A cross-disorder PRS-pheWAS of 5 major psychiatric disorders in UK Biobank
Autoři:
Beate Leppert aff001; Louise A. C. Millard aff001; Lucy Riglin aff004; George Davey Smith aff001; Anita Thapar aff004; Kate Tilling aff001; Esther Walton aff001; Evie Stergiakouli aff001
Působiště autorů:
MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, United Kingdom
aff001; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
aff002; Intelligent Systems Laboratory, University of Bristol, Bristol, United Kingdom
aff003; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom
aff004; Division of Psychological Medicine and Clinical Neurosciences; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom
aff004; Department of Psychology, University of Bath, Bath, United Kingdom
aff005
Vyšlo v časopise:
A cross-disorder PRS-pheWAS of 5 major psychiatric disorders in UK Biobank. PLoS Genet 16(5): e32767. doi:10.1371/journal.pgen.1008185
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008185
Souhrn
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 PRSMDD (n = 167) and PRSSCZ (n = 157) with mental health factors. Among others, we found strong evidence of association of higher PRSADHD with 1.1 months younger age at first sexual intercourse [95% confidence interval [CI]: -1.25,-0.92] and a history of physical maltreatment; PRSASD with 0.01% lower erythrocyte distribution width [95%CI: -0.013,-0.007]; PRSSCZ with 0.95 lower odds of playing computer games [95%CI:0.95,0.96]; PRSMDD with a 0.12 points higher neuroticism score [95%CI:0.111,0.135] and PRSBP 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.
Klíčová slova:
ADHD – Autism spectrum disorder – Bipolar disorder – Clinical genetics – Depression – Genome-wide association studies – Mental health and psychiatry – Schizophrenia
Zdroje
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