Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study

Am J Hum Genet. 2021 Jan 7;108(1):84-99. doi: 10.1016/j.ajhg.2020.11.014. Epub 2020 Dec 11.


Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 × 10-5) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.

Keywords: GWAS; HLA; Takayasu arteritis; chromatin interaction; eQTL; epigenetic; genetic association; genetic risk scroe; vasculitis.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study / methods
  • Humans
  • Inflammatory Bowel Diseases / genetics
  • Male
  • Polymorphism, Single Nucleotide / genetics
  • Takayasu Arteritis / genetics*