September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Investigation into the genetic architecture of Giant Cell Arteritis through a genome-wide association study.
Author Affiliations & Notes
  • Elisabeth De Smit
    Ophthalmology, Centre for Eye Research Australia, Melbourne, Victoria, Australia
  • Catherine Hill
    Rheumatology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia
  • Tony Merriman
    Biochemistry, University of Otago, Dunedin, New Zealand
  • Katie Cremin
    Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia
  • Paul Leo
    Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia
  • Penny McKelvie
    Pathology, St Vincent's Hospital, Melbourne, Victoria, Australia
  • David Evans
    Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia
  • Matt A Brown
    Diamantina Institute, University of Queensland, Brisbane, Queensland, Australia
  • Alex W Hewitt
    Ophthalmology, Centre for Eye Research Australia, Melbourne, Victoria, Australia
    School of Medicine, Menzies Research Institute Tasmania (University of Tasmania), Hobart, Tasmania, Australia
  • Footnotes
    Commercial Relationships   Elisabeth De Smit, None; Catherine Hill, None; Tony Merriman, None; Katie Cremin, None; Paul Leo, None; Penny McKelvie, None; David Evans, None; Matt Brown, None; Alex Hewitt, None
  • Footnotes
    Support  NHMRC grant 1068023
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6574. doi:
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      Elisabeth De Smit, Catherine Hill, Tony Merriman, Katie Cremin, Paul Leo, Penny McKelvie, David Evans, Matt A Brown, Alex W Hewitt; Investigation into the genetic architecture of Giant Cell Arteritis through a genome-wide association study.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6574.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Giant Cell Arteritis (GCA) is the most common systemic inflammatory vasculitis in people aged over 50 years. It predominantly affects people of Northern European decent and women more than men. It is an ophthalmic emergency and timely diagnosis may prevent significant visual morbidity. The gold standard to diagnose GCA is with a temporal artery biopsy (TAB). To date little is known about the patho-aetiology of GCA. Although there is clear evidence for a role of genetic factors in GCA, genetic studies have been limited in view of the demographic involved, its relatively low incidence rate and the resulting challenge of recruiting an adequately large number of patients. The aim of this work is to investigate the genetic architecture of GCA through a genome wide association study (GWAS) in a large cohort of well-characterised patients with GCA.

Methods : To demonstrate the validity of performing a large multi-centre international GWAS, we performed a pilot study, genotyping a smaller Australian cohort of GCA patients. These patients were recruited through the Arthritis Genomics Recruitment Initiative In Australasia (AGRIA). GCA was confirmed by histopathological examination of TABs with characteristic intimal infiltration with inflammatory cells and fragmentation of the internal elastic lamina. DNA was extracted from peripheral blood and genotyping was performed utilising Illumina OmniExpress SNP array. Quality control measures were applied (excluding SNPs with a call rate <0.97; a minor allele frequency (MAF) <0.05; or a Hardy–Weinberg equilibrium (HWE) < 5x10-5; and samples if they were found to be ethnic outliers or closely related).

Results : Data from a total of 162 GCA patients and a general Australian population set as controls (n=702) were analysed. Following QC a peak of association at the major histocompatibility complex (MHC) was identified. The most strongly associated SNP, rs1264326, achieving genome-wide significance (P=1.6x10-8). This SNP is located in the MHC Class I region. No other locus reached genome-wide significance, however four regions reached a suggestive level of significance.

Conclusions : Overall we provide firm evidence for genetic association with GCA. It is likely that with increasing sample sizes additional risk loci will be uncovered. Ongoing work using a large multi-centre international GCA cohort from Australasia and Europe is being undertaken.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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