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 300,000 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<2.55×10−06) for associations of PRSs with 226 outcomes, most of them attributed to associations of PRSMDD (n=120) with mental health factors and PRSADHD (n=77) with socio-demographic factors. Among others, we found strong evidence of associations between a 1 standard deviation increase in PRSADHD with 1.1 months younger age at first sexual intercourse [95% confidence interval [CI]: −1.26,−0.94]; PRSASD with 0.01% reduced lower erythrocyte distribution width [95%CI: −0.013,-0.007]; PRSSCZ with 0.98 odds of playing computer games [95%CI:0.976,0.989]; PRSMDD with a 0.11 points higher neuroticism score [95%CI:0.094,0.118] and PRSBP with 1.04 higher odds of having a university degree [95%CI:1.033,1.048]. 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