@article{8cde41487d714f0bbd8e9562d85a4c9b,
title = "The phenotypic legacy of admixture between modern humans and Neandertals",
abstract = "Many modern human genomes retain DNA inherited from interbreeding with archaic hominins, such as Neandertals, yet the influence of this admixture on human traits is largely unknown. We analyzed the contribution of common Neandertal variants to over 1000 electronic health record (EHR) - derived phenotypes in ∼28,000 adults of European ancestry. We discovered and replicated associations of Neandertal alleles with neurological, psychiatric, immunological, and dermatological phenotypes. Neandertal alleles together explained a significant fraction of the variation in risk for depression and skin lesions resulting from sun exposure (actinic keratosis), and individual Neandertal alleles were significantly 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 Neandertal haplotypes, and demonstrate the utility of EHR data in evolutionary analyses.",
author = "Simonti, {Corinne N.} and Benjamin Vernot and Lisa Bastarache and Erwin Bottinger and Carrell, {David S.} and Chisholm, {Rex L.} and Crosslin, {David R.} and Hebbring, {Scott J.} and Jarvik, {Gail P.} and Kullo, {Iftikhar J.} and Rongling Li and Jyotishman Pathak and Ritchie, {Marylyn D.} and Roden, {Dan M.} and Verma, {Shefali S.} and Gerard Tromp and Prato, {Jeffrey D.} and Bush, {William S.} and Akey, {Joshua M.} and Denny, {Joshua C.} and Capra, {John A.}",
note = "Funding Information: The data reported in this paper are available in the supplementary materials and in the Neandertal PheWAS Catalog (https://phewas.mc.vanderbilt.edu/neanderthal). The raw genotype and phenotype data used in this study are subject to the data use and availability requirements of the eMERGE network outlined at https://emerge.mc.vanderbilt. edu/collaborate. We thank A. Fish, J. Hall, D. Mortlock, D. Samuels, M. Sivley, and P. Wu for helpful discussions. C.N.S. was supported by NIH grant 5T32EY021453 to Vanderbilt University and a pilot project award from the Vanderbilt Center for Quantitative Sciences. The Emerge Network was initiated and funded by the National Human Genome Research Institute through the following grants: U01HG004438 to Johns Hopkins University; U01HG004610 and U01HG008657 to Group Health Cooperative and University of Washington, Seattle; U01HG004608 and 1K22LM011938 to the Marshfield Clinic; U01HG006389 to the Essentia Institute of Rural Health; U01HG04599 and U01HG006379 to the Mayo Clinic; U01HG004609 and U01HG006388 to Northwestern University; U01HG04603 and U01HG006378 to Vanderbilt University; U01HG006385 to the Coordinating Center of the eMERGE Network; U01HG006382 to the Geisinger Clinic; and U01HG006380 to the Mount Sinai School of Medicine. J.M.A. is a paid consultant for Glenview Capital and provides advice on next-generation sequencing technologies. PheWAS method development was supported by grant R01LM010685. J.M.A. was supported in part by NIH grant R01GM110068. S.J.H was supported in part by NIH grant 1R01GM114128. The authors report no conflicts of interest. Publisher Copyright: {\textcopyright} 2016, American Association for the Advancement of Science. All rights reserved.",
year = "2016",
month = feb,
day = "12",
doi = "10.1126/science.aad2149",
language = "English (US)",
volume = "351",
pages = "737--741",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6274",
}