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PMID: 28892062 Published · ppublish English Comparative Study Journal Article Meta-Analysis

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

Nature genetics ·Vol. 49 ·No. 10 ·2017-10-00 ·Pages 1458-1467

Akiyama M, Okada Y, Kanai M, Takahashi A, Momozawa Y, Ikeda M, Iwata N, Ikegawa S, Hirata M, Matsuda K, Iwasaki M, Yamaji T, Sawada N, Hachiya T, Tanno K, Shimizu A, Hozawa A, Minegishi N, Tsugane S, Yamamoto M, Kubo M, Kamatani Y

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.

MeSH Terms
Asians/genetics Body Mass Index Body Weight/genetics,physiology Comorbidity Diabetes Mellitus, Type 2/ethnology,genetics Europe/epidemiology Genome-Wide Association Study Humans Japan/epidemiology Lymphocyte Count Obesity/ethnology,genetics,immunology Polymorphism, Single Nucleotide Whites/genetics
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Akiyama Masato
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Okada Yukinori
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. | Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan. | Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan.
Kanai Masahiro ORCID
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Takahashi Atsushi ORCID
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. | Laboratory for Omics Informatics, Omics Research Center, National Cerebral and Cardiovascular Center, Osaka, Japan.
Momozawa Yukihide
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Ikeda Masashi
Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
Iwata Nakao ORCID
Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
Ikegawa Shiro
Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
Hirata Makoto
Institute of Medical Science, the University of Tokyo, Tokyo, Japan.
Matsuda Koichi ORCID
Graduate school of Frontier Sciences, the University of Tokyo, Tokyo, Japan.
Iwasaki Motoki
Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
Yamaji Taiki
Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
Sawada Norie
Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
Hachiya Tsuyoshi
Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
Tanno Kozo
Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan. | Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medical University, Iwate, Japan.
Shimizu Atsushi
Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
Hozawa Atsushi
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan. | Graduate School of Medicine, Tohoku University, Sendai, Japan.
Minegishi Naoko
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan. | Graduate School of Medicine, Tohoku University, Sendai, Japan.
Tsugane Shoichiro ORCID
Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
Yamamoto Masayuki
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan. | Graduate School of Medicine, Tohoku University, Sendai, Japan.
Kubo Michiaki
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Kamatani Yoichiro ORCID
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. | Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.3951
Published
2017-10-00
Epub
2017-00-11
Pages
1458-1467
Language
English
Region
United States
NLM ID
9216904
Subset
IM
External Links
PubMed source DOI: 10.1038/ng.3951 View journal details
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