Season of birth and subclinical psychosis: systematic review and meta-analysis of new and existing data

Season of birth (SOB) has been shown to modify the risk of several health outcomes, including a number of neuropsychiatric disorders. Empirical evidence indicates that subclinical forms of psychosis in the general population share some risk factors with categorical diagnoses of psychosis. Hence, by systematically reviewing and meta-analyzing new and existing data, the current work aimed to determine whether there is evidence of an association between winter SOB and subclinical psychosis in the general population. Our meta-analytic results do not indicate an association between winter SOB and schizotypy in adult populations, although they indicate winter SOB may be a risk factor for psychotic experiences or symptoms in children around 12-15 years (OR=1.12, 95%CI:1.03-1.21). In the whole new dataset for adults (n=481, mean age=22.8 years) no association was detected in either an unadjusted model or adjusting for gender and age. Overall, our results indicate that the association between winter SOB and increased subclinical psychosis may hold in children, but does not in the broad general adult population. Nevertheless, the epidemiological and clinicopathological significance of winter SOB as a risk factor for subclinical psychosis would probably be slight due to the small effect sizes indicated by the reports available to date

Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations

Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes(1). This recent study-and most other large-scale human genetics studies-was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 x 10(-6)). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.Peer reviewe