Linking protein to phenotype with Mendelian Randomization detects 38 proteins with causal roles in human diseases and traits.

ABSTRACT: To efficiently transform genetic associations into drug targets requires evidence that a particular gene, and its encoded protein, contribute causally to a disease. To achieve this, we employ a three-step proteome-by-phenome Mendelian Randomization (MR) approach. In step one, 154 protein quantitative trait loci (pQTLs) were identified and independently replicated. From these pQTLs, 64 replicated locally-acting variants were used as instrumental variables for proteome-by-phenome MR across 846 traits (step two). When its assumptions are met, proteome-by-phenome MR, is equivalent to simultaneously running many randomized controlled trials. Step 2 yielded 38 proteins that significantly predicted variation in traits and diseases in 509 instances. Step 3 revealed that amongst the 271 instances f

SUBMITTER: Bretherick AD 

PROVIDER: S-EPMC7337286 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature