Rare and low-frequency coding variants alter human adult height.

Journal: Nature

Volume: 542

Issue: 7640

Year of Publication: 2017

Affiliated Institutions:  William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London ECM BQ, UK. Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina , USA. Department of Epidemiology, Erasmus Medical Center, Rotterdam, GE, The Netherlands. Montreal Heart Institute, Montreal, Quebec HT C, Canada. Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX DW, UK. Department of Molecular Biology and Genetics, Aarhus University, Aarhus, , Denmark. Broad Institute of MIT and Harvard, Cambridge, Massachusetts , USA. Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee , USA. The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York , USA. Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, , Switzerland. deCODE Genetics/Amgen inc., Reykjavik, , Iceland. Swiss Institute of Bioinformatics, Lausanne, , Switzerland. Department of Genetic Epidemiology, University of Regensburg, Regensburg, D-, Germany. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX BN, UK. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan , USA. Department of Cardiovascular Sciences, Univeristy of Leicester, Glenfield Hospital, Leicester LE QP, UK. Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina , USA. Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, California , USA. Netherlands Comprehensive Cancer Organisation, Utrecht, DB, The Netherlands. Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina , USA. Centre for Control of Chronic Diseases (CCCD), Dhaka, , Bangladesh. Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, D-, Germany. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, , Denmark. Department of Family Medicine &Public Health, University of California, San Diego, La Jolla, California , USA. INSERM U, Lille, F-, France. Department of Epidemiology and Public Health, University of Strasbourg, Strasbourg, F-, France. Department of Cardiology, Division Heart &Lungs, University Medical Center Utrecht, Utrecht, The Netherlands. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin , USA. INSERM U, Centre de recherche en Épidemiologie et Sante des Populations (CESP), Villejuif, France. Department of Nephrology, University Hospital Regensburg, Regensburg, , Germany. Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, , Denmark. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, , Denmark. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan , USA. IFB Adiposity Diseases, University of Leipzig, Leipzig, , Germany. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, , Germany. School of Public Health, Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas , USA. Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland , USA. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, , Denmark. MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London &NIHR Biomedical Research Centre for Mental Health at the Maudsley, London, SE AF, UK. Marshfield Clinic Research Foundation, Marshfield, Wisconsin , USA. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, GE, The Netherlands. Department of Medicine, University of Washington, Seattle, Washington , USA. MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB RN, UK. The Sigfried and Janet Weis Center for Research, Danville, Pennsylvania , USA. Department of Cardiology, London North West Healthcare NHS Trust, Ealing Hospital, Middlesex UB HW, UK. Medical Department, Lillebaelt Hospital, Vejle, , Denmark. Division of Preventive Medicine, Brigham and Women's and Harvard Medical School, Boston, Massachusetts , USA. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, , Italy. Department of Biostatistics, University of Liverpool, Liverpool L GL, UK. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH JZ, UK. Department of Human Genetics, Radboud University Medical Center, Nijmegen, HB, The Netherlands. Diamantina Institute, University of Qeensland, Brisbane, Queensland, , Australia. Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht, CX, The Netherlands. Department of Clinical Chemistry and Haematology, Division of Laboratory and Pharmacy, University Medical Center Utrecht, Utrecht, GA, The Netherlands. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, RC, The Netherlands. Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, , Greece. Division of Epidemiology &Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota , USA. Department of Ophthalmology, Radboud University Medical Center, Nijmegen, HB, The Netherlands. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB RN, UK. Institute of Cardiovascular Science, University College London, London WCE JF, UK. Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, Washington , USA. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB RN, UK. Department of Medicine, Oulu University Hospital, Oulu, , Finland. Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee , USA. Massachusetts General Hospital, Boston, Massachusetts , USA. Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W PG, UK. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W PG, UK. Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan , USA. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, StLouis, Missouri , USA. CNR Institute of Clinical Physiology, Pisa, Italy. Research Center on Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, , Italy. Toulouse University School of Medicine, Toulouse, TSA , France. University of Glasgow, Glasgow G QQ, UK. Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas , USA. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-, Sweden. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, , Denmark. Radboud University Medical Center, Nijmegen, HB, The Netherlands. Department of Medical Sciences, University of Trieste, Trieste, , Italy. Geriatrics, Department of Public Health, Uppsala University, Uppsala, , Sweden. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, , Australia. Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina , USA. Faculty of Medicine, University of Iceland, Reykjavik, , Iceland. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, , Sweden. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, Maryland , USA. University of Exeter Medical School, University of Exeter, Exeter EX DW, UK. MRCHGU, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH XU, UK. Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, North Carolina , USA. Department of Public Health, University of Helsinki, Helsinki, FI-, Finland. Department of Pediatrics, Haukeland University Hospital, Bergen, , Norway. Department of Cardiology, Heart Center, Tampere University Hospital, Tampere, , Finland. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, , Australia. Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh EH XU, UK. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, NTNU, Norwegian University of Science and Technology, Trondheim, , Norway. AMC, Department of Vascular Medicine, Amsterdam, AZ, The Netherlands. HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, , Norway. Department of Public Health &Clinical Medicine, Umeå University, Umeå, SE-, Sweden. The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, , Denmark. Department of Preventive Medicine, Keck School of Medicine of the University of California, Los Angeles, California , USA. KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, , Norway. National Institute of Public Health, University of Southern Denmark, Copenhagen, , Denmark. National Institute for Health and Welfare, Helsinki, FI-, Finland. Department of Cardiology, Leiden University Medical Center, Leiden, , The Netherlands. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan , USA. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, CG, The Netherlands. Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, , Finland. Echinos Medical Centre, Echinos, Greece. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX LE, UK. UKCRC Centre of Excellence for Public Health Research, Queens University Belfast, Belfast BT BJ, UK. Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, CX, The Netherlands. Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Greifswald, , Germany. Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, , Finland. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington , USA. German Center for Diabetes Research, München-Neuherberg, , Germany. CHU Nantes, Service de Génétique Médicale, Nantes, , France. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, , Finland. Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, , Italy. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina , USA. Department of Biostatistical Sciences and Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina , USA. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge CB QQ, UK. Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung , Taiwan. Department of Clinical Chemistry, Fimlab Laboratories, Tampere, , Finland. Division of Preventive Medicine University of Alabama at Birmingham, Birmingham, Alabama , USA. Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of China, Shanghai, , China. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, California , USA. Department of Medicine, Boston University School of Medicine, Boston, Massachusetts , USA. Uppsala University, Uppsala, , Sweden. Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina , USA. Division of Health Sciences, Warwick Medical School, Warwick University, Coventry CV AL, UK. Centre for Ophthalmology and Vision Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, , Australia. Department of Psychiatry, Washington University, Saint Louis, Missouri , USA. Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB SA, UK. Estonian Genome Center, University of Tartu, Tartu, , Estonia. Westmead Millennium Institute of Medical Research, Centre for Vision Research and Department of Ophthalmology, University of Sydney, Sydney, New South Wales, , Australia. Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH AG, UK. Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, Maryland , USA. DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, , Germany. Department of Cardiology, Heart Center, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, , Finland. Program in Personalized Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland , USA. Department of Medicine, Tampere University Hospital, Tampere, , Finland. Center for Neurobehavioral Genetics, UCLA, Los Angeles, California , USA. Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, Medical Research Institute, Ninewells Hospital and Medical School, Dundee DD SY, UK. Laboratory of Clinical Chemistry and Hematology, Division Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht, CX, The Netherlands. Department of Psychology, University of Edinburgh, Edinburgh EH JZ, UK. School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, , Australia. Center for Neurogenomics and Cognitive Research, Department Complex Trait Genetics, VU University, Amsterdam, HV, The Netherlands. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, , Finland. Centre for Non-Communicable Diseases, Karachi, Pakistan. MRL, Merck &Co., Inc., Genetics and Pharmacogenomics, Boston, Massachusetts , USA. Division of Epidemiology &Community Health University of Minnesota, Minneapolis, Minnesota , USA. Duke University, Durham, North Carolina , USA. Department of Twin Research and Genetic Epidemiology, Kingís College London, London SE EH, UK. Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, MB, The Netherlands. College of Biomedical and Life Sciences, Cardiff University, Cardiff, CF EP, UK. Institute for Community Medicine, University Medicine Greifswald, Greifswald, , Germany. Research Center for Prevention and Health, Capital Region of Denmark, Glostrup, DK-, Denmark. Center for Pediatric Research, Department for Women's and Child Health, University of Leipzig, Leipzig, , Germany. Anogia Medical Centre, Anogia, Greece. Department of Psychiatry, Dalhousie University, Halifax BH R, Canada. Laboratory of Experimental Cardiology, Division Heart &Lungs, University Medical Center Utrecht, Utrecht, CX, The Netherlands. University of Amsterdam, Department of Brain &Cognition, Amsterdam, WS, The Netherlands. USC Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California , USA. Department of Obstetrics and Gynecology, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee , USA. MRL, Merck &Co., Inc., Cardiometabolic Disease, Kenilworth, New Jersey , USA. Division of Experimental Genetics, Sidra Medical and Research Center, Doha, , Qatar. Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle NE HH, UK. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts , USA. Departments of Epidemiology &Medicine, Diabetes Translational Research Center, Fairbanks School of Public Health &School of Medicine, Indiana University, Indiana , USA. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi , USA. Danish Diabetes Academy, Odense, , Denmark. Memorial University, Faculty of Medicine, Discipline of Genetics, St. John's, Newfoundland AB V, Canada. Department of Clinical Sciences, Quantitative Biomedical Research Center, Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, Texas , USA. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania , USA. Department of Public Health Sciences, Institute for Personalized Medicine, the Pennsylvania State University College of Medicine, Hershey, Pennsylvania , USA. Department of Epidemiology and Carolina Center of Genome Sciences, Chapel Hill, North Carolina , USA. NHLBI Framingham Heart Study, Framingham, Massachusetts , USA.

