Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians

Am J Hum Genet. 2013 Jan 10;92(1):41-51. doi: 10.1016/j.ajhg.2012.11.018. Epub 2012 Dec 27.


Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • B7-1 Antigen / genetics*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics*
  • DNA-Binding Proteins / genetics*
  • Dioxygenases / genetics*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Lupus Erythematosus, Systemic / ethnology
  • Lupus Erythematosus, Systemic / genetics*
  • Membrane Proteins
  • Polymorphism, Single Nucleotide
  • Proteins / genetics*
  • Transcription Factors / genetics*


  • ARID5B protein, human
  • B7-1 Antigen
  • DNA-Binding Proteins
  • DRAM1 protein, human
  • Membrane Proteins
  • Proteins
  • Transcription Factors
  • Cyclin-Dependent Kinase Inhibitor p27
  • TET3 protein, human
  • Dioxygenases