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Background: Genome-wide scans have revealed that Darwinian natural selection affects human genome during human evolution, helping us to optimize complex human adaptations. Natural selection is also reflected in significant associations with human phenotypes, e.g., single genomic locus associated with diverse complex disorders and traits. Method: Meta-analyses of single nucleotide polymorphisms (SNPs) in 10q24.33 with schizophrenia in Asian populations were conducted. Population genetic analyses of the schizophrenia risk SNPs were also conducted in diverse populations. Results: We report a SNP rs11191580 in 10q24.33 to be significantlyassociated with schizophrenia in Asians. Further pleiotropic analyses reveal that the schizophrenia non-risk allele [C] at rs11191580 also reduces risk of blood pressure and hypertension in both European and Asian populations. The non-risk allele [C] is present in populations from Europe and Asia mainland, but totally absent in Africans. Further evolutionary analyses show that the derived allele (i.e., C-allele) has experienced recent positive selection in Europeans and Asians. Through subsequent exploratory analysis, we propose that the colder environment in Europe and Asia is likely the selection pressure, i.e., when modern humans migrated “out of Africa” and moved to Europe and Asia mainland (the continent colder than Africa), new allele derived due to positive selection. This new allele probably helped human beings to adapt to the cold environment and also protected them from risk of hypertension. Conclusion: The current data provides an intriguing example demonstrating the reflection of natural selection on pleiotropic genomic locus, illustrating a possible mechanism of selection pressures in human populations.

journal of psychiatry and brain science

Recent Positive Selection Drives the Expansion of a Schizophrenia-associated Variant within 10q24.33 in Human Populations through Its Pleiotropic Effects on Diverse Human Complex Traits