found that genomic regions tagged by negative NSS scores show enrichment of association with schizophrenia. Negative NSS scores can be used to pinpoint mutations (usually single nucleotide changes) that were positively selected in humans as they diverged from Neanderthals. Comparison of Neanderthal and human genome sequences has revealed genomic regions that have experienced a selective sweep in modern humans, presumably following a favorable mutation. Neanderthals were hominids that co-existed and even bred with modern humans. showed that genes near HARs are enriched for association with schizophrenia. HARs are genomic regions that are highly conserved in non-human species, but have undergone rapid sequence change in the human lineage. This field has introduced new datasets to test disease origins in humans, including Human Accelerated Regions (HARs) and Neanderthal Selective Sweep (NSS) scores. One approach to investigating the function of schizophrenia-associated variants is comparative genomics, which investigates the evolutionary relevance of certain genomic regions. Large genome-wide association studies (GWAS) have identified thousands of variants that are associated with schizophrenia but our mechanistic understanding of the candidate variants is poor. This evolutionary hypothesis of the origins of schizophrenia can now be tested, thanks to the identification of genetic factors implicated in schizophrenia and the availability of datasets that reflect recent genomic evolution in humans.

Crow first argued that language and psychosis may have common origins, which could explain the persistence of schizophrenia in human populations. One explanation for this persistence is that evolution has indirectly selected the disease instead of eliminating it - the disease may co-segregate with creativity and intellectual prowess, providing selective advantages to the kin of affected individuals. They henceforth suggested hitherto unknown mechanisms for persistence of the disease. leveraged Swedish registry data to demonstrate the reduced fecundity of patients with schizophrenia, despite the novel finding that sisters of individuals with schizophrenia had higher fitness than controls. It is associated with reduced fertility and increased mortality, and its persistence despite this heavy burden is paradoxical. Today, schizophrenia is estimated to have a prevalence of 1%. Family, twin and adoption studies estimate that schizophrenia has a high heritability of 60вЂ“90%. Schizophrenia is a psychiatric disorder that has been reported throughout human history, possibly as far back as 5000В years. Since methylation is an epigenetic mark, potentially mediated by environmental changes, our results also suggest that interaction with the environment might have contributed to that association.

Our study further supports the hypothesis that genetic variants conferring risk of schizophrenia co-occur in genomic regions that have changed as the human species evolved. Regions where DNA methylation modifications have changed during recent human evolution show enrichment of association with schizophrenia and possibly with height. Some enrichment of association with height was observed at the gene level. The enrichment survives multiple testing performed through permutation ( nвЂ‰=вЂ‰10,000) and bootstrapping ( nвЂ‰=вЂ‰5000) in INRICH ( pвЂ‰<вЂ‰0.01). The enrichment seen in human DMRs is comparable to that for genomic regions tagged by Neanderthal Selective Sweep markers, and stronger than that for Human Accelerated Regions.

The enrichment was not observed for Neanderthal or Denisovan DMRs. Schizophrenia was the only trait in which DMR SNPs showed clear enrichment of association that passed the genome-wide significance threshold. We used analytical tools that evaluate polygenic enrichment of a subset of genomic variants against all variants. human-specific differentially methylated regions (DMRs). Using summary statistics from genome-wide association studies (GWAS) of schizophrenia and 11 other phenotypes, we tested for enrichment of association with GWAS traits in regions that have undergone methylation changes in the human lineage compared to Neanderthals and Denisovans, i.e. This hypothesis is supported by evidence suggesting that recently-evolved genomic regions in humans are involved in the genetic risk for schizophrenia.

One explanation for the persistence of schizophrenia despite the reduced fertility of patients is that it is a by-product of recent human evolution.

Human evolution project magenta