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.
authors.affiliation: Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.
authors.forename: Corinne N
authors.initials: CN
authors.lastname: Simonti
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Vernot
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bastarache
authors.affiliation: Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Erwin
authors.initials: E
authors.lastname: Bottinger
authors.affiliation: Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Carrell
authors.affiliation: Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Rex L
authors.initials: RL
authors.lastname: Chisholm
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA. Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Crosslin
authors.affiliation: Center for Human Genetics, Marshfield Clinic, Marshfield, WI, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hebbring
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA. Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
authors.affiliation: Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Rongling
authors.initials: R
authors.lastname: Li
authors.affiliation: Division of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Jyotishman
authors.initials: J
authors.lastname: Pathak
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA. Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.affiliation: Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA. Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA. Department of Medicine, Vanderbilt University, Nashville, TN, USA. Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Shefali S
authors.initials: SS
authors.lastname: Verma
authors.affiliation: Weis Center for Research, Geisinger Health System, Danville, PA, USA. Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Health Science, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Prato
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Bush
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Akey
authors.affiliation: Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA. Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA. Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA. Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA. Department of Biological Sciences, Vanderbilt University, Nashville, TN, USA. Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Capra
mesh_terms: D000483:Alleles; D000818:Animals; D003863:Depression / Q000235:genetics; D004194:Disease / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D055623:Keratosis, Actinic / Q000235:genetics; D059125:Neanderthals / Q000235:genetics*; D010641:Phenotype; D044465:White People / Q000235:genetics