title: Three SNPs in chromosome 11q23.3 are independently associated with systemic lupus erythematosus in Asians.
abstract: Systemic lupus erythematosus (SLE) has a complex etiology and is affected by both genetic and environmental factors. Although more than 40 loci have shown robust association with SLE, the details of these loci, such as the independent contributors and the genes involved, are still unclear. In this study, we performed meta-analysis of two existing genome-wide association studies (GWASs) on Chinese Han populations from Hong Kong and Anhui, China, and followed the findings by further replication on three additional Chinese and Thailand cohorts with a total of 4254 cases and 6262 controls matched geographically and ethnically. We discovered multiple susceptibility variants for SLE in the 11q23.3 region, including variants in/near PHLDB1 (rs11603023, P(_combined) = 1.25E-08, OR = 1.20), DDX6 (rs638893, P(_combined) = 5.19E-07, OR = 1.22) and CXCR5 (rs10892301, P(_combined) = 2.51E-08, OR = 0.85). Genetic contributions from the newly identified variants were all independent of SNP rs4639966, whose association was reported from the previous GWAS. In addition, the three newly identified variants all showed independent association with the disease through modeling by both stepwise and conditional logistic regression. The presence of multiple independent variants in this region emphasizes its role in SLE susceptibility, and also hints the possibility that distinct biological mechanisms might be involved in the disease involving this genomic region.
authors.affiliation: Department of Paediatrics and Adolescent Medicine.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Liangdan
authors.initials: L
authors.lastname: Sun
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Pan
authors.forename: Nattiya
authors.initials: N
authors.lastname: Hirankarn
authors.forename: Dingge
authors.initials: D
authors.lastname: Ying
authors.forename: Shuai
authors.initials: S
authors.lastname: Zeng
authors.forename: Tsz Leung
authors.initials: TL
authors.lastname: Lee
authors.forename: Chak Sing
authors.initials: CS
authors.lastname: Lau
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
authors.forename: Alexander Moon Ho
authors.initials: AM
authors.lastname: Leung
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Mok
authors.forename: Sik Nin
authors.initials: SN
authors.lastname: Wong
authors.forename: Ka Wing
authors.initials: KW
authors.lastname: Lee
authors.forename: Marco Hok Kung
authors.initials: MH
authors.lastname: Ho
authors.forename: Pamela Pui Wah
authors.initials: PP
authors.lastname: Lee
authors.forename: Brian Hon-Yin
authors.initials: BH
authors.lastname: Chung
authors.forename: Chun Yin
authors.initials: CY
authors.lastname: Chong
authors.forename: Raymond Woon Sing
authors.initials: RW
authors.lastname: Wong
authors.forename: Mo Yin
authors.initials: MY
authors.lastname: Mok
authors.forename: Wilfred Hing Sang
authors.initials: WH
authors.lastname: Wong
authors.forename: Kwok Lung
authors.initials: KL
authors.lastname: Tong
authors.forename: Niko Kei Chiu
authors.initials: NK
authors.lastname: Tse
authors.forename: Xiang-Pei
authors.initials: XP
authors.lastname: Li
authors.forename: Yingyos
authors.initials: Y
authors.lastname: Avihingsanon
authors.forename: Pornpimol
authors.initials: P
authors.lastname: Rianthavorn
authors.forename: Thavatchai
authors.initials: T
authors.lastname: Deekajorndej
authors.forename: Kanya
authors.initials: K
authors.lastname: Suphapeetiporn
authors.forename: Vorasuk
authors.initials: V
authors.lastname: Shotelersuk
authors.forename: Shirley King Yee
authors.initials: SK
authors.lastname: Ying
authors.forename: Samuel Ka Shun
authors.initials: SK
authors.lastname: Fung
authors.forename: Wai Ming
authors.initials: WM
authors.lastname: Lai
authors.forename: Maria-Mercè
authors.initials: MM
authors.lastname: Garcia-Barceló
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cherny
authors.forename: Paul Kwong-Hang
authors.initials: PK
authors.lastname: Tam
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.forename: Dong Qing
authors.initials: DQ
authors.lastname: Ye
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002880:Chromosomes, Human, Pair 11; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D054380:Receptors, CXCR5 / Q000235:genetics*
chemical_list: C095085:CXCR5 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C487973:PHLDB1 protein, human; D011518:Proto-Oncogene Proteins; D054380:Receptors, CXCR5; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases