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Directional dominance on stature and cognition in diverse human populations.

About this Publication
Title
Directional dominance on stature and cognition in diverse human populations.
Pubmed ID
26131930 (View this publication on the PubMed website)
Publication
Nature. 2015 Jul; Volume 523 (Issue 7561): Pages 459-462
Authors
Joshi PK, Esko T, Mattsson H, Eklund N, Gandin I, Nutile T, Jackson AU, Schurmann C, Smith AV, Zhang W, Okada Y, Stančáková A, Faul JD, Zhao W, Bartz TM, Concas MP, Franceschini N, Enroth S, Vitart V, Trompet S, ...show more Guo X, Chasman DI, O'Connel JR, Corre T, Nongmaithem SS, Chen Y, Mangino M, Ruggiero D, Traglia M, Farmaki AE, Kacprowski T, Bjonnes A, van der Spek A, Wu Y, Giri AK, Yanek LR, Wang L, Hofer E, Rietveld CA, McLeod O, Cornelis MC, Pattaro C, Verweij N, Baumbach C, Abdellaoui A, Warren HR, Vuckovic D, Mei H, Bouchard C, Perry JRB, Cappellani S, Mirza SS, Benton MC, Broeckel U, Medland SE, Lind PA, Malerba G, Drong A, Yengo L, Bielak LF, Zhi D, van der Most PJ, Shriner D, Mägi R, Hemani G, Karaderi T, Wang Z, Liu T, Demuth I, Zhao JH, Meng W, Lataniotis L, van der Laan SW, Bradfield JP, Wood AR, Bonnefond A, Ahluwalia TS, Hall LM, Salvi E, Yazar S, Carstensen L, de Haan HG, Abney M, Afzal U, Allison MA, Amin N, Asselbergs FW, Bakker SJL, Barr RG, Baumeister SE, Benjamin DJ, Bergmann S, Boerwinkle E, Bottinger EP, Campbell A, Chakravarti A, Chan Y, Chanock SJ, Chen C, Chen YI, Collins FS, Connell J, Correa A, Cupples LA, Smith GD, Davies G, Dörr M, Ehret G, Ellis SB, Feenstra B, Feitosa MF, Ford I, Fox CS, Frayling TM, Friedrich N, Geller F, Scotland G, Gillham-Nasenya I, Gottesman O, Graff M, Grodstein F, Gu C, Haley C, Hammond CJ, Harris SE, Harris TB, Hastie ND, Heard-Costa NL, Heikkilä K, Hocking LJ, Homuth G, Hottenga JJ, Huang J, Huffman JE, Hysi PG, Ikram MA, Ingelsson E, Joensuu A, Johansson Å, Jousilahti P, Jukema JW, Kähönen M, Kamatani Y, Kanoni S, Kerr SM, Khan NM, Koellinger P, Koistinen HA, Kooner MK, Kubo M, Kuusisto J, Lahti J, Launer LJ, Lea RA, Lehne B, Lehtimäki T, Liewald DCM, Lind L, Loh M, Lokki ML, London SJ, Loomis SJ, Loukola A, Lu Y, Lumley T, Lundqvist A, Männistö S, Marques-Vidal P, Masciullo C, Matchan A, Mathias RA, Matsuda K, Meigs JB, Meisinger C, Meitinger T, Menni C, Mentch FD, Mihailov E, Milani L, Montasser ME, Montgomery GW, Morrison A, Myers RH, Nadukuru R, Navarro P, Nelis M, Nieminen MS, Nolte IM, O'Connor GT, Ogunniyi A, Padmanabhan S, Palmas WR, Pankow JS, Patarcic I, Pavani F, Peyser PA, Pietilainen K, Poulter N, Prokopenko I, Ralhan S, Redmond P, Rich SS, Rissanen H, Robino A, Rose LM, Rose R, Sala C, Salako B, Salomaa V, Sarin AP, Saxena R, Schmidt H, Scott LJ, Scott WR, Sennblad B, Seshadri S, Sever P, Shrestha S, Smith BH, Smith JA, Soranzo N, Sotoodehnia N, Southam