Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis.
Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis.
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DOI：
10.1038/s41588-022-01213-w
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发表时间：
2022-11
期刊：
影响因子：
30.8
通讯作者：
Raychaudhuri, Soumya
中科院分区：
文献类型：
--
作者：
Ishigaki, Kazuyoshi;Sakaue, Saori;Terao, Chikashi;Luo, Yang;Sonehara, Kyuto;Yamaguchi, Kensuke;Amariuta, Tiffany;Too, Chun Lai;Laufer, Vincent A.;Scott, Ian C.;Viatte, Sebastien;Takahashi, Meiko;Ohmura, Koichiro;Murasawa, Akira;Hashimoto, Motomu;Ito, Hiromu;Hammoudeh, Mohammed;Al Emadi, Samar;Masri, Basel K.;Halabi, Hussein;Badsha, Humeira;Uthman, Imad W.;Wu, Xin;Lin, Li;Li, Ting;Plant, Darren;Barton, Anne;Orozco, Gisela;Verstappen, Suzanne M. M.;Bowes, John;MacGregor, Alexander J.;Honda, Suguru;Koido, Masaru;Tomizuka, Kohei;Kamatani, Yoichiro;Tanaka, Hiroaki;Tanaka, Eiichi;Suzuki, Akari;Maeda, Yuichi;Yamamoto, Kenichi;Miyawaki, Satoru;Xie, Gang;Zhang, Jinyi;Amos, Christopher, I;Keystone, Edward;Wolbink, Gertjan;Van der Horst-Bruinsma, Irene;Cui, Jing;Liao, Katherine P.;Carroll, Robert J.;Lee, Hye-Soon;Bang, So-Young;Siminovitch, Katherine A.;de Vries, Niek;Alfredsson, Lars;Rantapaa-Dahlqvist, Solbritt;Karlson, Elizabeth W.;Bae, Sang-Cheol;Kimberly, Robert P.;Edberg, Jeffrey C.;Mariette, Xavier;Huizinga, Tom;Dieude, Philippe;Schneider, Matthias;Kerick, Martin;Denny, Joshua C.;Matsuda, Koichi;Matsuo, Keitaro;Mimori, Tsuneyo;Matsuda, Fumihiko;Fujio, Keishi;Tanaka, Yoshiya;Kumanogoh, Atsushi;Traylor, Matthew;Lewis, Cathryn M.;Eyre, Stephen;Xu, Huji;Saxena, Richa;Arayssi, Thurayya;Kochi, Yuta;Ikari, Katsunori;Harigai, Masayoshi;Gregersen, Peter K.;Yamamoto, Kazuhiko;Bridges, S. Louis, Jr.;Padyukov, Leonid;Martin, Javier;Klareskog, Lars;Okada, Yukinori;Raychaudhuri, Soumya
风湿性关节炎（RA）是一种病因不明的高度遗传性复杂疾病。RA的多祖先遗传学研究有望提高遗传信号的检测能力、精细定位的分辨率和多基因风险评分（PRS）的性能。在这里，我们提出了一个大规模的RA全基因组关联研究（GWAS），其中包括来自五个祖先群体的276，020个样本。我们进行了一项多祖先荟萃分析，确定了124个位点（P < 5 × 10−8），其中34个是新的。新基因座的候选基因表明免疫系统（例如TNIP 2和TNFRSF11A）和关节组织（例如WISP 1）在RA病因学中的重要作用。多祖先精细定位确定了具有生物学见解的pupulmonary因果变异（例如，LEF1）。此外，基于多血统GWAS的PRS优于基于单血统GWAS的PRS，并且在欧洲和东亚血统人群之间具有可比性。我们的研究为RA的病因学提供了一些见解，并提高了RA的遗传预测性。
Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10−8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.
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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：
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：
30.8
作者：
Finucane HK;Reshef YA;Anttila V;Slowikowski K;Gusev A;Byrnes A;Gazal S;Loh PR;Lareau C;Shoresh N;Genovese G;Saunders A;Macosko E;Pollack S;Brainstorm Consortium;Perry JRB;Buenrostro JD;Bernstein BE;Raychaudhuri S;McCarroll S;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
3.7
作者：
Diogo D;Bastarache L;Liao KP;Graham RR;Fulton RS;Greenberg JD;Eyre S;Bowes J;Cui J;Lee A;Pappas DA;Kremer JM;Barton A;Coenen MJ;Franke B;Kiemeney LA;Mariette X;Richard-Miceli C;Canhão H;Fonseca JE;de Vries N;Tak PP;Crusius JB;Nurmohamed MT;Kurreeman F;Mikuls TR;Okada Y;Stahl EA;Larson DE;Deluca TL;O'Laughlin M;Fronick CC;Fulton LL;Kosoy R;Ransom M;Bhangale TR;Ortmann W;Cagan A;Gainer V;Karlson EW;Kohane I;Murphy SN;Martin J;Zhernakova A;Klareskog L;Padyukov L;Worthington J;Mardis ER;Seldin MF;Gregersen PK;Behrens T;Raychaudhuri S;Denny JC;Plenge RM
通讯作者：
Plenge RM
影响因子：
4.5
作者：
Ferreira RC;Freitag DF;Cutler AJ;Howson JM;Rainbow DB;Smyth DJ;Kaptoge S;Clarke P;Boreham C;Coulson RM;Pekalski ML;Chen WM;Onengut-Gumuscu S;Rich SS;Butterworth AS;Malarstig A;Danesh J;Todd JA
通讯作者：
Todd JA