Abstract summary 

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Authors & Co-authors:  Marouli Eirini E Graff Mariaelisa M Medina-Gomez Carolina C Lo Ken Sin KS Wood Andrew R AR Kjaer Troels R TR Fine Rebecca S RS Lu Yingchang Y Schurmann Claudia C Highland Heather M HM Rüeger Sina S Thorleifsson Gudmar G Justice Anne E AE Lamparter David D Stirrups Kathleen E KE Turcot Valérie V Young Kristin L KL Winkler Thomas W TW Esko Tõnu T Karaderi Tugce T Locke Adam E AE Masca Nicholas G D NG Ng Maggie C Y MC Mudgal Poorva P Rivas Manuel A MA Vedantam Sailaja S Mahajan Anubha A Guo Xiuqing X Abecasis Goncalo G Aben Katja K KK Adair Linda S LS Alam Dewan S DS Albrecht Eva E Allin Kristine H KH Allison Matthew M Amouyel Philippe P Appel Emil V EV Arveiler Dominique D Asselbergs Folkert W FW Auer Paul L PL Balkau Beverley B Banas Bernhard B Bang Lia E LE Benn Marianne M Bergmann Sven S Bielak Lawrence F LF Blüher Matthias M Boeing Heiner H Boerwinkle Eric E Böger Carsten A CA Bonnycastle Lori L LL Bork-Jensen Jette J Bots Michiel L ML Bottinger Erwin P EP Bowden Donald W DW Brandslund Ivan I Breen Gerome G Brilliant Murray H MH Broer Linda L Burt Amber A AA Butterworth Adam S AS Carey David J DJ Caulfield Mark J MJ Chambers John C JC Chasman Daniel I DI Chen Yii-Der Ida YI Chowdhury Rajiv R Christensen Cramer C Chu Audrey Y AY Cocca Massimiliano M Collins Francis S FS Cook James P JP Corley Janie J Galbany Jordi Corominas JC Cox Amanda J AJ Cuellar-Partida Gabriel G Danesh John J Davies Gail G de Bakker Paul I W PI de Borst Gert J GJ de Denus Simon S de Groot Mark C H MC de Mutsert Renée R Deary Ian J IJ Dedoussis George G Demerath Ellen W EW den Hollander Anneke I AI Dennis Joe G JG Di Angelantonio Emanuele E Drenos Fotios F Du Mengmeng M Dunning Alison M AM Easton Douglas F DF Ebeling Tapani T Edwards Todd L TL Ellinor Patrick T PT Elliott Paul P Evangelou Evangelos E Farmaki Aliki-Eleni AE Faul Jessica D JD Feitosa Mary F MF Feng Shuang S Ferrannini Ele E Ferrario Marco M MM Ferrieres Jean J Florez Jose C JC Ford Ian I Fornage Myriam M Franks Paul W PW Frikke-Schmidt Ruth R Galesloot Tessel E TE Gan Wei W Gandin Ilaria I Gasparini Paolo P Giedraitis Vilmantas V Giri Ayush A Girotto Giorgia G Gordon Scott D SD Gordon-Larsen Penny P Gorski Mathias M Grarup Niels N Grove Megan L ML Gudnason Vilmundur V Gustafsson Stefan S Hansen Torben T Harris Kathleen Mullan KM Harris Tamara B TB Hattersley