L, Stanton AV, Stathopoulou MG, Strauch K, Strawbridge RJ, Suderman MJ, Tandon N, Tang ST, Taylor KD, Tayo BO, Töglhofer AM, Tomaszewski M, Tšernikova N, Tuomilehto J, Uitterlinden AG, Vaidya D, van Hylckama Vlieg A, van Setten J, Vasankari T, Vedantam S, Vlachopoulou E, Vozzi D, Vuoksimaa E, Waldenberger M, Ware EB, Wentworth-Shields W, Whitfield JB, Wild S, Willemsen G, Yajnik CS, Yao J, Zaza G, Zhu X, Project TBJ, Salem RM, Melbye M, Bisgaard H, Samani NJ, Cusi D, Mackey DA, Cooper RS, Froguel P, Pasterkamp G, Grant SFA, Hakonarson H, Ferrucci L, Scott RA, Morris AD, Palmer CNA, Dedoussis G, Deloukas P, Bertram L, Lindenberger U, Berndt SI, Lindgren CM, Timpson NJ, Tönjes A, Munroe PB, Sørensen TIA, Rotimi CN, Arnett DK, Oldehinkel AJ, Kardia SLR, Balkau B, Gambaro G, Morris AP, Eriksson JG, Wright MJ, Martin NG, Hunt SC, Starr JM, Deary IJ, Griffiths LR, Tiemeier H, Pirastu N, Kaprio J, Wareham NJ, Pérusse L, Wilson JG, Girotto G, Caulfield MJ, Raitakari O, Boomsma DI, Gieger C, van der Harst P, Hicks AA, Kraft P, Sinisalo J, Knekt P, Johannesson M, Magnusson PKE, Hamsten A, Schmidt R, Borecki IB, Vartiainen E, Becker DM, Bharadwaj D, Mohlke KL, Boehnke M, van Duijn CM, Sanghera DK, Teumer A, Zeggini E, Metspalu A, Gasparini P, Ulivi S, Ober C, Toniolo D, Rudan I, Porteous DJ, Ciullo M, Spector TD, Hayward C, Dupuis J, Loos RJF, Wright AF, Chandak GR, Vollenweider P, Shuldiner A, Ridker PM, Rotter JI, Sattar N, Gyllensten U, North KE, Pirastu M, Psaty BM, Weir DR, Laakso M, Gudnason V, Takahashi A, Chambers JC, Kooner JS, Strachan DP, Campbell H, Hirschhorn JN, Perola M, Polašek O, Wilson JF
Affiliations
  • Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.
  • Estonian Genome Center, University of Tartu, Riia 23b, 51010, Tartu, Estonia.
  • Unit of Public Health Genomics, National Institute for Health and Welfare, P.O. Box 104, Helsinki, FI-00251, Finland.
  • Department of Medical Sciences, University of Trieste, Strada di Fiume 447 - Osp. di Cattinara, Trieste, 34149, Italy.
  • Institute of Genetics and Biophysics "A. Buzzati-Traverso" CNR, via Pietro Castellino, 111, Naples, 80131, Italy.
  • Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
  • The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, 10029, USA.
  • Icelandic Heart Association, Holtasmari 1, 201, Kopavogur, Iceland.
  • Department of Epidemiology and Biostatistics, Imperial College London, Norfolk Place, London, W2 1PG, UK.
  • Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyoku, Tokyo, 113-8510, Japan.
...show more
  • Department of Medicine, University of Eastern Finland, 70210 Kuopio, Finland.
  • Institute for Social Research, University of Michigan, 426 Thompson Street, 48104, Ann Arbor, MI, USA.
  • Department of Epidemiology, University of Michigan, 1415 Washington Heights, 48109, Ann Arbor, MI, USA.
  • Cardiovascular Health Research Unit, Departments of Biostatistics and Medicine, University of Washington, 1730 Minor Ave, Suite 1360, Seattle, 98101, WA, USA.
  • Institute of Population Genetics, National Research Council, Trav. La Crucca n. 3 - Reg. Baldinca, Sassari, 07100, Italy.
  • Epidemiology, University of North Carolina, 137 E. Franklin St., Suite 306, 27599-8050, Chapel Hill, USA.
  • Immunology, Genetics & Pathology, Uppsala University, Husargatan 3, Box 815, Uppsala, SE-751 08, Sweden.
  • MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, EH4 2XU, Edinburgh, UK.
  • Department of Gerontology and Geriatrics, Leiden University Medical Center , PO Box 9600, Leiden, Netherlands.
  • Institute for Translational Genomics and Population Sciences , Los Angeles Biomedical Research Institute, 1124 W. Carson Street, Torrance, 90502, USA.
  • Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue, East, Harvard Medical School, Boston, Boston, MA 02215, USA.
  • Division of Endocrinology, Diabetes, and Nutrition and Program for Personalised and Genomic Medicine, Department of Medicine, University of Maryland School of Medicine, 685 Baltimore St. MSTF, Baltimore, 21201, USA.
  • Department of Medical Genetics, University of Lausanne, Rue du Bugnon 27, Lausanne, 1005, Switzerland.
  • Genomic Research on Complex Diseases (GRC) Group, CSIR-Centre for Cellular and Molecular Biology, Habshiguda, Uppal Road, Hyderabad, 500007, India.
  • Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue, Boston, 02118, MA, USA.
  • Department of Twin Research & Genetic Epidemiology, King's College London, South Wing, Block D, 3rd Floor, Westminster Bridge Road, London, SE1 7EH, UK.
  • Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina 58, Milano, 20132, Italy.
  • Department of Nutrition and Dietetics, Harokopio University of Athens, 70, El. Venizelou Ave, Athens, 17671, Greece.
  • Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Friedrich-Ludwig-Jahn-Str. 15A, Greifswald, 17475, Germany.
  • Center for Human Genetic Research , 55 Fruit Street, Massachusetts General Hospital, 2114, USA.
  • Department of Epidemiology, Erasmus Medical Center, PO Box 2040, Rotterdam, 3000 CA, The Netherlands.
  • Department of Genetics, University of North Carolina, Chapel Hill, 27599, NC, USA.
  • Genomics and Molecular Medicine, CSIR-Institute of Genomics & Integrative Biology, Mathura Road, New Delhi, 110025, India.
  • The GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, 21287, Maryland, USA.
  • Department of Genetics, Washington University School of Medicine, 4444 Forest Park Boulevard, Saint Louis, 63108, MO, USA.
  • Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Auenbruggerplatz 22, Graz, A-8036, Austria.
  • Erasmus School of Economics, Erasmus University Rotterdam, Burgemeester Oudlaan 50, Rotterdam, 3000 DR, The Netherlands.
  • Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, CMM L8:03, Karolinska University Hospital, Solna, Stockholm, 171 76, Sweden.
  • Channing Division of Network Medicine, Brigham & Women's Hospital, 181 Longwood, Boston, 02115, USA.
  • Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany.
  • University of Groningen, University Medical Center Groningen, Department of Cardiology, Hanzeplein 1, Groningen, 9700RB, The Netherlands.
  • Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, Neuherberg, 85764, Germany.
  • Department of Biological Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT, Amsterdam, Netherlands.
  • Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
  • Department of Medicine, University of Mississippi Medical Center, 2500 N. State St., Jackson, 39216, MS, USA.
  • Pennington Biomedical Research Center, 6400 Perkins Rd, Baton Rouge, LA 70808, USA.
  • MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
  • Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", via dell'Istria 65, Trieste, 34137, Italy.
  • Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, GPO Box 2434, Brisbane Qld 4001, Brisbane, Australia.
  • Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, 53226, WI, USA.
  • Quantitative Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, 4006, Australia.
  • Dipartimento di Scienze della Vita e della Riproduzione, University of Verona, Strada Le Grazie 15, Verona, 37134, Italy.
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK.
  • CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Lille 2 University, 1 Rue du Professeur Calmette, 59000, Lille, France.
  • Department of Biostatistics, University of Alabama at Birmingham, 1665 University Blvd, Birmingham, 35294, AL, USA.
  • Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, P.O. box 30.001, 9700 RB, Groningen, The Netherlands.
  • Center for Research on Genomics and Global Health, National Human Genome Research Institute, Building 12A/Room 4047, 12 South Dr., Bethesda, 20892, Maryland, USA.
  • MRC Integrative Epidemiology Unit, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Rockville, 20850, MD, USA.
  • Center for Lifespan Psychology, Max Planck Institute for Human Development, Lentzeallee 94, Berlin, 14195, Germany.
  • Charité Research Group on Geriatrics, Charité - Universitätsmedizin Berlin, Reinickendorferstr. 61, 13347, Berlin, Germany.
  • Division of Population Health Sciences, Medical Research Institute, University of Dundee, Ninewells hospital and School of Medicine, Dundee, DD2 4BF, Scotland.
  • William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
  • Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
  • Center for Applied Genomics, Children's Hospital of Philadelphia, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.
  • Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK.
  • Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Department of Cardiovascular Sciences, University of Leicester, BHF Cardiovascular Research Centre, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, UK.
  • Department of Health Sciences, University of Milan, via A. di Rudinì 8, 20142 Milan, Italy.
  • Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, 2 Verdun St, Perth, 6009, Australia.
  • Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, Copenhagen, 2300, Denmark.
  • Clinical Epidemiology, Leiden University Medical Center, PO Box 9600, Leiden, 2300RC, The Netherlands.
  • Department of Human Genetics, University of Chicago, 920 E. 58th Street, Chicago, IL, USA.
  • Department of Family and Preventive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, 92093, USA.
  • Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.
  • University of Groningen, University Medical Center Groningen, Department of Internal Medicine, Hanzeplein 1, Groningen, 9700RB, The Netherlands.
  • Department of Medicine, Columbia University, 622 W. 168th Street, New York, 10032, NY, USA.
  • Institute for Community Medicine, University Medicine Greifswald, W.-Rathenau-Str. 48, Greifswald, 17475, Germany.
  • Department of Economics, Cornell University, 480 Uris Hall, Ithaca, NY, 14853, USA.
  • Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, 1200 Pressler St., Suite 453E, Houston, Texas, 77030, USA.
  • Centre for Genomic and Experimental Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
  • McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, 21205, MD, USA.
  • Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Cambridge, 02141, MA, USA.
  • Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, 665 Huntington Ave, Boston, 02115, USA.
  • Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, 20892, MD, USA.
  • College of Medicine, Dentistry and Nursing, Ninewells Hospital and Medical School, College Office, Level 10, Dundee, DD1 9SY, UK.
  • Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
  • Department of Internal Medicine B, University Medicine Greifswald, Ferdinand-Sauerbruch-Str. NK, Greifswald, 17475, Germany.
  • Robertson Centre, University of Glasgow, Boyd Orr Building, Glasgow, G12 8QQ, Scotland.
  • National Heart, Lung, and Blood Institute's Framingham Heart Study, 73 Mt. Wayte Ave, Framingham, 01702, MA, USA.
  • Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Str. NK, 17475, Greifswald, Germany.
  • Epidemiology, University of North Carolina, 137 E Franklin St., Suite 306, USA.
  • Nutrition, Harvard School of Public Health, 401 Park Drive, Boston, 02215, USA.
  • Division of Biostatistics, Washington University, 660 S Euclid, St Louis, 63110, MO, USA.
