PT  - JOURNAL ARTICLE
AU  - Niladri Banerjee
AU  - Tatiana Polushina
AU  - Francesco Bettella
AU  - Sudheer Giddaluru
AU  - Vidar M. Steen
AU  - Ole A. Andreassen
AU  - Stephanie Le Hellard
TI  - Human-specific methylated regions are enriched in schizophrenia
AID  - 10.1101/113175
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 113175
4099  - http://biorxiv.org/content/early/2017/03/02/113175.short
4100  - http://biorxiv.org/content/early/2017/03/02/113175.full
AB  - Background Despite the reduced fertility of patients, schizophrenia has a prevalence of ~1% in the general population. One explanation for this persistence is that schizophrenia is a by-product of human evolution. This hypothesis is supported by evidence suggesting that recently-evolved genomic regions in humans are involved in the genetic risk for schizophrenia. We tested if genetic variants located within human-specific differentially methylated regions (DMRs) are enriched for association with schizophrenia.Methods We used analytical tools that evaluate the polygenic enrichment of a set of genomic variants against all genomic variants. SNPs identified in genome-wide association studies (GWAS) of schizophrenia and 11 other phenotypes were classified according to their location in previously defined human-specific DMRs. These DMR SNPs were then tested for enrichment of association with the GWAS trait.Results Schizophrenia was the only trait in which GWAS SNPs within human-specific DMRs showed clear enrichment of association that passed the genome-wide significance threshold. The enrichment was not observed for Neanderthal or Denisovan DMRs. 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.Conclusions Regions where DNA methylation modifications have changed during recent human evolution harbor more schizophrenia-associated genetic variants than expected. 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. Our results also suggest that interaction with the environment might have contributed to that association.