Local adaptation in European populations affected the genetics of psychiatric disorders and behavioral traits

Renato Polimanti,Manfred H Kayser,Joel Gelernter

doi:10.1186/s13073-018-0532-7

Renato Polimanti, Manfred H Kayser + Show 1 more

Open Access

https://doi.org/10.1186/s13073-018-0532-7

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Abstract

BackgroundRecent studies have used genome-wide data to investigate evolutionary mechanisms related to behavioral phenotypes, identifying widespread signals of positive selection. Here, we conducted a genome-wide investigation to study whether the molecular mechanisms involved in these traits were affected by local adaptation.MethodsWe performed a polygenic risk score analysis in a sample of 2455 individuals from 23 European populations with respect to variables related to geo-climate diversity, pathogen diversity, and language phonological complexity. The analysis was adjusted for the genetic diversity of European populations to ensure that the differences detected would reflect differences in environmental exposures.ResultsThe top finding was related to the association between winter minimum temperature and schizophrenia. Additional significant geo-climate results were also observed with respect to bipolar disorder (sunny daylight), depressive symptoms (precipitation rate), major depressive disorder (precipitation rate), and subjective well-being (relative humidity). Beyond geo-climate variables, we also observed findings related to pathogen diversity and language phonological complexity: openness to experience was associated with protozoan diversity; conscientiousness and extraversion were associated with language consonants.ConclusionsWe report that common variation associated with psychiatric disorders and behavioral traits was affected by processes related to local adaptation in European populations.

Highlights

Recent studies have used genome-wide data to investigate evolutionary mechanisms related to behavioral phenotypes, identifying widespread signals of positive selection
To investigate whether molecular mechanisms at the basis of psychiatric/ behavioral traits (Table 1) were affected by local-adaptation processes that occurred during the colonization of Europe [14], we conducted a Polygenic risk score (PRS) analysis based on Genome-wide association study (GWAS) of psychiatric disorders and behavioral traits (Table 1) from the Psychiatric Genomics Consortium [15,16,17], the Genetics of Personality Consortium [18,19,20], and the Social Science Genetic Association Consortium [21] in a sample of 2455 individuals from 23 European populations
This approach was considered on the basis of the experience of many GWAS and PRS analyses conducted on samples containing populations of different European descents

Summary

Introduction

Recent studies have used genome-wide data to investigate evolutionary mechanisms related to behavioral phenotypes, identifying widespread signals of positive selection (i.e., variants with beneficial effects on individual fitness increase in population frequency) in the predisposition to psychiatric disorder and behavioral traits [1,2,3]. Brainrelated phenotypes have undergone polygenic adaptation (adaptation that occurs by simultaneous selection on variants at many loci) during different phases of human evolutionary history [4] including to the present day [5] This is consistent with several other investigations that found evidence of polygenic adaptation for predisposition to Polimanti et al Genome Medicine (2018) 10:24 of European descent generate biased results when applied to non-European samples [13]. We conducted a Gene Ontology (GO) enrichment analysis based on PRS results to provide information regarding the specific molecular mechanisms involved in the polygenic signatures of local adaptation observed

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