An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort

Olivia K L Hamilton, Qian Zhang, Allan F McRae, Rosie M Walker, Stewart W Morris, Paul Redmond, Archie Campbell, Alison D Murray, David J Porteous, Kathryn L Evans, Andrew M McIntosh, Ian J Deary, Riccardo E Marioni (Corresponding Author)

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Abstract

BACKGROUND: The relationship between obesity and adverse health is well established, but little is known about the contribution of DNA methylation to obesity-related health outcomes. This study tests associations between an epigenetic score for body mass index (BMI) and health-related, cognitive, psychosocial and lifestyle outcomes in the Lothian Birth Cohort 1936. This study also tests whether these associations are independent of phenotypic BMI.

METHOD: Analyses were conducted using data from the Lothian Birth Cohort 1936 (n = 892). Weights for the epigenetic BMI score were derived using penalised regression on methylation data from unrelated Generation Scotland participants (n = 2562). Associations were tested for replication in an independent sample: the Lothian Birth Cohort 1921 (n = 433).

RESULTS: A higher epigenetic BMI score was associated with higher BMI (R2 = 0.1), greater body weight (R2 = 0.06), greater time taken to walk 6 m, poorer lung function and poorer general physical health (all R2 = 0.02), greater levels of triglycerides (R2 = 0.09), greater %total HbA1c (R2 = 0.06), lower levels of high-density lipoprotein cholesterol (HDL; R2 = 0.08), higher HDL ratio (HDL/total cholesterol; R2 = 0.03), lower health-related quality of life, physical inactivity, and greater social deprivation (all R2 = 0.02). The epigenetic BMI score (per SD) was also associated with type 2 diabetes (OR 2.17, 95% CI 1.67, 2.84), cardiovascular disease (OR 1.45, 95% CI 1.24, 1.71) and high blood pressure (OR 1.30, 95% CI 1.13, 1.49; all p < 0.00026 after Bonferroni correction). Associations were replicated for BMI (R2 = 0.06), body weight (R2 = 0.04), health-related quality of life (R2 = 0.02), HbA1c (R2 = 0.07) and triglycerides (R2 = 0.07; all p < 0.0045 after Bonferroni correction).

CONCLUSIONS: We observed and replicated associations between an epigenetic score for BMI and variables related to poor physical health and metabolic syndrome. Regression models with both epigenetic and phenotypic BMI scores as predictors accounted for a greater proportion of variance in all outcome variables than either predictor alone, demonstrating independent and additive effects of epigenetic and phenotypic BMI scores.

Original languageEnglish
Pages (from-to)1795-1802
Number of pages8
JournalInternational Journal of Obesity
Volume43
DOIs
Publication statusPublished - 6 Mar 2019

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DNA Methylation
Epigenomics
Body Mass Index
Parturition
Health
HDL Cholesterol
Triglycerides
Obesity
Body Weight
Quality of Life
Scotland
Type 2 Diabetes Mellitus
Methylation
Life Style
Cardiovascular Diseases
Hypertension
Weights and Measures
Lung

Keywords

  • FOOD-FREQUENCY QUESTIONNAIRE
  • EPIGENOME-WIDE ASSOCIATION
  • BODY-MASS INDEX
  • WEIGHT-LOSS
  • LIFE
  • VALIDITY
  • PATTERNS
  • OBESE
  • HIF3A

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism

Cite this

An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort. / Hamilton, Olivia K L; Zhang, Qian; McRae, Allan F; Walker, Rosie M; Morris, Stewart W; Redmond, Paul; Campbell, Archie; Murray, Alison D; Porteous, David J; Evans, Kathryn L; McIntosh, Andrew M; Deary, Ian J; Marioni, Riccardo E (Corresponding Author).

In: International Journal of Obesity, Vol. 43, 06.03.2019, p. 1795-1802.

