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Liu, C., Marioni, R. E., Hedman, Å. K., Pfeiffer, L., Tsai, P.-C., Reynolds, L. M., . . . Levy, D. (2018). A DNA methylation biomarker of alcohol consumption.. Molecular Psychiatry, 23, 422-433
Open this publication in new window or tab >>A DNA methylation biomarker of alcohol consumption.
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2018 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, p. 422-433Article in journal (Refereed) Published
Abstract [en]

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

National Category
Other Basic Medicine
Identifiers
urn:nbn:se:uu:diva-319698 (URN)10.1038/mp.2016.192 (DOI)000423441700028 ()27843151 (PubMedID)
Note

De tio första författarna delar på förstaförfattarskapet. De sex sista författarna delar på sistaförfattarskapet.

Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2018-03-19Bibliographically approved
Stubleski, J., Kukucka, P., Salihovic, S., Lind, P. M., Lind, L. & Kärrman, A. (2018). A method for analysis of marker persistent organic pollutants in low-volume plasma and serum samples using 96-well plate solid phase extraction.. Journal of Chromatography A, 1546, 18-27, Article ID S0021-9673(18)30253-X.
Open this publication in new window or tab >>A method for analysis of marker persistent organic pollutants in low-volume plasma and serum samples using 96-well plate solid phase extraction.
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2018 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1546, p. 18-27, article id S0021-9673(18)30253-XArticle in journal (Refereed) Published
Abstract [en]

The objective of this study was to develop and validate a 96-well plate solid phase extraction method for analysis of 23 lipophilic persistent organic pollutants (POPs) in low-volume plasma and serum samples which is applicable for biomonitoring and epidemiological studies. The analysis of selected markers for internal exposure: 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and polybrominated diphenylether 47 (BDE 47) was evaluated by comparing two SPE sorbents and GC-HRMS or GC-MS/MS detection. The final method extracted 23 POPs from 150 μL of serum and plasma using a 96-well extraction plate containing 60 mg Oasis HLB sorbent per well prior to GC-HRMS magnetic sector analysis. The extraction method was applied to 40 plasma samples collected for an epidemiological study. The recovery of selected POPs ranged from 31% to 63% (n = 48), and detection limits ranged from 2.2 to 45 pg/mL for PCBs, 4.2 to 167 pg/mL for OCPs, 7.8 pg/mL for OCDD and 6.1 pg/mL for BDE 47. This method showed good precision with relative standard deviations of selected POP concentrations in quality control samples (n = 48) ranging from 11% to 25%. The trueness was determined with standard reference material serum (n = 48) and the deviation from certified values ranged from 1 to 27%. Of the 23 POPs analyzed, 18 were detected in 43% to 100% of plasma samples collected for the epidemiological study. The method showed good robustness with low inter-well plate variation (11-31%) determined by twelve 96-well plate extractions, and can extract 96 samples, including quality controls and procedural blanks in 2-3 days. Comparison with GC-MS/MS analysis showed that similar concentrations (within 0.5% to 30%) of most POPs could be obtained with GC-APCI-MS/MS. Larger deviations were observed for PCB 194 (60%) and trans-nonachlor (43%). The developed method produces accurate concentrations of low-level marker POPs in plasma and serum, providing a suitable high-throughput sample preparation procedure for biomonitoring and epidemiological studies involving large sample size and limited sample volume. GC-HRMS was chosen over GC-MS/MS, however the latter showed promising results, and could be used as an alternative to GC-HRMS analysis for most POPs.

Place, publisher, year, edition, pages
Elsevier, 2018
Keyword
APCI-MS/MS, GC-HRMS, High-throughput SPE, Persistent organic pollutants
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-348564 (URN)10.1016/j.chroma.2018.02.057 (DOI)29510870 (PubMedID)
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-05-03Bibliographically approved
Cai, G.-H., Janson, C., Theorell-Haglöw, J., Benedict, C., Elmståhl, S., Lind, L. & Lindberg, E. (2018). Both Weight at Age 20 and Weight Gain Have an Impact on Sleep Disturbances Later in Life: Results of the EpiHealth Study. Sleep, 41(1), Article ID zsx176.
Open this publication in new window or tab >>Both Weight at Age 20 and Weight Gain Have an Impact on Sleep Disturbances Later in Life: Results of the EpiHealth Study
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2018 (English)In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 41, no 1, article id zsx176Article in journal (Refereed) Published
Abstract [en]

Study Objectives: Obesity is often associated with impaired sleep, whereas the impact of body mass index (BMI) at younger age and previous weight gain on sleep problems remains unknown.

Methods: The present study utilized data from the Swedish EpiHealth cohort study. A total of 15 845 participants (45-75 years) filled out an internet-based questionnaire. BMI was calculated from both measured data at study time and self-reported data at age 20 from the questionnaire.

