Identification of potential genetic causal variants for rheumatoid arthritis by whole-exome sequencing

Ying Li, Elaine Lai Han Leung, Hudan Pan, Xiaojun Yao, Qingchun Huang, Min Wu, Ting Xu, Yuwei Wang, Jun Cai, Runze Li, Wei Liu, Liang Liu

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Rheumatoid arthritis (RA) is a highly prevalent chronic autoimmune disease. However, genetic and environmental factors involved in RA pathogenesis are still remained largely unknown. To identify the genetic causal variants underlying pathogenesis and disease progression of RA patients, we undertook the first comprehensive whole-exome sequencing (WES) study in a total of 124 subjects including 58 RA cases and 66 healthy controls in Han Chinese population. We identified 378 novel genes that were enriched with deleterious variants in RA patients using a gene burden test. The further functional effects of associated genetic genes were classified and assessed, including 21 newly identified genes that were involved in the extracellular matrix (ECM)-receptor interaction, protein digestion and absorption, focal adhesion and glycerophospholipid metabolism pathways relevant to RA pathogenesis. Moreover, six pathogenic variants were investigated and structural analysis predicted their potentially functional alteration by homology modeling. Importantly, five novel and rare homozygous variants (NCR3LG1, RAP1GAP, CHCHD5, HIPK2 and DIAPH2) were identified, which may exhibit more functional impact on RA pathogenesis. Notably, 7 genes involved in the olfactory transduction pathway were enriched and associated with RA disease progression. Therefore, we performed an efficient and powerful technique WES in Chinese RA patients and identifie d novel, rare and common disease causing genes that alter innate immunity pathways and contribute to the risk of RA. Findings in this study may provide potential diagnostic tools and therapeutic strategies for RA patients.

Original languageEnglish (US)
Pages (from-to)111119-111129
Number of pages11
Issue number67
StatePublished - 2017
Externally publishedYes


  • Chinese population
  • Genetic causal variants
  • Homology modeling
  • Rheumatoid arthritis
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Oncology


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