A cross-disorder PRS-pheWAS of 5 major psychiatric disorders in UK Biobank

Psychiatric disorders are highly heritable and associated with a wide variety of social adversity and physical health problems. Using genetic liability (rather than phenotypic measures of disease) as a proxy for psychiatric disease risk can be a useful alternative for research questions that would traditionally require large cohort studies with long-term follow up. Here we conducted a hypothesis-free phenome-wide association study in about 330,000 participants from the UK Biobank to examine associations of polygenic risk scores (PRS) for five psychiatric disorders (major depression (MDD), bipolar disorder (BP), schizophrenia (SCZ), attention-deficit/ hyperactivity disorder (ADHD) and autism spectrum disorder (ASD)) with 23,004 outcomes in UK Biobank, using the open-source PHESANT software package. There was evidence after multiple testing (p<2.55x10(-06)) for associations of PRSs with 294 outcomes, most of them attributed to associations of PRS(MDD) (n = 167) and PRS(SCZ) (n = 157) with mental health factors. Among others, we found strong evidence of association of higher PRS(ADHD) with 1.1 months younger age at first sexual intercourse [95% confidence interval [CI]: -1.25,-0.92] and a history of physical maltreatment; PRS(ASD) with 0.01% lower erythrocyte distribution width [95%CI: -0.013,-0.007]; PRS(SCZ) with 0.95 lower odds of playing computer games [95%CI:0.95,0.96]; PRS(MDD) with a 0.12 points higher neuroticism score [95%CI:0.111,0.135] and PRS(BP) with 1.03 higher odds of having a university degree [95%CI:1.02,1.03]. We were able to show that genetic liabilities for five major psychiatric disorders associate with long-term aspects of adult life, including socio-demographic factors, mental and physical health. This is evident even in individuals from the general population who do not necessarily present with a psychiatric disorder diagnosis.