High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry

被引：193

作者：

Sun, Celi ^{[1
]}

Molineros, Julio E. ^{[1
]}

Looger, Loren L. ^{[2
]}

Zhou, Xu-jie ^{[3
,4
]}

Kim, Kwangwoo ^{[5
]}

Okada, Yukinori ^{[6
,7
]}

Ma, Jianyang ^{[8
]}

Qi, Yuan-yuan ^{[3
,4
]}

Kim-Howard, Xana ^{[1
]}

Motghare, Prasenjeet ^{[1
]}

Bhattarai, Krishna ^{[1
]}

Adler, Adam ^{[1
]}

Bang, So-Young ^{[5
]}

Lee, Hye-Soon ^{[5
]}

Kim, Tae-Hwan ^{[5
]}

Kang, Young Mo ^{[9
]}

Suh, Chang-Hee ^{[10
]}

Chung, Won Tae ^{[11
]}

Park, Yong-Beom ^{[12
]}

Choe, Jung-Yoon ^{[13
]}

Shim, Seung Cheol ^{[14
]}

Kochi, Yuta ^{[15
]}

Suzuki, Akari ^{[15
]}

Kubo, Michiaki ^{[16
]}

Sumida, Takayuki ^{[17
]}

Yamamoto, Kazuhiko ^{[15
,18
]}

Lee, Shin-Seok ^{[19
]}

Kim, Young Jin ^{[20
]}

Han, Bok-Ghee ^{[20
]}

Dozmorov, Mikhail ^{[21
]}

Kaufman, Kenneth M. ^{[22
,23
]}

Wren, Jonathan D. ^{[1
]}

Harley, John B. ^{[22
,23
]}

Shen, Nan ^{[8
,24
]}

Chua, Kek Heng ^{[25
]}

Zhang, Hong ^{[3
,4
]}

Bae, Sang-Cheol ^{[5
]}

Nath, Swapan K. ^{[1
]}

机构：

[1] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA

[2] Janelia Res Campus, Howard Hughes Med Inst, Ashburn, VA USA

[3] Peking Univ, Hosp 1, Inst Nephrol, Key Lab Renal Dis,Minist Hlth China,Div Renal, Beijing 100871, Peoples R China

[4] Peking Univ, Minist Educ, Key Lab Chron Kidney Dis Prevent & Treatment, Beijing 100871, Peoples R China

[5] Hanyang Univ, Dept Rheumatol, Hosp Rheumat Dis, Seoul 133791, South Korea

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

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

[8] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Inst Rheumatol, Shanghai 200030, Peoples R China

[9] Kyungpook Natl Univ Hosp, Sch Med, Daegu, South Korea

[10] Ajou Univ Hosp, Dept Rheumatol, Suwon, South Korea

[11] Dong A Univ Hosp, Dept Internal Med, Busan, South Korea

[12] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea

[13] Daegu Catholic Univ Hosp, Dept Internal Med, Daegu, South Korea

[14] Chungnam Natl Univ Hosp, Daejeon Rheumatoid & Degenerat Arthrit Ctr, Daejeon, South Korea

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

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

[17] Univ Tsukuba, Fac Med, Dept Internal Med, Tsukuba, Ibaraki, Japan

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

[19] Chonnam Natl Univ Hosp, Dept Rheumatol, Gwangju, South Korea

[20] Korea Natl Inst Hlth, Osong, South Korea

[21] Virginia Commonwealth Univ, Dept Biostat, Richmond, VA USA

[22] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA

[23] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA

[24] Cincinnati Childrens Hosp Med Ctr, CAGE, Cincinnati, OH 45229 USA

[25] Univ Malaya, Fac Med, Dept Biomed Sci, Kuala Lumpur, Malaysia

来源：

NATURE GENETICS | 2016年 / 48卷 / 03期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; MULTIPLE AUTOIMMUNE-DISEASES; GENOME-WIDE ASSOCIATION; CD226 GLY307SER ASSOCIATION; PRIMARY SJOGRENS-SYNDROME; WILLIAMS-BEUREN SYNDROME; CHINESE HAN POPULATION; TFII-I; SUSCEPTIBILITY LOCI; CLINICAL-FEATURES;

D O I：

10.1038/ng.3496

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,478 SLE cases and 12,656 controls from six East Asian cohorts to identify new SLE susceptibility loci and better localize known loci. We identified ten new loci and confirmed 20 known loci with genome-wide significance. Among the new loci, the most significant locus was GTF2IRDI-GTF21 at 7q11.23 (rs73366469, P-meta = 3.75 x 10(-117), odds ratio (OR) = 2.38), followed by DEF6, IL128, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We identified the most likely functional variants at each locus by analyzing epigenetic marks and gene expression data. Ten candidate variants are known to alter gene expression in cis or in trans. Enrichment analysis highlights the importance of these loci in B cell and T cell biology. The new loci, together with previously known loci, increase the explained heritability of SLE to 24%. The new loci share functional and ontological characteristics with previously reported loci and are possible drug targets for SLE therapeutics.

