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

被引：356

作者：

Akiyama, Masato ^{[1
]}

Okada, Yukinori ^{[1
,2
,3
]}

Kanai, Masahiro ^{[1
]}

Takahashi, Atsushi ^{[1
,4
]}

Momozawa, Yukihide ^{[5
]}

Ikeda, Masashi ^{[6
]}

Iwata, Nakao ^{[6
]}

Ikegawa, Shiro ^{[7
]}

Hirata, Makoto ^{[8
]}

Matsuda, Koichi ^{[9
]}

Iwasaki, Motoki ^{[10
]}

Yamaji, Taiki ^{[10
]}

Sawada, Norie ^{[10
]}

Hachiya, Tsuyoshi ^{[11
]}

Tanno, Kozo ^{[11
,12
]}

Shimizu, Atsushi ^{[11
]}

Hozawa, Atsushi ^{[13
,14
]}

Minegishi, Naoko ^{[13
,14
]}

Tsugane, Shoichiro ^{[15
]}

Yamamoto, Masayuki ^{[13
,14
]}

Kubo, Michiaki ^{[16
]}

Kamatani, Yoichiro ^{[1
,17
]}

机构：

[1] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan

[2] Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan

[3] Osaka Univ, Lab Stat Immunol, Immunol Frontier Res Ctr WPI IFReC, Suita, Osaka, Japan

[4] Natl Cerebral & Cardiovasc Ctr, Omics Res Ctr, Lab Omics Informat, Osaka, Japan

[5] RIKEN Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[6] Fujita Hlth Univ, Dept Psychiat, Sch Med, Toyoake, Aichi, Japan

[7] RIKEN Ctr Integrat Med Sci, Lab Bone & Joint Dis, Tokyo, Japan

[8] Univ Tokyo, Inst Med Sci, Tokyo, Japan

[9] Univ Tokyo, Grad Sch Frontier Sci, Tokyo, Japan

[10] Natl Canc Ctr, Ctr Publ Hlth Sci, Div Epidemiol, Tokyo, Japan

[11] Iwate Med Univ, Iwate Tohoku Med Megabank Org, Morioka, Iwate, Japan

[12] Iwate Med Univ, Sch Med, Dept Hyg & Prevent Med, Morioka, Iwate, Japan

[13] Tohoku Univ, Tohoku Med Megabank Org, Sendai, Miyagi, Japan

[14] Tohoku Univ, Grad Sch Med, Sendai, Miyagi, Japan

[15] Natl Canc Ctr, Ctr Publ Hlth Sci, Tokyo, Japan

[16] RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[17] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan

来源：

NATURE GENETICS | 2017年 / 49卷 / 10期

关键词：

LD SCORE REGRESSION; INSULIN-RESISTANCE; FUNCTIONAL ANNOTATION; RHEUMATOID-ARTHRITIS; GENETIC-VARIATION; OBESITY; METAANALYSIS; RISK; VARIANTS; HERITABILITY;

D O I：

10.1038/ng.3951

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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 x 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 x 10(-5), r(g) = 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.

引用

页码：1458 / +

页数：12

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