Abstract
BackgroundMany 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.MethodsThis 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.ResultsThere 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-reportof 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).ConclusionsOf 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.
Highlights
Many different combinations of available data have been used to identify gout cases in large genetic studies
In multipurpose cohort studies frequently used for genetic epidemiological studies of gout, limited information is usually available for case definition
The aim of the present study was to determine the performance of case definitions of gout using the limited items available in multipurpose cohorts, including self-report of gout or urate-lowering therapy (ULT) use, for population-based genetic studies
Summary
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. Accurate case definition is important for epidemiological studies. In multipurpose cohort studies frequently used for genetic epidemiological studies of gout, limited information is usually available for case definition. Population genetic studies frequently require large numbers of participants to achieve adequate statistical power, because common variants typically exert small effects on risk of disease. Consistent case definition is important for analyses that pool genetic data from different studies, as well as for those analyses that aim to replicate reported genetic associations
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