The phenotypic legacy of admixture between modern humans and Neandertals

Corinne N Simonti; Benjamin Vernot; Lisa Bastarache; Erwin Bottinger; David S Carrell; Rex L Chisholm; David R Crosslin; Scott J Hebbring; Gail P Jarvik; Iftikhar J Kullo; Rongling Li; Jyotishman Pathak; Marylyn D Ritchie; Dan M Roden; Shefali S Verma; Gerard Tromp; Jeffrey D Prato; William S Bush; Joshua M Akey; Joshua C Denny; John A Capra

doi:10.1126/science.aad2149

The phenotypic legacy of admixture between modern humans and Neandertals

Science. 2016 Feb 12;351(6274):737-41. doi: 10.1126/science.aad2149.

Authors

Corinne N Simonti¹, Benjamin Vernot², Lisa Bastarache³, Erwin Bottinger⁴, David S Carrell⁵, Rex L Chisholm⁶, David R Crosslin⁷, Scott J Hebbring⁸, Gail P Jarvik⁷, Iftikhar J Kullo⁹, Rongling Li¹⁰, Jyotishman Pathak¹¹, Marylyn D Ritchie¹², Dan M Roden¹³, Shefali S Verma¹⁴, Gerard Tromp¹⁵, Jeffrey D Prato³, William S Bush¹⁶, Joshua M Akey², Joshua C Denny¹⁷, John A Capra¹⁸

Affiliations

¹ Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN, USA.
² Department of Genome Sciences, University of Washington, Seattle, WA, USA.
³ Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA.
⁴ Mount Sinai School of Medicine, New York, NY, USA.
⁵ Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, USA.
⁶ Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
⁷ Department of Genome Sciences, University of Washington, Seattle, WA, USA. Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, USA.
⁸ Center for Human Genetics, Marshfield Clinic, Marshfield, WI, USA.
⁹ Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
¹⁰ Division of Genomic Medicine, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
¹¹ Division of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
¹² Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA. Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA.
¹³ 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.
¹⁴ Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.
¹⁵ 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.
¹⁶ Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
¹⁷ 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.
¹⁸ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Animals
Depression / genetics
Disease / genetics*
Evolution, Molecular
Genetic Variation
Genome, Human
Haplotypes
Humans
Keratosis, Actinic / genetics
Neanderthals / genetics*
Phenotype
White People / genetics

Abstract

Publication types

MeSH terms

Grants and funding