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

English version

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 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.

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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