Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.
BMI
DNA methylation
adiposity
epigenome-wide association study
epigenomics
metabolic disease
obesity
prediction
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
02 02 2023
02 02 2023
Historique:
received:
27
07
2022
accepted:
20
12
2022
pubmed:
18
1
2023
medline:
8
2
2023
entrez:
17
1
2023
Statut:
ppublish
Résumé
This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Women's Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the pooled EWASs, 1,265 CpG sites were associated with BMI (p < 1E-7) and 1,238 replicated in the WHI (FDR < 0.05). We performed several stratified analyses to examine whether these associations differed between individuals of European and African descent, as defined by self-reported race/ethnicity. We found that five CpG sites had a significant interaction with BMI by race/ethnicity. To examine the utility of the significant CpG sites in predicting BMI, we used elastic net regression to predict log-normalized BMI in the WHI (80% training/20% testing). This model found that 397 sites could explain 32% of the variance in BMI in the WHI test set. Individuals whose methylome-predicted BMI overestimated their BMI (high epigenetic BMI) had significantly higher glucose and triglycerides and lower HDL cholesterol and LDL cholesterol compared to accurately predicted BMI. Individuals whose methylome-predicted BMI underestimated their BMI (low epigenetic BMI) had significantly higher HDL cholesterol and lower glucose and triglycerides. This study confirmed 553 and identified 685 CpG sites associated with BMI. Participants with high epigenetic BMI had poorer metabolic health, suggesting that the overestimation may be driven in part by cardiometabolic derangements characteristic of metabolic syndrome.
Identifiants
pubmed: 36649705
pii: S0002-9297(22)00548-1
doi: 10.1016/j.ajhg.2022.12.014
pmc: PMC9943731
pii:
doi:
Substances chimiques
Cholesterol, HDL
0
Triglycerides
0
Types de publication
Meta-Analysis
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
273-283Subventions
Organisme : NIEHS NIH HHS
ID : R01 ES020836
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 HG200362
Pays : United States
Organisme : NHLBI NIH HHS
ID : RC2 HL102419
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS087541
Pays : United States
Informations de copyright
Copyright © 2022 American Society of Human Genetics. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests K.M.J. is an employee of Bristol Myers Squibb.
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