Results: Sleep-related symptoms were most common among obese individuals (BMI >30 kg/m(2)). An association between weight gain and sleep problems was found and those with a low BMI at age 20 were most vulnerable to weight gain when it came to risk of sleep problems. Among those who were underweight (BMI <18.5 kg/m(2)) at age 20, weight gain (kg/year) was associated with difficulties initiating sleep with an adjusted OR of 2.64 (95% CI: 1.51-4.62) after adjusting for age, sex, smoking, alcohol consumption, physical activity, education, and civil status. The corresponding adjusted OR's among those who had been normal weight (BMI 18.5-24.99) and overweight (BMI 25-29.99 kg/m(2)) at age 20 were 1.89 (1.47-2.45) and 1.02 (0.48-2.13), respectively. Also difficulties maintaining sleep and snoring were most strongly related to weight gain among those who were underweight at age 20 with decreasing odds with increasing BMI at that age.

Conclusions: Sleep problems are related to weight gain and obesity. The impact of weight is most pronounced among those who had a low BMI when young.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS INC, 2018
Keyword
epidemiology, insomnia, obesity, aging, weight gain, EpiHealth study, body mass index (BMI), Epworth Sleepiness Scale (ESS), sleep problems, snoring
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-342460 (URN)10.1093/sleep/zsx176 (DOI)000422879100012 ()
Funder
Swedish Research Council
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-02-26Bibliographically approved
Mobacke, I., Lind, L., Dunder, L., Salihovic, S. & Lind, P. M. (2018). Circulating levels of perfluoroalkyl substances and left ventricular geometry of the heart in the elderly.. Environment International, 115, 295-300, Article ID S0160-4120(17)32060-3.
Open this publication in new window or tab >>Circulating levels of perfluoroalkyl substances and left ventricular geometry of the heart in the elderly.
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2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 115, p. 295-300, article id S0160-4120(17)32060-3Article in journal (Refereed) Epub ahead of print
Abstract [en]

AIMS: Some persistent organic pollutants (POPs) such as hexachlorobenzene (HCB) and some polychlorinated biphenyls (PCBs) have been shown to interfere with myocardial function and geometry. We therefore investigated if also another group of POPs: per- and polyfluoroalkyl substances (PFASs) were associated with alterations in left ventricular geometry.

METHODS: 801 subjects aged 70 years were investigated in a cross-sectional study within the scope of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants´ plasma by ultra-performance liquid chromatograph/tandem mass spectrometry. Left ventricular geometry was determined by echocardiography. Multivariable linear regression was used to investigate the associations between PFASs and left ventricular geometry of the heart after exclusion of subjects with previous myocardial infarction (n = 72).

RESULTS: When adjusting for multiple comparisons, none of the eight PFASs evaluated were significantly related to left ventricular mass. However, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were related to relative wall thickness (RWT) in a negative fashion (p < 0.0021). Besides being inversely related to RWT, PFNA was also positively related to left ventricular end-diastolic volume (LVEDD) (p < 0.0021). These analyses were adjusted for traditional cardiovascular risk factors.

CONCLUSION: In this cross-sectional study, several of the PFASs evaluated, especially PFNA, were related to myocardial geometry: a reduction in relative wall thickness and an increase in left ventricular diameter following adjustment for traditional cardiovascular risk factors, suggesting a role for PFASs in cardiac remodeling.

Keyword
Elderly, Environmental contaminants, Heart, Left ventricular geometry, Per- and polyfluoroalkyl substances (PFASs), Perfluorononanoic acid (PFNA)
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-348565 (URN)10.1016/j.envint.2018.03.033 (DOI)29621717 (PubMedID)
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-05-09Bibliographically approved
Stenemo, M., Nowak, C., Byberg, L., Sundström, J., Giedraitis, V., Lind, L., . . . Ärnlöv, J. (2018). Circulating proteins as predictors of incident heart failure in the elderly. European Journal of Heart Failure, 20(1), 55-62
Open this publication in new window or tab >>Circulating proteins as predictors of incident heart failure in the elderly
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2018 (English)In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 20, no 1, p. 55-62Article in journal (Refereed) Published
Abstract [en]

Aims

To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology.

Methods and results

Proteomic profiling (proximity extension assay) was performed in two community‐based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0–70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9–78.1) years, 90 events]. Twenty‐nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF‐15), T‐cell immunoglobulin and mucin domain 1 (TIM‐1), tumour necrosis factor‐related apoptosis‐inducing ligand receptor 2 (TRAIL‐R2), spondin‐1 (SPON1), matrix metalloproteinase‐12 (MMP‐12), follistatin (FS), urokinase‐type plasminogen activator surface receptor (U‐PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF‐15, U‐PAR, MMP‐12, TRAIL‐R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM‐1 was positively associated with worsened diastolic function (P < 0.02 for all).

