Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases

被引：300

作者：

Ishigaki, Kazuyoshi ^{[1
,2
,3
,4
,5
]}

Akiyama, Masato ^{[1
,6
]}

Kanai, Masahiro ^{[1
,5
,7
]}

Takahashi, Atsushi ^{[1
,8
]}

Kawakami, Eiryo ^{[9
,10
,11
]}

Sugishita, Hiroki ^{[10
]}

Sakaue, Saori ^{[1
,12
,13
]}

Matoba, Nana ^{[1
,14
,15
]}

Low, Siew-Kee ^{[1
,16
]}

Okada, Yukinori ^{[1
,12
,17
,18
]}

Terao, Chikashi ^{[19
]}

Amariuta, Tiffany ^{[2
,3
,4
,5
,7
,20
]}

Gazal, Steven ^{[5
,21
]}

Kochi, Yuta ^{[22
,23
]}

Horikoshi, Momoko ^{[24
]}

Suzuki, Ken ^{[1
,12
,24
,25
]}

Ito, Kaoru ^{[26
]}

Koyama, Satoshi ^{[26
]}

Ozaki, Kouichi ^{[27
]}

Niida, Shumpei ^{[27
]}

Sakata, Yasushi ^{[28
]}

Sakata, Yasuhiko ^{[29
]}

Kohno, Takashi ^{[9
]}

Shiraishi, Kouya ^{[30
]}

Momozawa, Yukihide ^{[31
]}

Hirata, Makoto ^{[32
]}

Matsuda, Koichi ^{[33
]}

Ikeda, Masashi ^{[34
]}

Iwata, Nakao ^{[34
]}

Ikegawa, Shiro ^{[35
]}

Kou, Ikuyo ^{[35
]}

Tanaka, Toshihiro ^{[36
,37
]}

Nakagawa, Hidewaki ^{[38
]}

Suzuki, Akari ^{[22
]}

Hirota, Tomomitsu ^{[39
]}

Tamari, Mayumi ^{[39
]}

Chayama, Kazuaki ^{[40
]}

Miki, Daiki ^{[40
]}

Mori, Masaki ^{[41
]}

Nagayama, Satoshi ^{[42
]}

Daigo, Yataro ^{[43
,44
,45
,46
]}

Miki, Yoshio ^{[47
]}

Katagiri, Toyomasa ^{[48
]}

Ogawa, Osamu ^{[49
]}

Obara, Wataru ^{[50
]}

Ito, Hidemi ^{[51
,52
]}

Yoshida, Teruhiko ^{[53
]}

Imoto, Issei ^{[54
,55
,56
]}

Takahashi, Takashi ^{[57
]}

Tanikawa, Chizu ^{[58
]}

机构：

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

[2] Harvard Med Sch, Ctr Data Sci, Boston, MA 02115 USA

[3] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA

[4] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02115 USA

[5] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA

[6] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Japan

[7] Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA

[8] Natl Cerebral & Cardiovasc Ctr, Res Inst, Dept Genom Med, Osaka, Japan

[9] RIKEN, Med Sci Innovat Hub Program MIH, Yokohama, Kanagawa, Japan

[10] RIKEN Ctr Integrat Med Sci, Lab Dev Genet, Yokohama, Kanagawa, Japan

[11] Chiba Univ, Grad Sch Med, Artificial Intelligence Med, Chiba, Japan

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

[13] Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Tokyo, Japan

[14] Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA

[15] Univ N Carolina, UNC Neurosci Ctr, Chapel Hill, NC 27515 USA

[16] Japanese Fdn Canc Res, Canc Precis Med Ctr, Tokyo, Japan

[17] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Stat Immunol, Osaka, Japan

[18] Osaka Univ, Inst Open & Transdisciplinary Res Initiat, Integrated Frontier Res Med Sci Div, Osaka, Japan

[19] RIKEN Ctr Integrat Med Sci, Lab Stat & Translat Genet, Yokohama, Kanagawa, Japan

[20] Harvard Univ, Grad Sch Arts & Sci, Cambridge, MA 02138 USA

[21] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[22] RIKEN Ctr Integrat Med Sci, Lab Autoimmune Dis, Yokohama, Kanagawa, Japan

[23] Tokyo Med & Dent Univ, Med Res Inst, Dept Genom Funct & Divers, Tokyo, Japan

[24] RIKEN Ctr Integrat Med Sci, Lab Genom Diabet & Metab, Yokohama, Kanagawa, Japan

[25] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo, Japan

[26] RIKEN Ctr Integrat Med Sci, Lab Cardiovasc Genom & Informat, Yokohama, Kanagawa, Japan

[27] Natl Ctr Geriatr & Gerontol, Med Genome Ctr, Obu, Japan

[28] Osaka Univ, Dept Cardiovasc Med, Grad Sch Med, Osaka, Japan

[29] Tohoku Univ, Dept Cardiovasc Med, Grad Sch Med, Tohoku, Japan

[30] Natl Canc Ctr, Div Genome Biol, Res Inst, Tokyo, Japan

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

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

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

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

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

[36] RIKEN Ctr Integrat Med Sci, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan

[37] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Human Genet & Dis Divers, Tokyo, Japan

[38] RIKEN Ctr Integrat Med Sci, Lab Genome Sequencing Anal, Tokyo, Japan

[39] RIKEN Ctr Integrat Med Sci, Lab Resp & Allerg Dis, Yokohama, Kanagawa, Japan

[40] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Gastroenterol & Metab, Hiroshima, Japan

[41] Kyushu Univ, Grad Sch Med, Dept Surg & Sci, Fukuoka, Japan

[42] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Gastroenterol Surg, Tokyo, Japan

[43] Shiga Univ Med Sci, Dept Med Oncol, Otsu, Shiga, Japan

[44] Shiga Univ Med Sci, Canc Ctr, Otsu, Shiga, Japan

[45] Shiga Univ Med Sci, Ctr Adv Med Canc, Otsu, Shiga, Japan

[46] Univ Tokyo, Res Hosp, Ctr Antibody & Vaccine Therapy, Inst Med Sci, Tokyo, Japan

[47] Japanese Fdn Canc Res, Canc Inst, Dept Genet Diag, Tokyo, Japan

[48] Tokushima Univ, Inst Genome Res, Div Genome Med, Tokushima, Japan

[49] Kyoto Univ, Dept Urol, Grad Sch Med, Kyoto, Japan

[50] Iwate Med Univ, Dept Urol, Sch Med, Morioka, Iwate, Japan

来源：

NATURE GENETICS | 2020年 / 52卷 / 07期

基金：

日本学术振兴会;

关键词：

TRANSCRIPTION FACTOR; GENE; COMMON; RISK; VARIANT; ARCHITECTURE; EXPRESSION; PROJECT; DESIGN; SCORE;

D O I：

10.1038/s41588-020-0640-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.58 x 10(-9)). East Asian-specific missense variants were identified as candidate causal variants for three novel loci, and we successfully replicated two of them by analyzing independent Japanese cohorts; p.R220W of ATG16L2 (associated with coronary artery disease) and p.V326A of POT1 (associated with lung cancer). We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, and identified 378 significant enrichments across nine diseases (false discovery rate < 0.05) (for example, NKX3-1 for prostate cancer). This large-scale GWAS in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations. Genome-wide analysis in 212,453 Japanese individuals identifies loci associated with 42 diseases. Comparative analysis with European populations identifies East Asian-specific associations.

引用

页码：669 / +

页数：24

共 50 条

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