Large-scale genome-wide enrichment analyses identify new trait-associated genes and pathways across 31 human phenotypes

• DOI: 10.1038/s41467-018-06805-x
• Publication Date: 2018-10-15T13:53:31Z
• Authors: Xiang Zhu; Matthew Stephens
• Keywords: Genome-wide Association Study; Trait; Biological pathway

Abstract Genome-wide association studies (GWAS) aim to identify genetic factors associated with phenotypes. Standard analyses test variants for associations individually. However, variant-level are hard and can be difficult interpret biologically. Enrichment help address both problems by targeting sets of biologically related variants. Here we introduce a new model-based enrichment method that requires only GWAS summary statistics. Applying this interrogate 4,026 gene in 31 human phenotypes identifies many previously-unreported enrichments, including enrichments endochondral ossification pathway height, NFAT-dependent transcription rheumatoid arthritis, brain-related genes coronary artery disease, liver-related Alzheimer’s disease. A key feature our is inferred automatically trait-associated genes. For example, accounting lipid transport highlights between MTTP low-density lipoprotein levels, whereas conventional the same data found no significant near gene.