The Phenotypic Legacy of Neanderthal Interbreeding on Modern Humans
Abstract:
Many modern human genomes retain DNA inherited from interbreeding with archaic hominins, such as Neanderthals, yet the influence of this admixture on human traits is largely unknown. We analyzed the contribution of common Neanderthal variants to over 1000 electronic health record (EHR)–derived phenotypes in ~28,000 adults of European ancestry. We discovered and replicated associations of Neanderthal alleles with neurological, psychiatric, immunological, and dermatological phenotypes. Neanderthal alleles together explained a small, but significant fraction of the variation in risk for depression and skin lesions resulting from sun exposure (actinic keratosis), and individual Neanderthal alleles were associated with specific human phenotypes, including hypercoagulation and tobacco use. Our results establish that archaic admixture influences disease risk in modern humans, provide hypotheses about the effects of hundreds of Neanderthal haplotypes, and demonstrate the utility of EHR data in evolutionary analyses.