Performance of gout definitions for genetic epidemiological studies: analysis of UK Biobank

Murray Cadzow, Tony R. Merriman, Nicola Dalbeth

Many different combinations of available data have been used to identify gout cases in large genetic studies. The aim of this study was to determine the performance of case definitions of gout using the limited items available in multipurpose cohorts for population-based genetic studies. This research was conducted using the UK Biobank Resource. Data, including genome-wide genotypes, were available for 105,421 European participants aged 40-69 years without kidney disease. Gout definitions and combinations of these definitions were identified from previous epidemiological studies. These definitions were tested for association with 30 urate-associated single-nucleotide polymorphisms (SNPs) by logistic regression, adjusted for age, sex, waist circumference, and ratio of waist circumference to height. Heritability estimates under an additive model were generated using GCTA version 1.26.0 and PLINK version 1.90b3.32 by partitioning the genome. There were 2066 (1.96%) cases defined by self-report of gout, 1652 (1.57%) defined by urate-lowering therapy (ULT) use, 382 (0.36%) defined by hospital diagnosis, 1861 (1.76%) defined by hospital diagnosis or gout-specific medications and 2295 (2.18%) defined by self-report of gout or ULT use. Association with gout at experiment-wide significance (P < 0.0017) was observed for 13 SNPs with gout using the self-report of gout or ULT use definition, 12 SNPs using the self-report of gout definition, 11 SNPs using the hospital diagnosis or gout-specific medication definition, 10 SNPs using ULT use definition and 3 SNPs using hospital diagnosis definition. Heritability estimates ranged from 0.282 to 0.308 for all definitions except hospital diagnosis (0.236). Of the limited items available in multipurpose cohorts, the case definition of self-report of gout or ULT use has high sensitivity and precision for detecting association in genetic epidemiological studies of gout.