Epidemiology of polymyalgia rheumatica and giant cell arteritis

Polymyalgia rheumatica and giant cell arteritis are two inflammatory disorders that are more common among female individuals with Scandinavian ancestry. The conditions co-occur in the same individual more often than expected by chance, share common symptoms and are difficult to diagnose. Earlier genetic studies identified a genetic association for both diseases with the HLA-DRB1*04 allele. Non-genetic data from UK Biobank were used in order to explore association with factors related to the susceptibility and severity of these diseases. Additionally, genetic data from UK GCA consortium were used in order to explore for potential genetic differences among clinically diagnosed GCA cases with different results from temporal artery biopsy (TAB), a gold standard method of diagnosis. Finally, genetic data from UK Biobank were used for the genome-wide association study of PMR cases. The results from the genetic analysis of PMR and GCA cases were further analysed for the identification of potential cross-phenotype associations. Cases with PMR and GCA were more likely to report a previous diagnosis of hypothyroidism, transient ischaemic attack and hypertension. Female cases with PMR were more likely to have ever received hormone replacement treatment and female cases with GCA to have an early menopause (<43 years). GCA cases were found to have a strong association with HLA-DRB1*0401 and PMR cases with HLA-DRB1*0404. The estimated proportion of patients misdiagnosed as GCA was 67% in the negative-TAB group and 33% in the group without TAB result. Meta-analysis results reveal a novel association with rs148462291 in chromosome 3. Pair-wise analysis of PMR and GCA data suggest this variant is associated with both PMR and GCA. There was no evidence that shared genetic risk factors were due to subgroup heterogeneity within PMR cases, although this analysis lacked statistical power.