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

Masato Akiyama; Yukinori Okada; Masahiro Kanai; Atsushi Takahashi; Yukihide Momozawa; Masashi Ikeda; Nakao Iwata; Shiro Ikegawa; Makoto Hirata; Koichi Matsuda; Motoki Iwasaki; Taiki Yamaji; Norie Sawada; Tsuyoshi Hachiya; Kozo Tanno; Atsushi Shimizu; Atsushi Hozawa; Naoko Minegishi; Shoichiro Tsugane; Masayuki Yamamoto; Michiaki Kubo; Yoichiro Kamatani

doi:10.1038/ng.3951

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

Masato Akiyama, Yukinori Okada, Masahiro Kanai, Atsushi Takahashi, Yukihide Momozawa, Masashi Ikeda, Nakao Iwata, Shiro Ikegawa, Makoto Hirata, Koichi Matsuda, Motoki Iwasaki, Taiki Yamaji, Norie Sawada, Tsuyoshi Hachiya, Kozo Tanno, Atsushi Shimizu, Atsushi Hozawa, Naoko Minegishi, Shoichiro Tsugane, Masayuki YamamotoMichiaki Kubo, Yoichiro Kamatani

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323 Scopus citations

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.

Original language	English
Pages (from-to)	1458-1467
Number of pages	10
Journal	Nature Genetics
Volume	49
Issue number	10
DOIs	https://doi.org/10.1038/ng.3951
State	Published - 1 Oct 2017
Externally published	Yes

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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., ... Kamatani, Y. (2017). Genome-wide association study identifies 112 new loci for body mass index in the Japanese population. Nature Genetics, 49(10), 1458-1467. https://doi.org/10.1038/ng.3951

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

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.",

author = "Masato Akiyama and Yukinori Okada and Masahiro Kanai and Atsushi Takahashi and Yukihide Momozawa and Masashi Ikeda and Nakao Iwata and Shiro Ikegawa and Makoto Hirata and Koichi Matsuda and Motoki Iwasaki and Taiki Yamaji and Norie Sawada and Tsuyoshi Hachiya and Kozo Tanno and Atsushi Shimizu and Atsushi Hozawa and Naoko Minegishi and Shoichiro Tsugane and Masayuki Yamamoto and Michiaki Kubo and Yoichiro Kamatani",

year = "2017",

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doi = "10.1038/ng.3951",

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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 2017, 'Genome-wide association study identifies 112 new loci for body mass index in the Japanese population', Nature Genetics, vol. 49, no. 10, pp. 1458-1467. https://doi.org/10.1038/ng.3951

TY - JOUR

T1 - Genome-wide association study identifies 112 new loci for body mass index in the Japanese population

AU - Akiyama, Masato

AU - Okada, Yukinori

AU - Kanai, Masahiro

AU - Takahashi, Atsushi

AU - Momozawa, Yukihide

AU - Ikeda, Masashi

AU - Iwata, Nakao

AU - Ikegawa, Shiro

AU - Hirata, Makoto

AU - Matsuda, Koichi

AU - Iwasaki, Motoki

AU - Yamaji, Taiki

AU - Sawada, Norie

AU - Hachiya, Tsuyoshi

AU - Tanno, Kozo

AU - Shimizu, Atsushi

AU - Hozawa, Atsushi

AU - Minegishi, Naoko

AU - Tsugane, Shoichiro

AU - Yamamoto, Masayuki

AU - Kubo, Michiaki

AU - Kamatani, Yoichiro

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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.

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JO - Nature Genetics

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

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