  • National Institutes on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Department of Public Health, University of Helsinki, Hjelt Institute, P.O.Box 41, Mannerheimintie 172, Helsinki, FI-00014, Finland.
  • Musculoskeletal Research Programme, Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
  • State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Er Road, Shanghai, 200025 China.
  • Department of Chronic Disease Prevention, National Institute for Health and Welfare, P.O. Box 30, Helsinki, FI-00271, Finland.
  • Department of Cardiology C5-P , Leiden University Medical Center, PO Box 9600, Leiden, Netherlands.
  • Department of Clinical Physiology, University of Tampere and Tampere University Hospital, P.O. Box 2000, Tampere, 33521, Finland.
  • Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
  • Diabetes Prevention Unit, National Institute for Health and Welfare, P.O. Box 30, FI-00271 Helsinki, Finland.
  • Department of Cardiology, Ealing Hospital NHS Trust, Uxbridge Road, Southall, Middlesex, UB1 3HW, UK.
  • Laboratory for Genotyping Development RCfIMS, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
  • Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, 70210, Finland.
  • Institute of Behavioural Sciences, University of Helsinki, P.O. Box 9, FI-00014 University of Helsinki, Helsinki, Finland.
  • Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine University of Tampere, Tampere, 33520, Finland.
  • Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
  • Department of Medical Sciences, University Hospital, Uppsala, 75185, Sweden.
  • Transplantation laboratory, Haartman Institute, University of Helsinki, P.O. Box 21, Helsinki, FI-00014, Finland.
  • National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, RTP, NC, USA.
  • Ophthalmology, Massachusetts Eye and Ear, 243 Charles St, Boston, 02114, USA.
  • Department of Statistics, University of Auckland, 303.325 Science Centre, Private Bag 92019, Auckland, 1142, New Zealand.
  • Department of Health, Functional Capacity and Welfare, National Institute for Health and Welfare, P.O. Box 30, Helsinki, FI-00271, Finland.
  • Department of Internal Medicine, University Hospital, Route du Bugnon 44, Lausanne, 1011, Switzerland.
  • Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK.
  • Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
  • Division of General Internal Medicine, Massachusetts General Hospital , 50 Staniford St, Boston, 02114, MA, USA.
  • Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, Neuherberg, 85764, Germany.
  • Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, Neuherberg, 85764 Germany.
  • Molecular Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, 4006, Australia.
  • Genome Science Institute, Boston University School of Medicine, 72 East Concord Street, E-304, Boston, 2118, MA, USA.
  • HUCH Heart and Lung center, Helsinki University Central Hospital, P.O. Box 340, Helsinki, FI-00029, Finland.
  • Department of Medicine, University of Ibadan, Ibadan, Nigeria.
  • ICAMS, University of Glasgow, 126 University Way, Glasgow, G12 8TA, UK.
  • Division of Epidemiology and Community Health , University of Minnesota , 1300 S 2nd Street, Minneapolis, 55454, USA.
  • Centre for Global Health and Department of Public Health, School of Medicine, University of Split, Soltanska 2, 21000 Split, Croatia.
  • Institute for Molecular Medicine Finland (FIMM), University of Helsinki, P.O. Box 20, Helsinki, FI-00014, Finland.
  • International Centre for Circulatory Health, Imperial College London, London, W2 1LA, UK.
  • Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, SW7 2AZ, UK.
  • Department of Cardiology and Cardio thoracic Surgery Hero DMC Heart Institute, Civil Lines, 141001, Ludhiana, India.
  • Department Public Health Sciences, University of Virginia School of Medicine, 3232 West Complex, Charlottesville, 22908, USA.
  • Department of Psychological & Brain Sciences, Indiana University Bloomington, 1101 E. 10th St., Bloomington, IN 47405, USA.
  • Institute of Molecular Biology and Biochemistry, Medical University Graz, Harrachgasse 21, Graz, A-8010, Austria.
