title: Multiple variants in 5q31.1 are associated with systemic lupus erythematosus susceptibility and subphenotypes in the Han Chinese population.
abstract: BACKGROUND
  A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi-ancestral cohorts, but failed to find significant evidence for an association in the Han Chinese population.
  
  
  OBJECTIVE
  To explore the association between this locus and SLE using data from our previously published genome-wide association study (GWAS).
  
  
  METHODS
  Single-nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31.1) were selected as candidate independent associations from a large-scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells.
  
  
  RESULTS
  Highly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P = 0·001). The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased compared with those in healthy controls.
  
  
  CONCLUSIONS
  This study found evidence for multiple associations with SLE in 5q31.1 at genome-wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE.
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: L L
authors.initials: LL
authors.lastname: Wen
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: Z W
authors.initials: ZW
authors.lastname: Zhu
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: X B
authors.initials: XB
authors.lastname: Zuo
authors.affiliation: Division of Genetics and Molecular Medicine, King's College London, U.K.
authors.forename: D L
authors.initials: DL
authors.lastname: Morris
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: J F
authors.initials: JF
authors.lastname: Dou
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: L
authors.initials: L
authors.lastname: Ye
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Cheng
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: H M
authors.initials: HM
authors.lastname: Guo
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: H Q
authors.initials: HQ
authors.lastname: Huang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.|Department of Dermatology, the Fourth Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: C H
authors.initials: CH
authors.lastname: Zhu
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: L L
authors.initials: LL
authors.lastname: Tang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: M Y
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: Y T
authors.initials: YT
authors.lastname: Ding
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: B
authors.initials: B
authors.lastname: Liang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: F S
authors.initials: FS
authors.lastname: Zhou
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: J P
authors.initials: JP
authors.lastname: Gao
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: X F
authors.initials: XF
authors.lastname: Tang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: X D
authors.initials: XD
authors.lastname: Zheng
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: W J
authors.initials: WJ
authors.lastname: Wang
authors.affiliation: Department of Genetics, and Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, U.S.A.
authors.forename: X Y
authors.initials: XY
authors.lastname: Yin
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Tang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: L D
authors.initials: LD
authors.lastname: Sun
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: X J
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China.|Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, 230032, China.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Sheng
authors.affiliation: Department of Dermatology, China-Japan Friendship Hospital, East Street Cherry Park, Chaoyang District, Beijing, 100029, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cui
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051822:T Cell Transcription Factor 1 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2