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Am J Epidemiol. 2018 Aug 1;187(8):1662-1669. doi: 10.1093/aje/kwy025.

An Epigenome-Wide Association Study of Obesity-Related Traits.

Author information

1
Department of Epidemiology, Erasmus University Medical Center.
2
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
3
Rotterdam Intergenerational Ageing Research Center.
4
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
5
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota.
6
Human Genetics Center, School of Public Health, University of Texas Health Sciences Center at Houston, Houston, Texas.
7
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
8
Department of Internal Medicine, Erasmus University Medical Center.
9
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
10
Department of Epidemiology, Imperial College London, London, United Kingdom.

Abstract

We conducted an epigenome-wide association study on obesity-related traits. We used data from 2 prospective, population-based cohort studies: the Rotterdam Study (RS) (2006-2013) and the Atherosclerosis Risk in Communities (ARIC) Study (1990-1992). We used the RS (n = 1,450) as the discovery panel and the ARIC Study (n = 2,097) as the replication panel. Linear mixed-effect models were used to assess the cross-sectional associations between genome-wide DNA methylation in leukocytes and body mass index (BMI) and waist circumference (WC), adjusting for sex, age, smoking, leukocyte proportions, array number, and position on array. The latter 2 variables were modeled as random effects. Fourteen 5'-C-phosphate-G-3' (CpG) sites were associated with BMI and 26 CpG sites with WC in the RS after Bonferroni correction (P < 1.07 × 10-7), of which 12 and 13 CpGs were replicated in the ARIC Study, respectively. The most significant novel CpGs were located on the Musashi RNA binding protein 2 gene (MSI2; cg21139312) and the leucyl-tRNA synthetase 2, mitochondrial gene (LARS2; cg18030453) and were associated with both BMI and WC. CpGs at BRDT, PSMD1, IFI44L, MAP1A, and MAP3K5 were associated with BMI. CpGs at LGALS3BP, MAP2K3, DHCR24, CPSF4L, and TMEM49 were associated with WC. We report novel associations between methylation at MSI2 and LARS2 and obesity-related traits. These results provide further insight into mechanisms underlying obesity-related traits, which can enable identification of new biomarkers in obesity-related chronic diseases.

PMID:
29762635
PMCID:
PMC6070087
DOI:
10.1093/aje/kwy025

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