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Article: Meta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus

TitleMeta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus
Authors
Issue Date2015
Citation
Human Molecular Genetics, 2015, v. 24, n. 1, p. 274-284 How to Cite?
Abstract© The Author 2014. Published by Oxford University Press. All rights reserved. Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects mainly females. What role the X chromosome plays in the disease has always been an intriguing question. In this study, we examined the genetic variants on the X chromosome through meta-analysis of two genome-wide association studies (GWAS) on SLE on Chinese Han populations. Prominent association signals from the meta-analysis were replicated in 4 additional Asian cohorts, with a total of 5373 cases and 9166 matched controls. We identified a novel variant in PRPS2 on Xp22.3 as associated with SLE with genome-wide significance (rs7062536, OR = 0.84, P = 1.00E-08). Association of the L1CAM-MECP2 region with SLE was reported previously. In this study, we identified independent contributors in this region in NAA10 (rs2071128, OR = 0.81, P = 2.19E-13) and TMEM187 (rs17422, OR = 0.75, P = 1.47E-15), in addition to replicating the association from IRAK1-MECP2 region (rs1059702, OR = 0.71, P = 2.40E-18) in Asian cohorts. The X-linked susceptibility variants showed higher effect size in males than that in females, similar to results from a genome-wide survey of associated SNPs on the autosomes. These results suggest that susceptibility genes identified on the X chromosome, while contributing to disease predisposition, might not contribute significantly to the female predominance of this prototype autoimmune disease.
Persistent Identifierhttp://hdl.handle.net/10722/220734
ISSN
2015 Impact Factor: 5.985
2015 SCImago Journal Rankings: 4.288
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Yan-
dc.contributor.authorZhang, Jing-
dc.contributor.authorYang, Jing-
dc.contributor.authorWang, Yongfei-
dc.contributor.authorZhang, Lu-
dc.contributor.authorZuo, Xianbo-
dc.contributor.authorSun, Liangdan-
dc.contributor.authorPan, Hai Feng-
dc.contributor.authorHirankarn, Nattiya-
dc.contributor.authorWang, Tingyou-
dc.contributor.authorChen, Ruoyan-
dc.contributor.authorYing, Dingge-
dc.contributor.authorZeng, Shuai-
dc.contributor.authorShen, Jiangshan Jane-
dc.contributor.authorLee, Tsz Leung-
dc.contributor.authorLau, Chak Sing-
dc.contributor.authorChan, Tak Mao-
dc.contributor.authorLeung, Alexander Moon Ho-
dc.contributor.authorMok, Chi Chiu-
dc.contributor.authorWong, Sik Nin-
dc.contributor.authorLee, Ka Wing-
dc.contributor.authorHo, Marco Hok Kung-
dc.contributor.authorLee, Pamela Pui Wah-
dc.contributor.authorChung, Brian Hon Yin-
dc.contributor.authorChong, Chun Yin-
dc.contributor.authorWong, Raymond Woon Sing-
dc.contributor.authorMok, Mo Yin-
dc.contributor.authorWong, Wilfred Hing Sang-
dc.contributor.authorTong, Kwok Lung-
dc.contributor.authorTse, Niko Kei Chiu-
dc.contributor.authorLi, Xiang Pei-
dc.contributor.authorAvihingsanon, Yingyos-
dc.contributor.authorRianthavorn, Pornpimol-
dc.contributor.authorDeekajorndej, Thavatchai-
dc.contributor.authorSuphapeetiporn, Kanya-
dc.contributor.authorShotelersuk, Vorasuk-
dc.contributor.authorYing, Shirley King Yee-
dc.contributor.authorFung, Samuel Ka Shun-
dc.contributor.authorLai, Wai Ming-
dc.contributor.authorWong, Chun Ming-
dc.contributor.authorNg, Irene Oi Lin-
dc.contributor.authorGarcia-Barcelo, Maria Merce-
dc.contributor.authorCherny, Stacey S.-
dc.contributor.authorTam, Paul Kwong Hang-
dc.contributor.authorSham, Pak Chung-
dc.contributor.authorYang, Sen-
dc.contributor.authorYe, Dong Qing-
dc.contributor.authorCui, Yong-
dc.contributor.authorZhang, Xue Jun-
dc.contributor.authorLau, Yu Lung-
dc.contributor.authorYang, Wanling-
dc.date.accessioned2015-10-16T06:50:24Z-
dc.date.available2015-10-16T06:50:24Z-
dc.date.issued2015-
dc.identifier.citationHuman Molecular Genetics, 2015, v. 24, n. 1, p. 274-284-
dc.identifier.issn0964-6906-
dc.identifier.urihttp://hdl.handle.net/10722/220734-
dc.description.abstract© The Author 2014. Published by Oxford University Press. All rights reserved. Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects mainly females. What role the X chromosome plays in the disease has always been an intriguing question. In this study, we examined the genetic variants on the X chromosome through meta-analysis of two genome-wide association studies (GWAS) on SLE on Chinese Han populations. Prominent association signals from the meta-analysis were replicated in 4 additional Asian cohorts, with a total of 5373 cases and 9166 matched controls. We identified a novel variant in PRPS2 on Xp22.3 as associated with SLE with genome-wide significance (rs7062536, OR = 0.84, P = 1.00E-08). Association of the L1CAM-MECP2 region with SLE was reported previously. In this study, we identified independent contributors in this region in NAA10 (rs2071128, OR = 0.81, P = 2.19E-13) and TMEM187 (rs17422, OR = 0.75, P = 1.47E-15), in addition to replicating the association from IRAK1-MECP2 region (rs1059702, OR = 0.71, P = 2.40E-18) in Asian cohorts. The X-linked susceptibility variants showed higher effect size in males than that in females, similar to results from a genome-wide survey of associated SNPs on the autosomes. These results suggest that susceptibility genes identified on the X chromosome, while contributing to disease predisposition, might not contribute significantly to the female predominance of this prototype autoimmune disease.-
dc.languageeng-
dc.relation.ispartofHuman Molecular Genetics-
dc.titleMeta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1093/hmg/ddu429-
dc.identifier.pmid25149475-
dc.identifier.scopuseid_2-s2.0-84922568081-
dc.identifier.hkuros242450-
dc.identifier.volume24-
dc.identifier.issue1-
dc.identifier.spage274-
dc.identifier.epage284-
dc.identifier.eissn1460-2083-
dc.identifier.isiWOS:000350135400022-

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