambridge, MA 02114 USA.;Baerum Hosp, Vestre Viken Hosp Trust, Dept Med Res, N-1346 Rud, Norway..
    Dietrich, Andrea
    Univ Groningen, Univ Med Ctr Groningen, Dept Child & Adolescent Psychiat, POB 30001, NL-9700 RB Groningen, Netherlands..
    Ehret, George B.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA.;Geneva Univ Hosp, Dept Specialties Internal Med, Cardiol, CH-1211 Geneva, Switzerland..
    Ellinor, Patrick T.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02114 USA.;MIT, Cambridge, MA 02114 USA.;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Eskola, Markku
    Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere 33521, Finland.;Univ Tampere, Sch Med, Dept Cardiol, Tampere 33014, Finland..
    Felix, Janine F.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands..
    Floras, John S.
    Univ Toronto, Univ Hlth Network, Toronto, ON, Canada.;Univ Toronto, Mt Sinai Hosp, Div Cardiol, Dept Med, Toronto, ON, Canada.;Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON M5G 2C4, Canada..
    Franco, Oscar H.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands..
    Friberg, Peter
    Univ Gothenburg, Sahlgrenska Univ Hosp, Inst Med, Dept Mol & Clin Med, SE-41345 Gothenburg, Sweden..
    Gademan, Maaike G. J.
    Univ Amsterdam, Acad Med Ctr, Dept Publ Hlth, NL-1105 AZ Amsterdam, Netherlands..
    Geyer, Mark A.
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA..
    Giedraitis, Vilmantas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Dept Psychiat, POB 30001, NL-9700 RB Groningen, Netherlands..
    Hemerich, Daiane
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;Minist Educ Brazil, CAPES Fdn, BR-70040020 Brasilia, DF, Brazil..
    Hofman, Albert
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands..
    Hottenga, Jouke-Jan
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Huikuri, Heikki
    Oulu Univ Hosp, Med Res Ctr, Res Unit Internal Med, Oulu 90220, Finland.;Univ Oulu, SF-90220 Oulu, Finland..
    Hutri-Kahonen, Nina
    Tampere Univ Hosp, Dept Pediat, Tampere 33521, Finland.;Univ Tampere, Sch Med, Dept Pediat, Tampere 33014, Finland..
    Jouven, Xavier
    Paris Descartes Univ, INSERM, U970, F-75006 Paris, France..
    Junttila, Juhani
    Oulu Univ Hosp, Med Res Ctr, Res Unit Internal Med, Oulu 90220, Finland.;Univ Oulu, SF-90220 Oulu, Finland..
    Juonala, Markus
    Univ Turku, Dept Med, Turku 20520, Finland.;Turku Univ Hosp, Div Med, Turku 20521, Finland..
    Kiviniemi, Antti M.
    Oulu Univ Hosp, Med Res Ctr, Res Unit Internal Med, Oulu 90220, Finland.;Univ Oulu, SF-90220 Oulu, Finland..
    Kors, Jan A.
    Erasmus MC, Dept Med Informat, NL-3015 CE Rotterdam, Netherlands..
    Kumari, Meena
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.;Essex Univ, ISER, Colchester CO4 3SQ, Essex, England..
    Kuznetsova, Tatiana
    Univ Leuven, KU Leuven Dept Cardiovasc Sci, Studies Coordinating Ctr, Res Unit Hypertens & Cardiovasc Epidemiol, B-3000 Leuven, Belgium..
    Laurie, Cathy C.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Lefrandt, Joop D.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Vasc Med, POB 30001, NL-9700 RB Groningen, Netherlands..
    Li, Yong
    Univ Freiburg, Fac Med, Med Center, Div Genet Epidemiol,Inst Med Biometry & Stat, D-79110 Freiburg, Germany..
    Li, Yun
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.;Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.;Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA..
    Liao, Duanping
    Penn State Univ, Coll Med, Dept Publ Hlth Sci, Div Epidemiol, Hershey, PA 17033 USA..
    Limacher, Marian C.
    Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32611 USA..
    Lin, Henry J.
    Harbor UCLA Med Ctr, Dept Pediat, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Div Med Genet, Torrance, CA 90502 USA..
    Lindgren, Cecilia M.
    Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7BN, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Lubitz, Steven A.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02114 USA.;MIT, Cambridge, MA 02114 USA.;Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    McKnight, Barbara
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98104 USA.;Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.;Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA..
    zu Schwabedissen, Henriette Meyer
    Univ Basel, Dept Pharmaceut Sci, Biopharm, CH-4056 Basel, Switzerland..
    Milaneschi, Yuri
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci, Dept Psychiat,GGZ inGeest, Campus Amsterdam, NL-1081 BT Amsterdam, Netherlands..
    Mononen, Nina
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Nalls, Mike A.
    NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA..
