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Confirmation of five novel susceptibility loci for systemic lupus erythematosus (SLE) and integrated network analysis of 82 SLE susceptibility loci

Molineros JE 1 , Yang W 2 , Zhou XJ 3 , Sun C 1 , Okada Y 4 , Zhang H 2 Show all authors , Heng Chua K 5 , Lau YL 2 , Kochi Y 6 , Suzuki A 6 , Yamamoto K 6 , Ma J 7 , Bang SY 8 , Lee HS 8 , Kim K 9 , Bae SC 8 , Zhang H 3 , Shen N 7 , Looger LL 10 , Nath SK 1

Affiliations 

  • 1 Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA
  • 2 Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
  • 3 Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, and Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China
  • 4 Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan
  • 5 Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 6 Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan
  • 7 Joint Molecular Rheumatology Laboratory of the Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China
  • 8 Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
  • 9 Department of Biology, Kyung Hee University, Seoul 02447, Korea
  • 10 Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
Hum Mol Genet, 2017 03 15;26(6):1205-1216.
PMID: 28108556 DOI: 10.1093/hmg/ddx026

Abstract

We recently identified ten novel SLE susceptibility loci in Asians and uncovered several additional suggestive loci requiring further validation. This study aimed to replicate five of these suggestive loci in a Han Chinese cohort from Hong Kong, followed by meta-analysis (11,656 cases and 23,968 controls) on previously reported Asian and European populations, and to perform bioinformatic analyses on all 82 reported SLE loci to identify shared regulatory signatures. We performed a battery of analyses for these five loci, as well as joint analyses on all 82 SLE loci. All five loci passed genome-wide significance: MYNN (rs10936599, Pmeta = 1.92 × 10-13, OR = 1.14), ATG16L2 (rs11235604, Pmeta = 8.87 × 10 -12, OR = 0.78), CCL22 (rs223881, Pmeta = 5.87 × 10-16, OR = 0.87), ANKS1A (rs2762340, Pmeta = 4.93 × 10-15, OR = 0.87) and RNASEH2C (rs1308020, Pmeta = 2.96 × 10-19, OR = 0.84) and co-located with annotated gene regulatory elements. The novel loci share genetic signatures with other reported SLE loci, including effects on gene expression, transcription factor binding, and epigenetic characteristics. Most (56%) of the correlated (r2 > 0.8) SNPs from the 82 SLE loci were implicated in differential expression (9.81 × 10-198 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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