Conclusion

Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.

Keyword
Biomarkers, Epidemiology, Heart failure, Left ventricular dysfunction, Proteomics, Risk prediction
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-334416 (URN)10.1002/ejhf.980 (DOI)000423809700007 ()28967680 (PubMedID)
Funder
EU, Horizon 2020, 634869Swedish Research Council, 2012-2215; 2015-03477; 221-2013-1673Marianne and Marcus Wallenberg Foundation, 2012.0082Swedish Heart Lung Foundation, 20140422; 20150429; 20120169Knut and Alice Wallenberg Foundation, 2013.0126Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of Technology, 1637
Note

Tove Fall och Johan Ärnlöv delar på sistaförfattarskapet.

Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2018-03-23Bibliographically approved
Genberg, M., Andrén, B., Lind, L., Hedenström, H. & Malinovschi, A. (2018). Commonly used reference values underestimate oxygen uptake in healthy, 50-year-old Swedish women.. Clinical Physiology and Functional Imaging, 38(1), 25-33
Open this publication in new window or tab >>Commonly used reference values underestimate oxygen uptake in healthy, 50-year-old Swedish women.
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2018 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 1, p. 25-33Article in journal (Refereed) Published
Abstract [en]

Cardiopulmonary exercise testing (CPET) is the gold standard among clinical exercise tests. It combines a conventional stress test with measurement of oxygen uptake (VO2 ) and CO2 production. No validated Swedish reference values exist, and reference values in women are generally understudied. Moreover, the importance of achieved respiratory exchange ratio (RER) and the significance of breathing reserve (BR) at peak exercise in healthy individuals are poorly understood. We compared VO2 at maximal load (peakVO2 ) and anaerobic threshold (VO2@AT ) in healthy Swedish individuals with commonly used reference values, taking gender into account. Further, we analysed maximal workload and peakVO2 with regard to peak RER and BR. In all, 181 healthy, 50-year-old individuals (91 women) performed CPET. PeakVO2 was best predicted using Jones et al. (100·5%), while SHIP reference values underestimated peakVO2 most: 112·5%. Furthermore, underestimation of peakVO2 in women was found for all studied reference values (P<0·001) and was largest for SHIP: women had 128% of predicted peakVO2 , while men had 104%. PeakVO2 was similar in subjects with peak RER of 1-1·1 and RER > 1·1 (2 328·7 versus 2 176·7 ml min(-1) , P = 0·11). Lower BR (≤30%) related to significantly higher peakVO2 (P<0·001). In conclusion, peakVO2 was best predicted by Jones. All studied reference values underestimated oxygen uptake in women. No evidence for demanding RER > 1·1 in healthy individuals was found. A lowered BR is probably a normal response to higher workloads in healthy individuals.

National Category
Cardiac and Cardiovascular Systems Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-312359 (URN)10.1111/cpf.12377 (DOI)000417877700005 ()27312352 (PubMedID)
Available from: 2017-01-09 Created: 2017-01-09 Last updated: 2018-01-17Bibliographically approved
Jiang, X., O'Reilly, P. F., Aschard, H., Hsu, Y.-H., Richards, J. B., Dupuis, J., . . . Kiel, D. P. (2018). Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. Nature Communications, 9, Article ID 260.
Open this publication in new window or tab >>Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
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2018 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 260Article in journal (Refereed) Published
Abstract [en]

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10−9 at rs8018720 in SEC23A, and P = 1.9×10−14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-343676 (URN)10.1038/s41467-017-02662-2 (DOI)000422650500011 ()29343764 (PubMedID)
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2018-03-05Bibliographically approved
Lind, P. M., Salihovic, S. & Lind, L. (2018). High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis.. Environment International, 113, 109-113, Article ID S0160-4120(17)31841-X.
Open this publication in new window or tab >>High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis.
2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 113, p. 109-113, article id S0160-4120(17)31841-XArticle in journal (Refereed) Published
Abstract [en]

BACKGROUND: Organochlorine pesticides (OCPs) have been shown in the experimental setting to alter DNA methylation. Since DNA methylation changes during the life-span, formulas have been presented to calculate "DNA methylation age" as a measure of biological age.

OBJECTIVES: We aimed to investigate if circulating levels of three OCPs were related to increased DNA methylation age METHODS: 71CpG DNA methylation age (Hannum formula) was calculated based on data from the Illumina 450 k Bead Methylation chip in 1000 subjects in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between DNA methylation age and chronological age was calculated (DiffAge). 2,2-bis (4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), hexachlorobenzene (HCB), and transnonachlor (TNC) levels were measured in plasma by high-resolution gas chromatography coupled mass spectrometry (HRGC-HRMS).