引用

页码：323 / 330

页数：8

共 46 条

[1] High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry
Celi Sun
Julio E Molineros
Loren L Looger
Xu-jie Zhou
Kwangwoo Kim
Yukinori Okada
Jianyang Ma
Yuan-yuan Qi
Xana Kim-Howard
Prasenjeet Motghare
Krishna Bhattarai
Adam Adler
So-Young Bang
Hye-Soon Lee
Tae-Hwan Kim
Young Mo Kang
Chang-Hee Suh
Won Tae Chung
Yong-Beom Park
Jung-Yoon Choe
Seung Cheol Shim
Yuta Kochi
Akari Suzuki
Michiaki Kubo
Takayuki Sumida
Kazuhiko Yamamoto
Shin-Seok Lee
Young Jin Kim
Bok-Ghee Han
Mikhail Dozmorov
Kenneth M Kaufman
Jonathan D Wren
John B Harley
Nan Shen
Kek Heng Chua
Hong Zhang
Sang-Cheol Bae
Swapan K Nath
Nature Genetics, 2016, 48 : 323 - 330
[2] Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci
Nature Genetics, 2013, 45 : 730 - 738
[3] Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci
Cortes, Adrian
Hadler, Johanna
Pointon, Jenny P.
Robinson, Philip C.
Karaderi, Tugce
Leo, Paul
Cremin, Katie
Pryce, Karena
Harris, Jessica
Lee, Seunghun
Joo, Kyung Bin
Shim, Seung-Cheol
Weisman, Michael
Ward, Michael
Zhou, Xiaodong
Garchon, Henri-Jean
Chiocchia, Gilles
Nossent, Johannes
Lie, Benedicte A.
Forre, Oystein
Tuomilehto, Jaakko
Laiho, Kari
Jiang, Lei
Liu, Yu
Wu, Xin
Bradbury, Linda A.
Elewaut, Dirk
Burgos-Vargas, Ruben
Stebbings, Simon
Appleton, Louise
Farrah, Claire
Lau, Jonathan
Kenna, Tony J.
Haroon, Nigil
Ferreira, Manuel A.
Yang, Jian
Mulero, Juan
Fernandez-Sueiro, Jose Luis
Gonzalez-Gay, Miguel A.
Lopez-Larrea, Carlos
Deloukas, Panos
Donnelly, Peter
Bowness, Paul
Gafney, Karl
Gaston, Hill
Gladman, Dafna D.
Rahman, Proton
Maksymowych, Walter P.
Xu, Huji
Crusius, J. Bart A.
NATURE GENETICS, 2013, 45 (07) : 730 - +
[4] High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci
Kim, Kwangwoo
Bang, So-Young
Lee, Hye-Soon
Cho, Soo-Kyung
Choi, Chan-Bum
Sung, Yoon-Kyoung
Kim, Tae-Hwan
Jun, Jae-Bum
Yoo, Dae Hyun
Kang, Young Mo
Kim, Seong-Kyu
Suh, Chang-Hee
Shim, Seung-Cheol
Lee, Shin-Seok
Lee, Jisoo
Chung, Won Tae
Choe, Jung-Yoon
Shin, Hyoung Doo
Lee, Jong-Young
Han, Bok-Ghee
Nath, Swapan K.
Eyre, Steve
Bowes, John
Pappas, Dimitrios A.
Kremer, Joel M.
Gonzalez-Gay, Miguel A.
Rodriguez-Rodriguez, Luis
Arlestig, Lisbeth
Okada, Yukinori
Diogo, Dorothee
Liao, Katherine P.
Karlson, Elizabeth W.
Raychaudhuri, Soumya
Rantapaa-Dahlqvist, Solbritt
Martin, Javier
Klareskog, Lars
Padyukov, Leonid
Gregersen, Peter K.
Worthington, Jane
Greenberg, Jeffrey D.
Plenge, Robert M.
Bae, Sang-Cheol
ANNALS OF THE RHEUMATIC DISEASES, 2015, 74 (03)
[5] High Density Genotyping Of Immune-Related Disease Genes Identifies 7 New Susceptibility Loci For Behcets Disease
Takeuchi, Masaki
Mizuki, Nobuhisa
Meguro, Akira
Ombrello, Michael J.
Satorius, Colleen
Kirino, Yohei
Kawagoe, Tatsukata
Ustek, Duran
Tugal-tutkun, Ilknur
Seyahi, Emire
Ozyazgan, Yilmaz
Ohno, Shigeaki
Ueda, Atsuhisa
Ishigatsubo, Yoshiaki
Gul, Ahmet
Kastner, Daniel L.
Remmers, Elaine
ARTHRITIS AND RHEUMATISM, 2013, 65 : S721 - S722
[6] Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis
Westerlind, Helga
Mellander, Marie-Rose
Bresso, Francesca
Munch, Andreas
Bonfiglio, Ferdinando
Assadi, Ghazaleh
Rafter, Joseph
Huebenthal, Matthias
Lieb, Wolfgang
Kallberg, Henrik
Brynedal, Boel
