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Nat Genet. 2017 Oct;49(10):1458-1467. doi: 10.1038/ng.3951. Epub 2017 Sep 11.

Genome-wide association study identifies 112 new loci for body mass index in the Japanese population.

Author information

1
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
2
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
3
Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
4
Laboratory for Omics Informatics, Omics Research Center, National Cerebral and Cardiovascular Center, Osaka, Japan.
5
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
6
Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
7
Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
8
Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
9
Graduate school of Frontier Sciences, the University of Tokyo, Tokyo, Japan.
10
Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
11
Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
12
Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medical University, Iwate, Japan.
13
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
14
Graduate School of Medicine, Tohoku University, Sendai, Japan.
15
Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
16
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
17
Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Abstract

Obesity is a risk factor for a wide variety of health problems. In a genome-wide association study (GWAS) of body mass index (BMI) in Japanese people (n = 173,430), we found 85 loci significantly associated with obesity (P < 5.0 × 10-8), of which 51 were previously unknown. We conducted trans-ancestral meta-analyses by integrating these results with the results from a GWAS of Europeans and identified 61 additional new loci. In total, this study identifies 112 novel loci, doubling the number of previously known BMI-associated loci. By annotating associated variants with cell-type-specific regulatory marks, we found enrichment of variants in CD19+ cells. We also found significant genetic correlations between BMI and lymphocyte count (P = 6.46 × 10-5, rg = 0.18) and between BMI and multiple complex diseases. These findings provide genetic evidence that lymphocytes are relevant to body weight regulation and offer insights into the pathogenesis of obesity.

PMID:
28892062
DOI:
10.1038/ng.3951
[Indexed for MEDLINE]

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