RESULTS: Increased p,p'-DDE and TNC, but not HCB, levels were related to increased DiffAge both in sex and BMI-adjusted models, as well as in multiple adjusted models (sex, education level, exercise habits, smoking, energy and alcohol consumption and BMI) (p = 0.0051 and p = 0.011, respectively). No significant interactions between the OCPs and sex or BMI regarding DiffAge were found.

CONCLUSION: In this cross-sectional study, increased levels of two out of three OCPs were related to increased DNA methylation age, further suggesting negative health effects in humans of these widespread environmental contaminants.

Place, publisher, year, edition, pages
Elsevier, 2018
Keyword
Biological age, Epidemiology, Methylation, Organochlorine pesticides (OCPs), Transnonachlor, p, p′-DDE
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:uu:diva-348563 (URN)10.1016/j.envint.2018.01.019 (DOI)29421399 (PubMedID)
Available from: 2018-04-16 Created: 2018-04-16 Last updated: 2018-05-09Bibliographically approved
Velickaite, V., Ferreira, D., Cavallin, L., Lind, L., Ahlström, H., Kilander, L., . . . Larsson, E.-M. (2018). Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort: gender-corrected and education-corrected normative data. European Radiology, 28(4), 1739-1747
Open this publication in new window or tab >>Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort: gender-corrected and education-corrected normative data
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2018 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 28, no 4, p. 1739-1747Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To find cut-off values for different medial temporal lobe atrophy (MTA) measures (right, left, average, and highest), accounting for gender and education, investigate the association with cognitive performance, and to compare with decline of cognitive function over 5 years in a large population-based cohort.

METHODS: Three hundred and ninety 75-year-old individuals were examined with magnetic resonance imaging of the brain and cognitive testing. The Scheltens's scale was used to assess visually MTA scores (0-4) in all subjects. Cognitive tests were repeated in 278 of them after 5 years. Normal MTA cut-off values were calculated based on the 10th percentile.

RESULTS: Most 75-year-old individuals had MTA score ≤2. Men had significantly higher MTA scores than women. Scores for left and average MTA were significantly higher in highly educated individuals. Abnormal MTA was associated with worse results in cognitive test and individuals with abnormal right MTA had faster cognitive decline.

CONCLUSION: At age 75, gender and education are confounders for MTA grading. A score of ≥2 is abnormal for low-educated women and a score of ≥2.5 is abnormal for men and high-educated women. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later.

KEY POINTS: • Gender and education are confounders for MTA grading. • We suggest cut-off values for 75-year-olds, taking gender and education into account. • Males have higher MTA scores than women. • Higher MTA scores are associated with worse cognitive performance.

Keyword
Cognitive test, Dementia, Longitudinal analysis, Medial temporal lobe atrophy (MTA), Population-based, Scheltens’s scale
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-333774 (URN)10.1007/s00330-017-5103-6 (DOI)000426645600044 ()29124383 (PubMedID)
Funder
Stockholm County CouncilThe Karolinska Institutet's Research Foundation
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-05-15Bibliographically approved
Lind, L., Ingelsson, E., Sundström, J., Siegbahn, A. & Lampa, E. (2018). Methylation-based estimated biological age and cardiovascular disease.. European Journal of Clinical Investigation, 48(2), Article ID e12872.
Open this publication in new window or tab >>Methylation-based estimated biological age and cardiovascular disease.
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2018 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 48, no 2, article id e12872Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: DNA methylation changes over life at specific sites in the genome, which can be used to estimate "biological age." The aim of this population-based longitudinal cohort study was to investigate the association between estimated biological age and incident cardiovascular disease (CVD).

MATERIALS AND METHODS: Based on formulas published by Hannum et al and Horvath et al, "biological age" was calculated using data from the Illumina 450k Bead Methylation chip in 832 participants free from cardiovascular disease in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between estimated biological and chronological age was calculated (DiffAge).

RESULTS: During 10 years of follow-up, 153 incident cases of cardiovascular disease occurred. In the sex-adjusted analyses, the Horvath estimation of DiffAge was significantly related to incident cardiovascular disease (HR 1.040, 95% CI 1.010-1.071, P = .0079). Thus, for each year of increased biological age, a 4% increased risk of future cardiovascular disease was observed. This relationship was still significant following adjustment for the traditional risk factors sex, BMI, diabetes, HDL and LDL-cholesterol, systolic blood pressure and smoking (HR 1.033, 95% CI 1.004-1.063, P = .024). No such significant association was found using the Hannum formula.

CONCLUSIONS: DNA methylation-based estimation of "biological age" per Horvath was associated with incident cardiovascular disease.

Keyword
DNA, age, cardiovascular diseases, methylation, risk factors
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-343485 (URN)10.1111/eci.12872 (DOI)000423370500006 ()29231988 (PubMedID)
Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-03-07Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2335-8542

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