Andrew T AT Hayward Caroline C He Liang L Heid Iris M IM Heikkilä Kauko K Helgeland Øyvind Ø Hernesniemi Jussi J Hewitt Alex W AW Hocking Lynne J LJ Hollensted Mette M Holmen Oddgeir L OL Hovingh G Kees GK Howson Joanna M M JM Hoyng Carel B CB Huang Paul L PL Hveem Kristian K Ikram M Arfan MA Ingelsson Erik E Jackson Anne U AU Jansson Jan-Håkan JH Jarvik Gail P GP Jensen Gorm B GB Jhun Min A MA Jia Yucheng Y Jiang Xuejuan X Johansson Stefan S Jørgensen Marit E ME Jørgensen Torben T Jousilahti Pekka P Jukema J Wouter JW Kahali Bratati B Kahn René S RS Kähönen Mika M Kamstrup Pia R PR Kanoni Stavroula S Kaprio Jaakko J Karaleftheri Maria M Kardia Sharon L R SL Karpe Fredrik F Kee Frank F Keeman Renske R Kiemeney Lambertus A LA Kitajima Hidetoshi H Kluivers Kirsten B KB Kocher Thomas T Komulainen Pirjo P Kontto Jukka J Kooner Jaspal S JS Kooperberg Charles C Kovacs Peter P Kriebel Jennifer J Kuivaniemi Helena H Küry Sébastien S Kuusisto Johanna J La Bianca Martina M Laakso Markku M Lakka Timo A TA Lange Ethan M EM Lange Leslie A LA Langefeld Carl D CD Langenberg Claudia C Larson Eric B EB Lee I-Te IT Lehtimäki Terho T Lewis Cora E CE Li Huaixing H Li Jin J Li-Gao Ruifang R Lin Honghuang H Lin Li-An LA Lin Xu X Lind Lars L Lindström Jaana J Linneberg Allan A Liu Yeheng Y Liu Yongmei Y Lophatananon Artitaya A Luan Jian'an J Lubitz Steven A SA Lyytikäinen Leo-Pekka LP Mackey David A DA Madden Pamela A F PA Manning Alisa K AK Männistö Satu S Marenne Gaëlle G Marten Jonathan J Martin Nicholas G NG Mazul Angela L AL Meidtner Karina K Metspalu Andres A Mitchell Paul P Mohlke Karen L KL Mook-Kanamori Dennis O DO Morgan Anna A Morris Andrew D AD Morris Andrew P AP Müller-Nurasyid Martina M Munroe Patricia B PB Nalls Mike A MA Nauck Matthias M Nelson Christopher P CP Neville Matt M Nielsen Sune F SF Nikus Kjell K Njølstad Pål R PR Nordestgaard Børge G BG Ntalla Ioanna I O'Connel Jeffrey R JR Oksa Heikki H Loohuis Loes M Olde LM Ophoff Roel A RA Owen Katharine R KR Packard Chris J CJ Padmanabhan Sandosh S Palmer Colin N A CN Pasterkamp Gerard G Patel Aniruddh P AP Pattie Alison A Pedersen Oluf O Peissig Peggy L PL Peloso Gina M GM Pennell Craig E CE Perola Markus M Perry James A JA Perry John R B JR Person Thomas N TN Pirie Ailith A Polasek Ozren O Posthuma Danielle D Raitakari Olli T OT Rasheed Asif A Rauramaa Rainer R Reilly Dermot F DF Reiner Alex P AP Renström Frida F Ridker Paul M PM Rioux