Moreover, schizophrenia has been associated with high rates of comorbid illnesses such as coronary heart disease, stroke, diabetes, respiratory diseases 5, 7 and a 15% rate of unnatural deaths, including suicide 5.įamily, twin, and adoption studies have estimated schizophrenia heritability to be 65–80% 8, thus corroborating the major contribution of genetic variability to the development of the disorder. ![]() Affecting around 0.5% of the human population 4, schizophrenia is associated with increased mortality 5 and a low rate of recovery of only 13.5% 6. Although the typical onset does not occur until adolescence or early adulthood, epidemiological and molecular evidence has consistently described the early neurodevelopmental nature of the disorder 1, 2, 3. delusions or hallucinations), social and emotional withdrawal, and cognitive deficits. Schizophrenia is a complex mental disorder characterized by psychosis (i.e. Taken together, our results suggest non-antagonistic pleiotropy as a likely mechanism behind RNS that could explain the persistence of schizophrenia common predisposing variation in human populations due to its association to other non-psychiatric phenotypes. Moreover, both partitioned heritability and gene set enrichment analyses of mapped genes from schizophrenia predisposing loci subject to RNS revealed a lower involvement in brain and neuronal related functions compared to those not subject to RNS. We found evidence for significant enrichment of RNS markers in derived alleles arisen during human evolution conferring protection to schizophrenia. Here in this study, we used 1000 Genomes Project data to explore the relationship between schizophrenia predisposing loci and recent natural selection (RNS) signatures after the human diaspora out of Africa around 100,000 years ago on a genome-wide scale. Furthermore, evolutionary pressures on schizophrenia risk alleles could have changed throughout human history as new environments emerged. ![]() However, recent studies have shown strong evidence against a positive selection of predisposing loci. ![]() Previous research has suggested balanced selection, a mechanism by which schizophrenia risk alleles could also provide advantages under certain environments, as a reliable explanation. Schizophrenia is a debilitating psychiatric disorder associated with a reduced fertility and decreased life expectancy, yet common predisposing variation substantially contributes to the onset of the disorder, which poses an evolutionary paradox.
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