To evaluate medical outcomes associated with EXT, we conducted a phenome-wide association study (PheWAS) in 66,915 genotyped individuals of European-ancestry in the BioVU biorepository, a U.S.-based biobank of electronic health records from the Vanderbilt University Medical Center46. A logistic regression was fit to 1,335 case/control disease phenotypes. 255 disease phenotypes were associated with the EXT polygenic score at false discovery rate <0.05, with odds ratios ranging from 0.8 to 1.4 per standard deviation increase in the score (Figure 4 and Supplementary Table 32). The most abundant associations were with mental and behavioral disorders, such as substance use, mood disorders, suicidal ideation, and attempted suicide. Individuals with higher EXT polygenic scores also showed worse health in nearly every bodily system. They were more likely to suffer, for example, from ischemic heart disease, viral hepatitis C and HIV infection, type 2 diabetes and obesity, cirrhosis of liver, sepsis, and lung cancer. Behaviors related to self-regulation, e.g., smoking, drinking, drug use, condomless sex, and overeating, contribute to many of these medical outcomes.
