Genome-wide association studies (GWAS) have identified innumerable genetic loci involved with traits and diseases. Yet –– it is usually unclear which gene (whether it be the one closest to the variant or one further away) is affected in such loci and whether the associated genetic variant(s) lead to increased or decreased gene function. In an attempt to tackle this problem, authors [attached article] have integrated the associations of common genetic variants in 57 GWAS involved in 24 studies of expression quantitative trait loci (eQTLs) from a broad range of tissues –– by using a Mendelian randomization approach.
Authors discovered a total of 3,484 examples of gene-trait-associated changes in expression –– at a false-discovery rate <0.05. These genes were often not closest to the genetic variant and were primarily identified in eQTLs derived from pathophysiologically relevant tissues. For instance, genes with expression changes that are associated with lipid traits were mostly identified in liver, whereas those associated with cardiovascular disease were identified in arterial tissue. In additin, the affected genes pointed to biological processes that had been implicated in the interrogated traits. For example, the interleukin-27 (IL27) pathway in rheumatoid arthritis. Furthermore, comparing trait-associated gene expression changes across traits suggested that pleiotropy (when a single gene produces two or more seemingly unrelated traits) is a widespread phenomenon and clearly involves specific instances of both agonistic and antagonistic pleiotropy. For instance, expression of SNX19 and ABCB9 is positively correlated with both "risk of schizophrenia" and "educational attainment". To facilitate interpretation, authors have provided this word-list of how common-trait-associated genetic variants alter gene expression in various tissues –– as the online database GWAS2Genes. Am J Hum Genet 1 June 2o17; 100: 885–894