  • University of Dundee, Kirsty Semple Way, Dundee, DD2 4DB, UK.
  • Cardiovascular Health Research Unit, Division of Cardiology, University of Washington, 1730 Minor Ave, Suite 1360, Seattle, 98101, WA, USA.
  • Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland.
  • UMR INSERM U1122; IGE-PCV "Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire", INSERM, University of Lorraine, 30 Rue Lionnois, Nancy, 54000, France.
  • Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1, Neuherberg, 85764, Germany.
  • Department of Endocrinology, All India Institute of Medical Sciences, Ansari Nagar East, New Delhi, 110029, India.
  • National Heart and Lung Institute, Imperial College London, Du Cane Road, London, W12 0NN, UK.
  • Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, USA.
  • Finnish Lung Health Association, Sibeliuksenkatu 11 A 1, Helsinki, FI-00250, Finland.
  • Genetic Epidemiology, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, 4006, Australia.
  • Diabetes Unit, KEM Hospital and Research Centre, Rasta Peth, Pune, 411011, India.
  • Renal Unit, Department of Medicine, Piazzale A. Stefani 1, Verona, 37124, Italy.
  • Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, USA.
  • Translational Gerontology Branch, National institute on Aging, Baltimore, 21225, Maryland, USA.
  • Jacqui Wood Cancer Centre, Medical Research Insitute, University of Dundee, Ninewells hospital and School of Medicine, Dundee, DD1 9SY, Scotland.
  • Centre for Pharmacogenetics and Pharmacogenomics, Medical Research Institute, University of Dundee, Ninewells hospital and School of Medicine, Dundee, DD1 9SY, Scotland.
  • Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestr. 72, Berlin, 14195, Germany.
  • Program in Medical and Population Genetics, Broad Institute, Cambridge Center 7, Cambridge, 02242, MA, USA.
  • Department of Medicine, University of Leipzig, Leipzig, Germany.
  • Novo Nordisk Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, Copenhagen, 2100, Denmark.
  • Department of Epidemiology, University of Alabama at Birmingham, 1665 University Blvd, Birmingham, 35294, AL, USA.
  • Department of Psychiatry, University Medical Center Groningen, University of Groningen, P.O. box 30.001, Groningen, 9700 RB, The Netherlands.
  • Epidemiology of diabetes, obesity and chronic kidney disease over the lifecourse, Inserm, CESP Center for Research in Epidemiology and Population Health U1018, 16 Avenue Paul Vaillant Couturier, Villejuif, 94807, France.
  • Dipartimento di Scienze Mediche, Catholic University of the Sacred Heart, Via G. Moscati 31/34, Roma, 00168, Italy.
  • Neuro-Imaging Genetics, QIMR Berghofer Medical Research Institute, 300 Herston Rd, Herston, Brisbane, 4006 Australia.
  • Cardiovascular Genetics Division, University of Utah, 420 Chipeta Way, Room 1160, Salt Lake City, 84117, Utah, USA.
  • Department of kinesiology, Laval University, 2300 rue de la Terrasse, Quebec, G1V 0A6, Canada.
  • Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N. State St., Jackson, 39216, MS, USA.
  • Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, 20521, Finland.
  • Department of Economics, Stockholm School of Economics, Box 6501, Stockholm, SE-113 83, Sweden.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, Stockholm, SE-171 77, Sweden.
  • Department of Genetics and Biostatistics, Washington University School of Medicine, 4444 Forest Park Boulevard, Saint Louis, 63108, MO, USA.
  • Department of Pediatrics, University of Oklahoma Health Sciences Center, 940 Stanton Young Boulevard, Oklahoma City, 73104, OK , USA.
  • BHF centre, University of Glasgow, 126 University Avenue, Glasgow, G12 8TA, Scotland.
  • Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, 1730 Minor Ave, Suite 1360, Seattle, 98101, WA, USA.
  • Population Health Research Institute, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
Abstract

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

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