Detection and interpretation of shared genetic influences on 42 human traits

Joseph Pickrell and colleagues analyze genome-wide association data for 42 human phenotypes or diseases and identify several hundred loci influencing multiple traits. They also find several traits with overlapping genetic architectures as well as pairs of traits showing evidence of a causal relationship. We performed a scan for genetic variants associated with multiple phenotypes by comparing large genome-wide association studies (GWAS) of 42 traits or diseases. We identified 341 loci (at a false discovery rate of 10%) associated with multiple traits. Several loci are associated with multiple phenotypes; for example, a nonsynonymous variant in the zinc transporter SLC39A8 influences seven of the traits, including risk of schizophrenia (rs13107325: log-transformed odds ratio (log OR) = 0.15, P = 2 × 10−12) and Parkinson disease (log OR = −0.15, P = 1.6 × 10−7), among others. Second, we used these loci to identify traits that have multiple genetic causes in common. For example, variants associated with increased risk of schizophrenia also tended to be associated with increased risk of inflammatory bowel disease. Finally, we developed a method to identify pairs of traits that show evidence of a causal relationship. For example, we show evidence that increased body mass index causally increases triglyceride levels.