| Title: | M91 POLYGENIC RISK FOR SCHIZOPHRENIA AND SEASON OF BIRTH WITHIN THE UK BIOBANK COHORT |
| Journal: | European Neuropsychopharmacology |
| Published: | 1 Jan 2019 |
| DOI: | https://doi.org/10.1016/j.euroneuro.2017.08.398 |
| URL: | https://eprints.gla.ac.uk/156580/7/156580.pdf |
Publication 8195
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Abstract
Background People born in winter and early spring are at an elevated risk for schizophrenia [1-4]. Although the effect is small, with an increase in risk of about around 10%, this season of birth effect is one of the most robust findings in schizophrenia epidemiology [5]. It has also been influential in developing hypotheses of schizophrenia pathogenesis, forming one of the central planks of the viral infection hypothesis of the disorder [6] as well as other less intensively investigated putative mechanisms including vitamin D deficiency during fetal development [7]. However, at present, the mechanisms underpinning this season of birth effect are unknown. Methods We implement PRS analysis of the UK Biobank (UKBB) to determine whether season of birth is associated with genetic risk for schizophrenia. We generated schizophrenia PRS for every participant in the UKBB (June 2015 release, N=136,538) and tested whether this score is associated with month or season of birth. As a secondary test of the plausibility of season of birth being a genetically correlated confound, we also conducted a GWAS of season of birth as a binary phenotype, comparing winter/spring births with summer/autumn. Our aim was to estimate heritability of season of birth as a phenotype. Results We found no association between schizophrenia PRS and season of birth in the UK Biobank sample and no differences in schizophrenia risk scores with respect to month of birth. No SNPs were associated with season of birth at genome-wide significance, there was no evidence for inflation in the test statistics indicative of polygenic inheritance and no evidence that SNP heritability contributed to this trait (total liability scale h2=-0.002 SE=0.0052 as estimated by LD-Score regression). Discussion In this study, we examined seasonality in regard to genetic risk to schizophrenia within UK Biobank. We used the largest schizophrenia dataset to date for identification of genetic risk loci and one of the largest available population cohorts to generate schizophrenia PRS and test for seasonal differences in genetic liability to schizophrenia. We found no trends of elevated schizophrenia polygenic risk scores in people born in winter or spring. These results were further supported by a lack of evidence that seasonality is a heritable trait. Since the PRS analysis and heritability estimates were based upon common SNPs, we don't exclude a possible role for rare SNPs, however the frequencies of rare CNVs, linked to neurodevelopmental disorders, also did not differ by season of birth.8 Authors
- Valentina Escott-Price
- Daniel Smith
- Kimberley Kendall
- Joey Ward
- George Kirov
- Michael Owen
- James Walters
- Michael O'Donovan
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