A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis Academic Article uri icon


MeSH Major

  • Alleles
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study
  • Giant Cell Arteritis
  • Plasminogen
  • Prolyl Hydroxylases


  • Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10(-54), per-allele OR = 1.79; and rs9275592, p = 1.14 × 10(-40), OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10(-10), OR = 1.28; and rs128738, p = 4.60 × 10(-9), OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis.


publication date

  • January 5, 2017



  • Academic Article



  • eng

PubMed Central ID

  • PMC5223025

Digital Object Identifier (DOI)

  • 10.1016/j.ajhg.2016.11.013

PubMed ID

  • 28041642

Additional Document Info

start page

  • 64

end page

  • 74


  • 100


  • 1