Research output: Contribution to journalArticle

Hamilton, OKL, Zhang, Q, McRae, AF, Walker, RM, Morris, SW, Redmond, P, Campbell, A, Murray, AD, Porteous, DJ, Evans, KL, McIntosh, AM, Deary, IJ & Marioni, RE 2019, 'An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort', International Journal of Obesity, vol. 43, pp. 1795-1802. https://doi.org/10.1038/s41366-018-0262-3
Hamilton, Olivia K L ; Zhang, Qian ; McRae, Allan F ; Walker, Rosie M ; Morris, Stewart W ; Redmond, Paul ; Campbell, Archie ; Murray, Alison D ; Porteous, David J ; Evans, Kathryn L ; McIntosh, Andrew M ; Deary, Ian J ; Marioni, Riccardo E. / An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort. In: International Journal of Obesity. 2019 ; Vol. 43. pp. 1795-1802.
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title = "An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort",
abstract = "BACKGROUND: The relationship between obesity and adverse health is well established, but little is known about the contribution of DNA methylation to obesity-related health outcomes. This study tests associations between an epigenetic score for body mass index (BMI) and health-related, cognitive, psychosocial and lifestyle outcomes in the Lothian Birth Cohort 1936. This study also tests whether these associations are independent of phenotypic BMI.METHOD: Analyses were conducted using data from the Lothian Birth Cohort 1936 (n = 892). Weights for the epigenetic BMI score were derived using penalised regression on methylation data from unrelated Generation Scotland participants (n = 2562). Associations were tested for replication in an independent sample: the Lothian Birth Cohort 1921 (n = 433).RESULTS: A higher epigenetic BMI score was associated with higher BMI (R2 = 0.1), greater body weight (R2 = 0.06), greater time taken to walk 6 m, poorer lung function and poorer general physical health (all R2 = 0.02), greater levels of triglycerides (R2 = 0.09), greater {\%}total HbA1c (R2 = 0.06), lower levels of high-density lipoprotein cholesterol (HDL; R2 = 0.08), higher HDL ratio (HDL/total cholesterol; R2 = 0.03), lower health-related quality of life, physical inactivity, and greater social deprivation (all R2 = 0.02). The epigenetic BMI score (per SD) was also associated with type 2 diabetes (OR 2.17, 95{\%} CI 1.67, 2.84), cardiovascular disease (OR 1.45, 95{\%} CI 1.24, 1.71) and high blood pressure (OR 1.30, 95{\%} CI 1.13, 1.49; all p < 0.00026 after Bonferroni correction). Associations were replicated for BMI (R2 = 0.06), body weight (R2 = 0.04), health-related quality of life (R2 = 0.02), HbA1c (R2 = 0.07) and triglycerides (R2 = 0.07; all p < 0.0045 after Bonferroni correction).CONCLUSIONS: We observed and replicated associations between an epigenetic score for BMI and variables related to poor physical health and metabolic syndrome. Regression models with both epigenetic and phenotypic BMI scores as predictors accounted for a greater proportion of variance in all outcome variables than either predictor alone, demonstrating independent and additive effects of epigenetic and phenotypic BMI scores.",
keywords = "FOOD-FREQUENCY QUESTIONNAIRE, EPIGENOME-WIDE ASSOCIATION, BODY-MASS INDEX, WEIGHT-LOSS, LIFE, VALIDITY, PATTERNS, OBESE, HIF3A",
author = "Hamilton, {Olivia K L} and Qian Zhang and McRae, {Allan F} and Walker, {Rosie M} and Morris, {Stewart W} and Paul Redmond and Archie Campbell and Murray, {Alison D} and Porteous, {David J} and Evans, {Kathryn L} and McIntosh, {Andrew M} and Deary, {Ian J} and Marioni, {Riccardo E}",
note = "Acknowledgements: The authors thank all LBC study participants and research team members who have contributed, and continue to contribute, to the ongoing LBC study. The LBC1936 is supported by Age UK (Disconnected Mind programme) and the Medical Research Council [MR/M01311/1]. The LBC1921 is supported by the Biotechnology and Biological Sciences Research Council [SR176], the Chief Scientist Office [CZB/4/505; ETM/55] and the Medical Research Council [R42550]. Methylation typing was supported by the Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. This work was conducted in the Centre for Cognitive Ageing and Cognitive Epidemiology, which is supported by the Medical Research Council and Biotechnology and Biological Sciences Research Council [MR/K026992/1], and which supports Ian Deary. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” [(STRADL) 104036/Z/14/Z])",
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TY - JOUR

T1 - An epigenetic score for BMI based on DNA methylation correlates with poor physical health and major disease in the Lothian Birth Cohort

AU - Hamilton, Olivia K L

AU - Zhang, Qian

AU - McRae, Allan F

AU - Walker, Rosie M

AU - Morris, Stewart W

AU - Redmond, Paul

AU - Campbell, Archie

AU - Murray, Alison D

AU - Porteous, David J

AU - Evans, Kathryn L

AU - McIntosh, Andrew M

AU - Deary, Ian J

AU - Marioni, Riccardo E

N1 - Acknowledgements: The authors thank all LBC study participants and research team members who have contributed, and continue to contribute, to the ongoing LBC study. The LBC1936 is supported by Age UK (Disconnected Mind programme) and the Medical Research Council [MR/M01311/1]. The LBC1921 is supported by the Biotechnology and Biological Sciences Research Council [SR176], the Chief Scientist Office [CZB/4/505; ETM/55] and the Medical Research Council [R42550]. Methylation typing was supported by the Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. This work was conducted in the Centre for Cognitive Ageing and Cognitive Epidemiology, which is supported by the Medical Research Council and Biotechnology and Biological Sciences Research Council [MR/K026992/1], and which supports Ian Deary. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” [(STRADL) 104036/Z/14/Z])

