Identification of polygenic adaptation in attention-deficit/hyperactivity disorder using gwas data
Abstract
Background During the human Diaspora out of Africa, Anatomically Modern Humans (AMH) adapted to the new environments they encountered. On top, adaptation process could have been fueled by interbreeding with homo archaic species -such as Neanderthal and Denisovan- present at that time in Eurasia. In this context of natural adaptation, Attention-Deficit/Hyperactivity Disorder (ADHD) poses an interesting evolutionary paradox: despite being associated with significant impairment, morbidity and increased rates of mortality, it is a highly prevalent phenotype. Being a highly heritable trait, several selective hypotheses have been proposed to explain the prevalence of this phenotype. In the present study, we have analysed the signatures of recent polygenic selection and the effect of archaic inbreeding in ADHD. Methods Databases: i) The effect size estimates of millions of SNPs reported at a GWAS meta-analysis on ADHD conducted by the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) and the Psychiatric Genomics Consortium (PGC) on approximately 20 K patients and 35 K controls. ii) The SDS statistic for detecting recent selection estimated in the UK10K dataset. iii) Genotypes reported at archaic European anatomically modern humans individuals (ranging from ~2 kilo years ago (kya) to ~45 kya. iv) The sequenced Altai Neanderthal genome. v) Map of Neanderthal introgression haplotypes in current humans. Analyses: The presence of signatures of recent polygenic…
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