Polygenic risk for schizophrenia and season of birth within the UK Biobank cohort

Escott‐Price, Valentina; Smith, Daniel J.; Kendall, Kimberley; Kirov, George; Walters, James

doi:10.1017/s0033291718000454

Cited by 26 publications

(19 citation statements)

References 43 publications

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“…This suggests that confounding by such factors was not likely to explain the observed seasonal trends. Interestingly, a recent GWAS study of schizophrenia arrived at a similar conclusion in determining that any seasonality effect was likely due to a pathogenic environmental exposure [32] Second, EMD decomposes time series into IMFs which may be subjectively interpreted. We addressed this limitation by applying stringent statistical thresholds to identify only the most likely signals, thus reducing the risk of false positives.…”

Section: Discussionmentioning

confidence: 99%

Birth seasonality and risk of autism spectrum disorder

et al. 2019

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Season of birth has been hypothesized to be a risk factor for autism spectrum disorder (ASD). However, the evidence has been mixed and limited due to methodological challenges. We examine ASD birth trends for 5,464,628 births across 5 countries. ASD birth prevalence data were obtained from the International Collaboration for Autism Registry Epidemiology database, including children born in Denmark, Finland, Norway, Sweden, and Western Australia. Empirical mode decomposition and cosinor modeling were used to assess seasonality. We show seasonal variation in ASD births for the countries of Finland and Sweden. There was a modest increase in risk for children born in the fall and a modest decrease in risk for children born in the spring. Solar radiation levels around conception and the postnatal period were inversely correlated with seasonal trends in ASD risk. In the first multinational study of birth seasonality of ASD, there was evidence supporting the presence of seasonal trends in Finland and Sweden. The observations that risk was highest for fall births (i.e., conceived in the winter) and lowest for spring births (i.e., conceived in the summer), and sunlight levels during critical neurodevelopmental periods explained much of the seasonal trends, are consistent with the hypothesis that a seasonally fluctuating risk factor may influence risk of ASD. Electronic supplementary material The online version of this article (10.1007/s10654-019-00506-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Birth seasonality and risk of autism spectrum disorder

et al. 2019

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“…PRS‐SCZ was then constructed from best‐guess genotypes using PLINK at ten different p‐value thresholds (1, 0.5, 0.3, 0.2, 0.1, 0.05, 0.01, 1×10 –4 , 1×10 –6 , 5×10 –8 ). Consistent with previous research in the field, we used p=0.05 for our primary analysis, as this threshold explained most variation in the phenotype in the Psychiatric Genomics Consortium analysis.…”

Section: Methodsmentioning

confidence: 99%

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study

et al. 2019

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Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy‐genetic liability measures suggest gene‐environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS‐SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene‐environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS‐SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early‐life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS‐SCZ at 75% with alternative cut‐points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures.

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“…Within the United Kingdom biobank samples, neither SZ-PRS nor SZ-associated CNVs were associated with season or month of birth, suggesting this is not directly genetically mediated (Escott-Price et al, 2019). However, it has long been hypothesized that seasonal variation in viral exposure, particularly influenza, may underlie the associations between SZ and births early in the year.…”

Section: Season Of Birthmentioning

confidence: 96%

Environmental Risk Factors for Schizophrenia and Bipolar Disorder and Their Relationship to Genetic Risk: Current Knowledge and Future Directions

Robinson

Bergen

2021

Front. Genet.

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Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric disorders which result from complex interplay between genetic and environmental factors. It is well-established that they are highly heritable disorders, and considerable progress has been made identifying their shared and distinct genetic risk factors. However, the 15–40% of risk that is derived from environmental sources is less definitively known. Environmental factors that have been repeatedly investigated and often associated with SZ include: obstetric complications, infections, winter or spring birth, migration, urban living, childhood adversity, and cannabis use. There is evidence that childhood adversity and some types of infections are also associated with BD. Evidence for other risk factors in BD is weaker due to fewer studies and often smaller sample sizes. Relatively few environmental exposures have ever been examined for SZ or BD, and additional ones likely remain to be discovered. A complete picture of how genetic and environmental risk factors confer risk for these disorders requires an understanding of how they interact. Early gene-by-environment interaction studies for both SZ and BD often involved candidate genes and were underpowered. Larger samples with genome-wide data and polygenic risk scores now offer enhanced prospects to reveal genetic interactions with environmental exposures that contribute to risk for these disorders. Overall, although some environmental risk factors have been identified for SZ, few have been for BD, and the extent to which these account for the total risk from environmental sources remains unknown. For both disorders, interactions between genetic and environmental risk factors are also not well understood and merit further investigation. Questions remain regarding the mechanisms by which risk factors exert their effects, and the ways in which environmental factors differ by sex. Concurrent investigations of environmental and genetic risk factors in SZ and BD are needed as we work toward a more comprehensive understanding of the ways in which these disorders arise.

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Polygenic risk for schizophrenia and season of birth within the UK Biobank cohort

Abstract: Background. There is strong evidence that people born in winter and in spring have a small

Cited by 26 publications

References 43 publications

Birth seasonality and risk of autism spectrum disorder

Birth seasonality and risk of autism spectrum disorder

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study

Environmental Risk Factors for Schizophrenia and Bipolar Disorder and Their Relationship to Genetic Risk: Current Knowledge and Future Directions

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