PY - 2019/3/6

Y1 - 2019/3/6

N2 - BACKGROUND: The relationship between obesity and adverse health is well established, but little is known about the contribution of DNA methylation to obesity-related health outcomes. This study tests associations between an epigenetic score for body mass index (BMI) and health-related, cognitive, psychosocial and lifestyle outcomes in the Lothian Birth Cohort 1936. This study also tests whether these associations are independent of phenotypic BMI.METHOD: Analyses were conducted using data from the Lothian Birth Cohort 1936 (n = 892). Weights for the epigenetic BMI score were derived using penalised regression on methylation data from unrelated Generation Scotland participants (n = 2562). Associations were tested for replication in an independent sample: the Lothian Birth Cohort 1921 (n = 433).RESULTS: A higher epigenetic BMI score was associated with higher BMI (R2 = 0.1), greater body weight (R2 = 0.06), greater time taken to walk 6 m, poorer lung function and poorer general physical health (all R2 = 0.02), greater levels of triglycerides (R2 = 0.09), greater %total HbA1c (R2 = 0.06), lower levels of high-density lipoprotein cholesterol (HDL; R2 = 0.08), higher HDL ratio (HDL/total cholesterol; R2 = 0.03), lower health-related quality of life, physical inactivity, and greater social deprivation (all R2 = 0.02). The epigenetic BMI score (per SD) was also associated with type 2 diabetes (OR 2.17, 95% CI 1.67, 2.84), cardiovascular disease (OR 1.45, 95% CI 1.24, 1.71) and high blood pressure (OR 1.30, 95% CI 1.13, 1.49; all p < 0.00026 after Bonferroni correction). Associations were replicated for BMI (R2 = 0.06), body weight (R2 = 0.04), health-related quality of life (R2 = 0.02), HbA1c (R2 = 0.07) and triglycerides (R2 = 0.07; all p < 0.0045 after Bonferroni correction).CONCLUSIONS: We observed and replicated associations between an epigenetic score for BMI and variables related to poor physical health and metabolic syndrome. Regression models with both epigenetic and phenotypic BMI scores as predictors accounted for a greater proportion of variance in all outcome variables than either predictor alone, demonstrating independent and additive effects of epigenetic and phenotypic BMI scores.

AB - BACKGROUND: The relationship between obesity and adverse health is well established, but little is known about the contribution of DNA methylation to obesity-related health outcomes. This study tests associations between an epigenetic score for body mass index (BMI) and health-related, cognitive, psychosocial and lifestyle outcomes in the Lothian Birth Cohort 1936. This study also tests whether these associations are independent of phenotypic BMI.METHOD: Analyses were conducted using data from the Lothian Birth Cohort 1936 (n = 892). Weights for the epigenetic BMI score were derived using penalised regression on methylation data from unrelated Generation Scotland participants (n = 2562). Associations were tested for replication in an independent sample: the Lothian Birth Cohort 1921 (n = 433).RESULTS: A higher epigenetic BMI score was associated with higher BMI (R2 = 0.1), greater body weight (R2 = 0.06), greater time taken to walk 6 m, poorer lung function and poorer general physical health (all R2 = 0.02), greater levels of triglycerides (R2 = 0.09), greater %total HbA1c (R2 = 0.06), lower levels of high-density lipoprotein cholesterol (HDL; R2 = 0.08), higher HDL ratio (HDL/total cholesterol; R2 = 0.03), lower health-related quality of life, physical inactivity, and greater social deprivation (all R2 = 0.02). The epigenetic BMI score (per SD) was also associated with type 2 diabetes (OR 2.17, 95% CI 1.67, 2.84), cardiovascular disease (OR 1.45, 95% CI 1.24, 1.71) and high blood pressure (OR 1.30, 95% CI 1.13, 1.49; all p < 0.00026 after Bonferroni correction). Associations were replicated for BMI (R2 = 0.06), body weight (R2 = 0.04), health-related quality of life (R2 = 0.02), HbA1c (R2 = 0.07) and triglycerides (R2 = 0.07; all p < 0.0045 after Bonferroni correction).CONCLUSIONS: We observed and replicated associations between an epigenetic score for BMI and variables related to poor physical health and metabolic syndrome. Regression models with both epigenetic and phenotypic BMI scores as predictors accounted for a greater proportion of variance in all outcome variables than either predictor alone, demonstrating independent and additive effects of epigenetic and phenotypic BMI scores.

KW - FOOD-FREQUENCY QUESTIONNAIRE

KW - EPIGENOME-WIDE ASSOCIATION

KW - BODY-MASS INDEX

KW - WEIGHT-LOSS

KW - LIFE

KW - VALIDITY

KW - PATTERNS

KW - OBESE

KW - HIF3A

UR - http://www.scopus.com/inward/record.url?scp=85062630117&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/epigenetic-score-bmi-based-dna-methylation-correlates-poor-physical-health-major-disease-lothian-bir

U2 - 10.1038/s41366-018-0262-3

DO - 10.1038/s41366-018-0262-3

M3 - Article

VL - 43

SP - 1795

EP - 1802

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

ER -