Mendelian pathway analysis of laboratory traits reveals distinct roles for ciliary subcompartments in common disease pathogenesis (2023) Theodore George Drivas

Description

Rare monogenic disorders of the primary cilium (ciliopathies) are characterized by extreme presentations of common diseases, such as diabetes, hepatic fibrosis, and kidney failure. This study investigates the contribution of common genetic variants within Mendelian ciliopathy genes to common complex diseases pathogenesis. Researchers performed association studies of 16,874 common genetic variants across 122 ciliary genes with 12 quantitative laboratory traits in 452,593 individuals in the UK Biobank, identifying 101 statistically significant associations. The findings challenge the widely held belief that the cilium is an organelle important mainly in rare syndromic disease pathogenesis, demonstrating the utility of a Mendelian pathway-based approach to genomic association studies.