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.
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Key Laboratory of Dermatology, Anhui Medical University, Hefei, China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Zuo
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Key Laboratory of Dermatology, Anhui Medical University, Hefei, China.
authors.forename: Liangdan
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Pan
authors.affiliation: Lupus Research Unit, Department of Microbiology.
authors.forename: Nattiya
authors.initials: N
authors.lastname: Hirankarn
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Tingyou
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Ruoyan
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Dingge
authors.initials: D
authors.lastname: Ying
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Jiangshan Jane
authors.initials: JJ
authors.lastname: Shen
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Tsz Leung
authors.initials: TL
authors.lastname: Lee
authors.affiliation: Department of Medicine.
authors.forename: Chak Sing
authors.initials: CS
authors.lastname: Lau
authors.affiliation: Department of Medicine.
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
authors.affiliation: Department of Medicine, Queen Elizabeth Hospital, Hong Kong.
authors.forename: Alexander Moon Ho
authors.initials: AM
authors.lastname: Leung
authors.affiliation: Department of Medicine and.
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Mok
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Tuen Mun Hospital, Hong Kong.
authors.forename: Sik Nin
authors.initials: SN
authors.lastname: Wong
authors.affiliation: Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong.
authors.forename: Ka Wing
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Marco Hok Kung
authors.initials: MH
authors.lastname: Ho
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Pamela Pui Wah
authors.initials: PP
authors.lastname: Lee
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Brian Hon-Yin
authors.initials: BH
authors.lastname: Chung
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Chun Yin
authors.initials: CY
authors.lastname: Chong
authors.affiliation: Department of Medicine.
authors.forename: Raymond Woon Sing
authors.initials: RW
authors.lastname: Wong
authors.affiliation: Department of Medicine.
authors.forename: Mo Yin
authors.initials: MY
authors.lastname: Mok
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Wilfred Hing Sang
authors.initials: WH
authors.lastname: Wong
authors.affiliation: Department of Medicine and.
authors.forename: Kwok Lung
authors.initials: KL
authors.lastname: Tong
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong and.
authors.forename: Niko Kei Chiu
authors.initials: NK
authors.lastname: Tse
authors.affiliation: Department of Rheumatology, Anhui Provincial Hospital, Hefei, China.
authors.forename: Xiang-Pei
authors.initials: XP
authors.lastname: Li
authors.affiliation: Department of Medicine and.
authors.forename: Yingyos
authors.initials: Y
authors.lastname: Avihingsanon
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Pornpimol
authors.initials: P
authors.lastname: Rianthavorn
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Thavatchai
authors.initials: T
authors.lastname: Deekajorndej
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Kanya
authors.initials: K
authors.lastname: Suphapeetiporn
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Vorasuk
authors.initials: V
authors.lastname: Shotelersuk
authors.affiliation: Department of Medicine and.
authors.forename: Shirley King Yee
authors.initials: SK
authors.lastname: Ying
authors.affiliation: Department of Medicine and.
authors.forename: Samuel Ka Shun
authors.initials: SK
authors.lastname: Fung
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong and.
authors.forename: Wai Ming
authors.initials: WM
authors.lastname: Lai
authors.affiliation: Department of Pathology.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Wong
authors.affiliation: Department of Pathology.
authors.forename: Irene Oi Lin
authors.initials: IO
authors.lastname: Ng
authors.affiliation: Department of Surgery.
authors.forename: Maria-Merce
authors.initials: MM
authors.lastname: Garcia-Barcelo
authors.affiliation: Department of Psychiatry and.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cherny
authors.affiliation: Department of Surgery.
authors.forename: Paul Kwong-Hang
authors.initials: PK
authors.lastname: Tam
authors.affiliation: Department of Psychiatry and Centre for Genomic Sciences, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Key Laboratory of Dermatology, Anhui Medical University, Hefei, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.
authors.forename: Dong Qing
authors.initials: DQ
authors.lastname: Ye
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Key Laboratory of Dermatology, Anhui Medical University, Hefei, China yangwl@hkucc.hku.hk lauylung@hkucc.hku.hk wuhucuiyong@vip.163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory Incubation Base of Dermatology, Key Laboratory of Dermatology, Anhui Medical University, Hefei, China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Department of Paediatrics and Adolescent Medicine yangwl@hkucc.hku.hk lauylung@hkucc.hku.hk wuhucuiyong@vip.163.com.
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Department of Paediatrics and Adolescent Medicine Centre for Genomic Sciences, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong yangwl@hkucc.hku.hk lauylung@hkucc.hku.hk wuhucuiyong@vip.163.com.
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
mesh_terms: D044466:Asian People / Q000235:genetics*; D002681:China; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D050172:Genes, X-Linked; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012268:Ribose-Phosphate Pyrophosphokinase / Q000235:genetics*
chemical_list: C000600435:PRPS2 protein, human; D012268:Ribose-Phosphate Pyrophosphokinase