Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
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DOI：
10.1038/s41588-020-0640-3
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发表时间：
2020-07
期刊：
影响因子：
30.8
通讯作者：
Kamatani Y
中科院分区：
文献类型：
--
作者：
Ishigaki K;Akiyama M;Kanai M;Takahashi A;Kawakami E;Sugishita H;Sakaue S;Matoba N;Low SK;Okada Y;Terao C;Amariuta T;Gazal S;Kochi Y;Horikoshi M;Suzuki K;Ito K;Koyama S;Ozaki K;Niida S;Sakata Y;Sakata Y;Kohno T;Shiraishi K;Momozawa Y;Hirata M;Matsuda K;Ikeda M;Iwata N;Ikegawa S;Kou I;Tanaka T;Nakagawa H;Suzuki A;Hirota T;Tamari M;Chayama K;Miki D;Mori M;Nagayama S;Daigo Y;Miki Y;Katagiri T;Ogawa O;Obara W;Ito H;Yoshida T;Imoto I;Takahashi T;Tanikawa C;Suzuki T;Sinozaki N;Minami S;Yamaguchi H;Asai S;Takahashi Y;Yamaji K;Takahashi K;Fujioka T;Takata R;Yanai H;Masumoto A;Koretsune Y;Kutsumi H;Higashiyama M;Murayama S;Minegishi N;Suzuki K;Tanno K;Shimizu A;Yamaji T;Iwasaki M;Sawada N;Uemura H;Tanaka K;Naito M;Sasaki M;Wakai K;Tsugane S;Yamamoto M;Yamamoto K;Murakami Y;Nakamura Y;Raychaudhuri S;Inazawa J;Yamauchi T;Kadowaki T;Kubo M;Kamatani Y
目前基因研究的绝大多数参与者都是欧洲血统。为了阐明东亚人群中的疾病生物学，我们对42种疾病中的212,453名日本人进行了全基因组关联研究(GWAS)。我们在27种疾病的276个基因座中检测到320个独立信号，其中有25个新基因座(P<；9.58x10−9)。东亚特有的错义变异被确定为三个新基因座的候选因果变异，我们通过分析独立的日本队列成功复制了其中两个：ATG16L2的p.R220W与冠状动脉疾病相关，POT1的p.V326A与肺癌相关。我们进一步研究了2,868个全基因组转录因子占有率注释中的遗传性丰富，并确定了9种疾病(FDR<；0.05)中的378个显著丰富(例如，前列腺癌的NKX3-1)。这项在日本人群中进行的大规模GWAS研究提供了对复杂疾病病因学的洞察，并强调了在非欧洲人群中实施GWA的重要性。
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 (FDR < 0.05) (e.g. 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.
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DOI：
10.1093/bioinformatics/btw112
发表时间：
2016-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Elhanati Y;Marcou Q;Mora T;Walczak AM
通讯作者：
Walczak AM
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