Elisabeth De Smit1 ,2, Linda Clarke1 ,2, Lisa Kearns1 ,2, Catherine Hill3, Penny McKelvie8, Jamie Craig9, Celia Chen9, Svetlana Cherepanoff10, Members of the Australian Giant Cell Arteritis Genetic7, David A. Mackey6, Erika de Guzman4, Katie Cremin4, Paul Leo4, David Evans4, Matt A. Brown4, Alex W. Hewitt1 ,5

Purpose: Giant Cell Arteritis (GCA) is the most common systemic inflammatory vasculitis affecting people aged over 50 years. It is one of the few true ophthalmic emergencies. To date little is known about the patho-aetiology of GCA. Genetic studies have been limited in view of the challenges associated with recruiting adequately large numbers of patients.

The goal of our research is to investigate the genetic architecture of GCA. We hypothesise that common genetic variants contribute significantly to the genetic susceptibility for GCA. As such we are conducting an international genome wide association study (GWAS) in a large cohort of well-characterised patients with GCA (aim of 2,000 GCA cases).

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. GCA was defined histopathologically. DNA was extracted from blood. Genotyping was performed utilising Illumina OmniExpress SNP array. Quality control measures were applied (excluding SNPs with a call rate <0.97).

Results: Our pilot data, which included GCA patients (n=162) and controls (n=702), showed a peak of association at the major histocompatibility complex (MHC) with the most strongly associated SNP, rs1264326, achieving genome-wide significance (P=1.6×10^-8). This SNP is located in the MHC Class I region.

Conclusion: Results of this pilot dataset provide evidence for genetic association and support to conduct a large multi-centre international GCA case-control GWAS. Our international GWAS collaboration is now well established and to date we have 2300 GCA samples recruited from both Australasia and Europe.