Padyukov, Leonid
Halfvarson, Jonas
Torkvist, Leif
Bjork, Jan
Andreasson, Anna
Agreus, Lars
Almer, Sven
Miehlke, Stephan
Madisch, Ahmed
Ohlsson, Bodil
Lofberg, Robert
Hultcrantz, Rolf
Franke, Andre
D'Amato, Mauro
GUT, 2017, 66 (03) : 421 - 428
[7] Accounting For Parental Load and Identification Of Multiple Risk Variants For Anti-Ro Congenital Heart Block Through High-Density Genotyping Of Immune-Related Loci
Clancy, Robert M.
Buyon, Jill P.
Costedoat-Chalumeau, Nathalie
Brucato, Antonio
Levesque, Kateri
Ramoni, Veronique
Marion, Miranda C.
Comeau, Mary
Sajuthi, Satria
Ramos, Paula S.
Kimberly, Robert P.
Howard, Timothy D.
Langefeld, Carl D.
ARTHRITIS AND RHEUMATISM, 2013, 65 : S1226 - S1226
[8] Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis
Liu, Jimmy Z.
Hov, Johannes Roksund
Folseraas, Trine
Ellinghaus, Eva
Rushbrook, Simon M.
Doncheva, Nadezhda T.
Andreassen, Ole A.
Weersma, Rinse K.
Weismueller, Tobias J.
Eksteen, Bertus
Invernizzi, Pietro
Hirschfield, Gideon M.
Gotthardt, Daniel Nils
Pares, Albert
Ellinghaus, David
Shah, Tejas
Juran, Brian D.
Milkiewicz, Piotr
Rust, Christian
Schramm, Christoph
Mueller, Tobias
Srivastava, Brijesh
Dalekos, Georgios
Noethen, Markus M.
Herms, Stefan
Winkelmann, Juliane
Mitrovic, Mitja
Braun, Felix
Ponsioen, Cyriel Y.
Croucher, Peter J. P.
Sterneck, Martina
Teufel, Andreas
Mason, Andrew L.
Saarela, Janna
Leppa, Virpi
Dorfman, Ruslan
Alvaro, Domenico
Floreani, Annarosa
Onengut-Gumuscu, Suna
Rich, Stephen S.
Thompson, Wesley K.
Schork, Andrew J.
Naess, Sigrid
Thomsen, Ingo
Mayr, Gabriele
Koenig, Inke R.
Hveem, Kristian
Cleynen, Isabelle
Gutierrez-Achury, Javier
Ricano-Ponce, Isis
NATURE GENETICS, 2013, 45 (06) : 670 - +
[9] Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis
Jimmy Z Liu
Johannes Roksund Hov
Trine Folseraas
Eva Ellinghaus
Simon M Rushbrook
Nadezhda T Doncheva
Ole A Andreassen
Rinse K Weersma
Tobias J Weismüller
Bertus Eksteen
Pietro Invernizzi
Gideon M Hirschfield
Daniel Nils Gotthardt
Albert Pares
David Ellinghaus
Tejas Shah
Brian D Juran
Piotr Milkiewicz
Christian Rust
Christoph Schramm
Tobias Müller
Brijesh Srivastava
Georgios Dalekos
Markus M Nöthen
Stefan Herms
Juliane Winkelmann
Mitja Mitrovic
Felix Braun
Cyriel Y Ponsioen
Peter J P Croucher
Martina Sterneck
Andreas Teufel
Andrew L Mason
Janna Saarela
Virpi Leppa
Ruslan Dorfman
Domenico Alvaro
Annarosa Floreani
Suna Onengut-Gumuscu
Stephen S Rich
Wesley K Thompson
Andrew J Schork
Sigrid Næss
Ingo Thomsen
Gabriele Mayr
Inke R König
Kristian Hveem
Isabelle Cleynen
Javier Gutierrez-Achury
Isis Ricaño-Ponce
Nature Genetics, 2013, 45 : 670 - 675
[10] Dense Genotyping of Candidate Gene Loci Identifies Variants Associated With High-Density Lipoprotein Cholesterol
Edmondson, Andrew C.
Braund, Peter S.
Stylianou, Ioannis M.
Khera, Amit V.
Nelson, Christopher P.
Wolfe, Megan L.
DerOhannessian, Stephanie L.
Keating, Brendan J.
Qu, Liming
He, Jing
Tobin, Martin D.
Tomaszewski, Maciej
Baumert, Jens
Klopp, Norman
Doering, Angela
Thorand, Barbara
Li, Mingyao
Reilly, Muredach P.
Koenig, Wolfgang
Samani, Nilesh J.
Rader, Daniel J.
CIRCULATION-CARDIOVASCULAR GENETICS, 2011, 4 (02) : 145 - U182

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