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

Yan Zhang; Jing Zhang; Jing Yang; Yongfei Wang; Lu Zhang; Xianbo Zuo; Liangdan Sun; Hai Feng Pan; Nattiya Hirankarn; Tingyou Wang; Ruoyan Chen; Dingge Ying; Shuai Zeng; Jiangshan Jane Shen; Tsz Leung Lee; Chak Sing Lau; Tak Mao Chan; Alexander Moon Ho Leung; Chi Chiu Mok; Sik Nin Wong; Ka Wing Lee; Marco Hok Kung Ho; Pamela Pui Wah Lee; Brian Hon Yin Chung; Chun Yin Chong; Raymond Woon Sing Wong; Mo Yin Mok; Wilfred Hing Sang Wong; Kwok Lung Tong; Niko Kei Chiu Tse; Xiang Pei Li; Yingyos Avihingsanon; Pornpimol Rianthavorn; Thavatchai Deekajorndej; Kanya Suphapeetiporn; Vorasuk Shotelersuk; Shirley King Yee Ying; Samuel Ka Shun Fung; Wai Ming Lai; Chun Ming Wong; Irene Oi Lin Ng; Maria Merce Garcia-Barcelo; Stacey S. Cherny; Paul Kwong Hang Tam; Pak Chung Sham; Sen Yang; Dong Qing Ye; Yong Cui; Xue Jun Zhang; Yu Lung Lau; Wanling Yang

doi:10.1093/hmg/ddu429

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

Yan Zhang, Jing Zhang, Jing Yang, Yongfei Wang, Lu Zhang, Xianbo Zuo, Liangdan Sun, Hai Feng Pan, Nattiya Hirankarn, Tingyou Wang, Ruoyan Chen, Dingge Ying, Shuai Zeng, Jiangshan Jane Shen, Tsz Leung Lee, Chak Sing Lau, Tak Mao Chan, Alexander Moon Ho Leung, Chi Chiu Mok, Sik Nin WongKa Wing Lee, Marco Hok Kung Ho, Pamela Pui Wah Lee, Brian Hon Yin Chung, Chun Yin Chong, Raymond Woon Sing Wong, Mo Yin Mok, Wilfred Hing Sang Wong, Kwok Lung Tong, Niko Kei Chiu Tse, Xiang Pei Li, Yingyos Avihingsanon, Pornpimol Rianthavorn, Thavatchai Deekajorndej, Kanya Suphapeetiporn, Vorasuk Shotelersuk, Shirley King Yee Ying, Samuel Ka Shun Fung, Wai Ming Lai, Chun Ming Wong, Irene Oi Lin Ng, Maria Merce Garcia-Barcelo, Stacey S. Cherny, Paul Kwong Hang Tam, Pak Chung Sham, Sen Yang, Dong Qing Ye, Yong Cui, Xue Jun Zhang, Yu Lung Lau, Wanling Yang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	ddu429
Pages (from-to)	274-284
Number of pages	11
Journal	Human Molecular Genetics
Volume	24
Issue number	1
DOIs	https://doi.org/10.1093/hmg/ddu429
State	Published - 1 Jan 2015
Externally published	Yes

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Zhang, Y., Zhang, J., Yang, J., Wang, Y., Zhang, L., Zuo, X., Sun, L., Pan, H. F., Hirankarn, N., Wang, T., Chen, R., Ying, D., Zeng, S., Shen, J. J., Lee, T. L., Lau, C. S., Chan, T. M., Leung, A. M. H., Mok, C. C., ... Yang, W. (2015). Meta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus. Human Molecular Genetics, 24(1), 274-284. Article ddu429. https://doi.org/10.1093/hmg/ddu429

