Phenotype-Specific Enrichment of Mendelian Disorder Genes near GWAS Regions across 62 Complex Traits

Although recent studies provide evidence for a common genetic basis between complex traits and Mendelian disorders, a thorough quantification of their overlap in a phenotype-specific manner remains elusive. Here, we have quantified the overlap of genes identified through large-scale genome-wide association studies (GWASs) for 62 complex traits and diseases with genes containing mutations known to cause 20 broad categories of Mendelian disorders. We identified a significant enrichment of genes linked to phenotypically matched Mendelian disorders in GWAS gene sets; of the total 1,240 comparisons, a higher proportion of phenotypically matched or related pairs (n = 50 of 92 [54%]) than phenotypically unmatched pairs (n = 27 of 1,148 [2%]) demonstrated significant overlap, confirming a phenotype-specific enrichment pattern.

Source: The American Journal of Human Genetics - October 4, 2018 Category: Genetics & Stem Cells Authors: Malika Kumar Freund, Kathryn S. Burch, Huwenbo Shi, Nicholas Mancuso, Gleb Kichaev, Kristina M. Garske, David Z. Pan, Zong Miao, Karen L. Mohlke, Markku Laakso, P äivi Pajukanta, Bogdan Pasaniuc, Valerie A. Arboleda Tags: Article Source Type: research