Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.

Autor:	Do WL; Laney Graduate School, Emory University, Atlanta, GA, USA., Sun D; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA., Meeks K; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands., Dugué PA; Precision Medicine, School of Clinical Sciences At Monash Health, Monash University, Clayton, VIC, Australia; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC 3051, Australia., Demerath E; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA., Guan W; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA., Li S; Children's Minnesota Research Institute, Childrens Minnesota, Minneapolis, MN, USA., Chen W; Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA., Milne R; Precision Medicine, School of Clinical Sciences At Monash Health, Monash University, Clayton, VIC, Australia; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC 3051, Australia., Adeyemo A; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA., Agyemang C; Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands., Nassir R; Department of Pathology, School of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia., Manson JE; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Shadyab AH; Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA., Hou L; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA., Horvath S; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA., Assimes TL; Department of Medicine, School of Medicine, Stanford University, Stanford, CA, USA., Bhatti P; Cancer Control Research, BC Cancer, Vancouver, BC, Canada., Jordahl KM; Department of Epidemiology, University of Washington, Seattle, WA, USA., Baccarelli AA; Department of Environmental Health Sciences, Columbia University, New York, NY, USA., Smith AK; Department of Gynecology and Obstetrics, School of Medicine, Emory University, Atlanta, GA, USA., Staimez LR; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Stein AD; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Whitsel EA; Departments of Epidemiology and Medicine, University of North Carolina, Chapel Hill, NC, USA., Narayan KMV; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Conneely KN; Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA. Electronic address: kconnee@emory.edu.
Jazyk:	angličtina
Zdroj:	American journal of human genetics [Am J Hum Genet] 2023 Feb 02; Vol. 110 (2), pp. 273-283. Date of Electronic Publication: 2023 Jan 16.
DOI:	10.1016/j.ajhg.2022.12.014
Abstrakt:	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. Competing Interests: Declaration of interests K.M.J. is an employee of Bristol Myers Squibb. (Copyright © 2022 American Society of Human Genetics. All rights reserved.)
Databáze:	MEDLINE
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