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

abstract = "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.",

author = "Yan Zhang and Jing Zhang and Jing Yang and Yongfei Wang and Lu Zhang and Xianbo Zuo and Liangdan Sun and Pan, {Hai Feng} and Nattiya Hirankarn and Tingyou Wang and Ruoyan Chen and Dingge Ying and Shuai Zeng and Shen, {Jiangshan Jane} and Lee, {Tsz Leung} and Lau, {Chak Sing} and Chan, {Tak Mao} and Leung, {Alexander Moon Ho} and Mok, {Chi Chiu} and Wong, {Sik Nin} and Lee, {Ka Wing} and Ho, {Marco Hok Kung} and Lee, {Pamela Pui Wah} and Chung, {Brian Hon Yin} and Chong, {Chun Yin} and Wong, {Raymond Woon Sing} and Mok, {Mo Yin} and Wong, {Wilfred Hing Sang} and Tong, {Kwok Lung} and Tse, {Niko Kei Chiu} and Li, {Xiang Pei} and Yingyos Avihingsanon and Pornpimol Rianthavorn and Thavatchai Deekajorndej and Kanya Suphapeetiporn and Vorasuk Shotelersuk and Ying, {Shirley King Yee} and Fung, {Samuel Ka Shun} and Lai, {Wai Ming} and Wong, {Chun Ming} and Ng, {Irene Oi Lin} and Garcia-Barcelo, {Maria Merce} and Cherny, {Stacey S.} and Tam, {Paul Kwong Hang} and Sham, {Pak Chung} and Sen Yang and Ye, {Dong Qing} and Yong Cui and Zhang, {Xue Jun} and Lau, {Yu Lung} and Wanling Yang",

year = "2015",

month = jan,

day = "1",

doi = "10.1093/hmg/ddu429",

language = "אנגלית",

volume = "24",

pages = "274--284",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "1",

}

Zhang, Y, Zhang, J, Yang, J, Wang, Y, Zhang, L, Zuo, X, Sun, L, Pan, HF, Hirankarn, N, Wang, T, Chen, R, Ying, D, Zeng, S, Shen, JJ, Lee, TL, Lau, CS, Chan, TM, Leung, AMH, Mok, CC, Wong, SN, Lee, KW, Ho, MHK, Lee, PPW, Chung, BHY, Chong, CY, Wong, RWS, Mok, MY, Wong, WHS, Tong, KL, Tse, NKC, Li, XP, Avihingsanon, Y, Rianthavorn, P, Deekajorndej, T, Suphapeetiporn, K, Shotelersuk, V, Ying, SKY, Fung, SKS, Lai, WM, Wong, CM, Ng, IOL, Garcia-Barcelo, MM, Cherny, SS, Tam, PKH, Sham, PC, Yang, S, Ye, DQ, Cui, Y, Zhang, XJ, Lau, YL & Yang, W 2015, 'Meta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus', Human Molecular Genetics, vol. 24, no. 1, ddu429, pp. 274-284. https://doi.org/10.1093/hmg/ddu429

TY - JOUR

T1 - Meta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus

AU - Zhang, Yan

AU - Zhang, Jing

AU - Yang, Jing

AU - Wang, Yongfei

AU - Zhang, Lu

AU - Zuo, Xianbo

AU - Sun, Liangdan

AU - Pan, Hai Feng

AU - Hirankarn, Nattiya

AU - Wang, Tingyou

AU - Chen, Ruoyan

AU - Ying, Dingge

AU - Zeng, Shuai

AU - Shen, Jiangshan Jane

AU - Lee, Tsz Leung

AU - Lau, Chak Sing

AU - Chan, Tak Mao

AU - Leung, Alexander Moon Ho

AU - Mok, Chi Chiu

AU - Wong, Sik Nin

AU - Lee, Ka Wing

AU - Ho, Marco Hok Kung

AU - Lee, Pamela Pui Wah

AU - Chung, Brian Hon Yin

AU - Chong, Chun Yin

AU - Wong, Raymond Woon Sing

AU - Mok, Mo Yin

AU - Wong, Wilfred Hing Sang

AU - Tong, Kwok Lung

AU - Tse, Niko Kei Chiu

AU - Li, Xiang Pei

AU - Avihingsanon, Yingyos

AU - Rianthavorn, Pornpimol

AU - Deekajorndej, Thavatchai

AU - Suphapeetiporn, Kanya

AU - Shotelersuk, Vorasuk

AU - Ying, Shirley King Yee

AU - Fung, Samuel Ka Shun

AU - Lai, Wai Ming

AU - Wong, Chun Ming

AU - Ng, Irene Oi Lin

AU - Garcia-Barcelo, Maria Merce

AU - Cherny, Stacey S.

AU - Tam, Paul Kwong Hang

AU - Sham, Pak Chung

AU - Yang, Sen

AU - Ye, Dong Qing

AU - Cui, Yong

AU - Zhang, Xue Jun

AU - Lau, Yu Lung

AU - Yang, Wanling

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

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DO - 10.1093/hmg/ddu429

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SN - 0964-6906

VL - 24

SP - 274

EP - 284

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 1

M1 - ddu429

ER -

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

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