title: Gene-based meta-analysis of genome-wide association study data identifies independent single-nucleotide polymorphisms in ANXA6 as being associated with systemic lupus erythematosus in Asian populations.
abstract: OBJECTIVE
  Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants.
  
  
  METHODS
  Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing.
  
  
  RESULTS
  More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously.
  
  
  CONCLUSIONS
  Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes.
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China, and Eye and ENT Hospital of Fudan University, Shanghai, China.
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authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
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authors.lastname: Zhang
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Yan
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authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Jing
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authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Mengbiao
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authors.lastname: Guo
authors.affiliation: Anhui Medical University, China, Hefei, China.
authors.forename: Liangdan
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authors.lastname: Sun
authors.affiliation: Anhui Medical University, China, Hefei, China.
authors.forename: Hai-Feng
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authors.lastname: Pan
authors.affiliation: Chulalongkorn University, Bangkok, Thailand.
authors.forename: Nattiya
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authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Dingge
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authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Shuai
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authors.lastname: Zeng
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Tsz Leung
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authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Chak Sing
authors.initials: CS
authors.lastname: Lau
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
authors.affiliation: Queen Elizabeth Hospital, Hong Kong, China.
authors.forename: Alexander Moon Ho
authors.initials: AM
authors.lastname: Leung
authors.affiliation: Tuen Mun Hospital, Tuen Mun, New Territories, Hong Kong, China.
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Mok
authors.affiliation: Tuen Mun Hospital, Tuen Mun, New Territories, Hong Kong, China.
authors.forename: Sik Nin
authors.initials: SN
authors.lastname: Wong
authors.affiliation: Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.
authors.forename: Ka Wing
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authors.lastname: Lee
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
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authors.initials: MH
authors.lastname: Ho
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
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authors.lastname: Lee
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Brian Hon-Yin
authors.initials: BH
authors.lastname: Chung
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Chun Yin
authors.initials: CY
authors.lastname: Chong
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Raymond Woon Sing
authors.initials: RW
authors.lastname: Wong
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Mo Yin
authors.initials: MY
authors.lastname: Mok
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Wilfred Hing Sang
authors.initials: WH
authors.lastname: Wong
authors.affiliation: Princess Margaret Hospital, Hong Kong, China.
authors.forename: Kwok Lung
authors.initials: KL
authors.lastname: Tong
authors.affiliation: Princess Margaret Hospital, Hong Kong, China.
authors.forename: Niko Kei Chiu
authors.initials: NK
authors.lastname: Tse
authors.affiliation: Anhui Provincial Hospital, Hefei, China.
authors.forename: Xiang-Pei
authors.initials: XP
authors.lastname: Li
authors.affiliation: Chulalongkorn University, Bangkok, Thailand.
authors.forename: Yingyos
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authors.lastname: Avihingsanon
authors.affiliation: Chulalongkorn University, Bangkok, Thailand.
authors.forename: Pornpimol
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authors.affiliation: Chulalongkorn University, Bangkok, Thailand.
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authors.lastname: Deekajorndej
authors.affiliation: Chulalongkorn University, Bangkok, Thailand.
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authors.lastname: Suphapeetiporn
authors.affiliation: Chulalongkorn University, Bangkok, Thailand.
authors.forename: Vorasuk
authors.initials: V
authors.lastname: Shotelersuk
authors.affiliation: Princess Margaret Hospital, Hong Kong, China.
authors.forename: Shirley King Yee
authors.initials: SK
authors.lastname: Ying
authors.affiliation: Princess Margaret Hospital, Hong Kong, China.
authors.forename: Samuel Ka Shun
authors.initials: SK
authors.lastname: Fung
authors.affiliation: Princess Margaret Hospital, Hong Kong, China.
authors.forename: Wai Ming
authors.initials: WM
authors.lastname: Lai
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Maria-Mercè
authors.initials: MM
authors.lastname: Garcia-Barceló
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cherny
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.affiliation: Anhui Medical University, China, Hefei, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Anhui Medical University, China, Hefei, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.affiliation: Anhui Medical University, China, Hefei, China.
authors.forename: Dong Qing
authors.initials: DQ
authors.lastname: Ye
authors.affiliation: Anhui Medical University, China, Hefei, China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China, and The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Queen Mary Hospital and The University of Hong Kong, Hong Kong, China.
authors.forename: Wanling
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mesh_terms: D017317:Annexin A6 / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D017317:Annexin A6