    Navis, Gerjan
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Neijts, Melanie
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Nikus, Kjell
    Tampere Univ Hosp, Heart Hosp, Dept Cardiol, Tampere 33521, Finland.;Univ Tampere, Sch Med, Dept Cardiol, Tampere 33014, Finland..
    North, Kari E.
    Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.;Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA..
    O'Connor, Daniel T.
    Univ Calif San Diego, Dept Med, San Diego, CA 92093 USA..
    Ormel, Johan
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Dept Psychiat, POB 30001, NL-9700 RB Groningen, Netherlands..
    Perz, Siegfried
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany..
    Peters, Annette
    Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Partner Site, D-80336 Munich, Germany.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;German Ctr Diabet Res, D-85764 Neuherberg, Germany..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98104 USA.;Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland..
    Risbrough, Victoria B.
    Univ Calif San Diego, Dept Psychiat, San Diego, CA 92093 USA.;VA San Diego Healthcare Syst, Ctr Stress & Mental Hlth CESAMH, San Diego, CA 92161 USA..
    Sinner, Moritz F.
    Ludwig Maximilians Univ Munchen, Dept Med, Univ Hosp Munich, D-80539 Munich, Germany.;Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Partner Site, D-80336 Munich, Germany..
    Siscovick, David
    New York Acad Med, New York, NY 10029 USA..
    Smit, Johannes H.
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci, Dept Psychiat,GGZ inGeest, Campus Amsterdam, NL-1081 BT Amsterdam, Netherlands..
    Smith, Nicholas L.
    Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.;Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.;Vet Affairs Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA..
    Soliman, Elsayed Z.
    Wake Forest Sch Med, Div Publ Hlth Sci, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC 27157 USA..
    Sotoodehnia, Nona
    Univ Washington, Dept Med & Epidemiol, Div Cardiol, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA..
    Staessen, Jan A.
    Univ Leuven, KU Leuven Dept Cardiovasc Sci, Studies Coordinating Ctr, Res Unit Hypertens & Cardiovasc Epidemiol, B-3000 Leuven, Belgium..
    Stein, Phyllis K.
    Washington Univ, Heart Rate Variabil Lab, Sch Med, St Louis, MO 63108 USA..
    Stilp, Adrienne M.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Stolarz-Skrzypek, Katarzyna
    Jagiellonian Univ, Med Coll, Dept Cardiol Intervent Electrocardi & Hypertens 1, PL-31008 Krakow, Poland..
    Strauch, Konstantin
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany..
    Sundstrom, Johan
    Uppsala Univ, Dept Med Sci Cardiovasc Epidemiol, S-75185 Uppsala, Sweden..
    Swenne, Cees A.
    Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands..
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Tardif, Jean-Claude
    Montreal Heart Inst, Montreal, PQ H1T IC8, Canada.;Univ Montreal, Montreal, PQ H3T IJ4, Canada..
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat & Med, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Thornton, Timothy A.
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Tinker, Lesley E.
    Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA..
    Uitterlinden, Andre G.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, POB 2060, NL-3000 CB Rotterdam, Netherlands.;Erasmus Univ, Med Ctr, Dept Internal Med, NL-3015 CE Rotterdam, Netherlands.;Netherlands Consortium Hlth Aging, Netherlands Genom Initiat, NL-2300 RC Leiden, Netherlands..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Voss, Andreas
    IGHT Jena Ernst Abbe Hsch, Inst Innovat Hlth Technol, D-07745 Jena, Germany..
    Waldenberger, Melanie
    Dept Child & Adolescent Psychiat, Dept Child & Adolescent Psychiat Psychol, POB 2060, NL-3000 CB Rotterdam, Netherlands.;Helmholtz Zentrum Munchen, Inst Epidemiol 2, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany..
    Wilhelmsen, Kirk C.
    Univ N Carolina, Dept Genet & Neurol, Chapel Hill, NC 27599 USA.;Renaissance Comp Inst, Chapel Hill, NC 27599 USA..
    Willemsen, Gonneke
    Vrije Univ Amsterdam, Dept Biol Psychol Behav & Movement Sci, NL-1081 BT Amsterdam, Netherlands.;Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands..
    Wong, Quenna
    Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA..
    Zhang, Zhu-Ming
    Wake Forest Sch Med, Div Publ Hlth Sci, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27157 USA..
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Cusi, Daniele
    Italian Natl Res Council, CNR, Inst Biomed Technol, I-20090 Milan, Italy.;KOS Genet SRL, I-20091 Milan, Italy..
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Greiser, Halina K.
    German Canc Res Ctr, Div Canc Epidemiol, D-69210 Heidelberg, Germany..
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, POB 30001, NL-9700 RB Groningen, Netherlands..
    Hassan, Mohammad
    Sultan Qaboos Univ, Coll Med & Hlth Sci, Dept Physiol, Muscat Al Khou