title: Identification of susceptibility gene associated with female primary Sjögren's syndrome in Han Chinese by genome-wide association study.
abstract: Primary Sjögren's syndrome (PSS) is an autoimmune disease targeting exocrine glands. It ten times more dominantly affects women than men with an onset peak at menopause. The genetic factor predisposing women to PSS remains unclear. Therefore, we aimed to identify susceptibility loci for PSS in women. We performed genome-wide association study (GWAS) using 242 female PSS patients and 1444 female control in Han Chinese population residing in Taiwan. Replication was conducted in an independent cohort of 178 female PSS and 14,432 control subjects. We identified rs117026326 on GTF2I with GWAS significance (P = 1.10 × 10-15) and rs13079920 on RBMS3 with suggestive significance (P = 2.90 × 10-5) associating with PSS in women. The association of RBMS3 was further evidenced by imputation in which rs13072846 (P = 4.89 × 10-5) was identified and confirmed as female PSS associating SNP within the same LD with rs13079920. PSS pathogenesis involves both immune (effector) and exocrine (target) system. We suggested that while GTF2I is a previously reported associating gene which may function in immune system, RBMS3 is a novel susceptibility gene that predisposes women to PSS potentially through modulating acinar apoptosis and TGF-β signaling in target exocrine system.
authors: National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd. Nankang, Taipei, 11529, Taiwan.
authors: I-Wen
authors: IW
authors: Song
authors: Rheumatology, Immunology and Allergy Division, Tri-Service General Hospital, National Defense Medical Center, Taipei, 11490, Taiwan.
authors: Hsiang-Cheng
authors: HC
authors: Chen
authors: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.|Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, New Taipei, 23561, Taiwan.
authors: Yuh-Feng
authors: YF
authors: Lin
authors: National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd. Nankang, Taipei, 11529, Taiwan.
authors: Jenn-Hwai
authors: JH
authors: Yang
authors: Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, 11031, Taiwan.
authors: Chi-Ching
authors: CC
authors: Chang
authors: Division of Allergy-Immunology-Rheumatology, Veterans General Hospital, Taipei, 11217, Taiwan.
authors: Chung-Tei
authors: CT
authors: Chou
authors: National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd. Nankang, Taipei, 11529, Taiwan.|Genomic Medicine Institute, Geisinger Health System, Danville, PA, 17822, USA.
authors: Ming-Ta Michael
authors: MM
authors: Lee
authors: National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd. Nankang, Taipei, 11529, Taiwan.
authors: Yi-Chun
authors: YC
authors: Chou
authors: National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd. Nankang, Taipei, 11529, Taiwan.|Graduate Institute of Chinese Medical Science, China Medical University, Taichung, 40447, Taiwan.
authors: Chien-Hsiun
authors: CH
authors: Chen
authors: National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd. Nankang, Taipei, 11529, Taiwan.|Department of Pediatrics, Duke University Medical Center, Durham, NC, 27710, USA.
authors: Yuan-Tsong
authors: YT
authors: Chen
authors: Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Taipei Tzu Chi Hospital, No.289, Jianguo Rd., Xindian Dist., New Taipei City, 23142, Taiwan. kasper4730@hotmail.com.|Buddhist Tzu Chi Medical Foundation, School of Medicine, Tzu Chi University, Hualien, 97002, Taiwan. kasper4730@hotmail.com.
authors: Chen-Hung
authors: CH
authors: Chen
authors: National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2, Academia Rd. Nankang, Taipei, 11529, Taiwan. jywu@ibms.sinica.edu.tw.|Graduate Institute of Chinese Medical Science, China Medical University, Taichung, 40447, Taiwan. jywu@ibms.sinica.edu.tw.
authors: Jer-Yuarn
authors: JY
authors: Wu
mesh_terms: D061354:Acinar Cells / Q000378:metabolism; D000328:Adult; D017209:Apoptosis / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics*; D019473:Transcription Factors, TFII / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: C104259:GTF2I protein, human; C405932:RBMS3 protein, human; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D019473:Transcription Factors, TFII; D016212:Transforming Growth Factor beta