John D JD Robertson Neil N Robino Antonietta A Rolandsson Olov O Rudan Igor I Ruth Katherine S KS Saleheen Danish D Salomaa Veikko V Samani Nilesh J NJ Sandow Kevin K Sapkota Yadav Y Sattar Naveed N Schmidt Marjanka K MK Schreiner Pamela J PJ Schulze Matthias B MB Scott Robert A RA Segura-Lepe Marcelo P MP Shah Svati S Sim Xueling X Sivapalaratnam Suthesh S Small Kerrin S KS Smith Albert Vernon AV Smith Jennifer A JA Southam Lorraine L Spector Timothy D TD Speliotes Elizabeth K EK Starr John M JM Steinthorsdottir Valgerdur V Stringham Heather M HM Stumvoll Michael M Surendran Praveen P 't Hart Leen M LM Tansey Katherine E KE Tardif Jean-Claude JC Taylor Kent D KD Teumer Alexander A Thompson Deborah J DJ Thorsteinsdottir Unnur U Thuesen Betina H BH Tönjes Anke A Tromp Gerard G Trompet Stella S Tsafantakis Emmanouil E Tuomilehto Jaakko J Tybjaerg-Hansen Anne A Tyrer Jonathan P JP Uher Rudolf R Uitterlinden André G AG Ulivi Sheila S van der Laan Sander W SW Van Der Leij Andries R AR van Duijn Cornelia M CM van Schoor Natasja M NM van Setten Jessica J Varbo Anette A Varga Tibor V TV Varma Rohit R Edwards Digna R Velez DR Vermeulen Sita H SH Vestergaard Henrik H Vitart Veronique V Vogt Thomas F TF Vozzi Diego D Walker Mark M Wang Feijie F Wang Carol A CA Wang Shuai S Wang Yiqin Y Wareham Nicholas J NJ Warren Helen R HR Wessel Jennifer J Willems Sara M SM Wilson James G JG Witte Daniel R DR Woods Michael O MO Wu Ying Y Yaghootkar Hanieh H Yao Jie J Yao Pang P Yerges-Armstrong Laura M LM Young Robin R Zeggini Eleftheria E Zhan Xiaowei X Zhang Weihua W Zhao Jing Hua JH Zhao Wei W Zhao Wei W Zheng He H Zhou Wei W Rotter Jerome I JI Boehnke Michael M Kathiresan Sekar S McCarthy Mark I MI Willer Cristen J CJ Stefansson Kari K Borecki Ingrid B IB Liu Dajiang J DJ North Kari E KE Heard-Costa Nancy L NL Pers Tune H TH Lindgren Cecilia M CM Oxvig Claus C Kutalik Zoltán Z Rivadeneira Fernando F Loos Ruth J F RJ Frayling Timothy M TM Hirschhorn Joel N JN Deloukas Panos P Lettre Guillaume G

Study Outcome 

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Citations :  Fisher RA. The Correlation Between Relatives on the Supposition of Mendelian Inheritance. Transactions of the Royal Society of Edinburgh. 1918;52:399–433.
Authors :  380
Identifiers
Doi : 10.1038/nature21039
SSN : 1476-4687
Study Population
Male,Female
Mesh Terms
ADAMTS Proteins
Other Terms
Study Design
Cross Sectional Study
Study Approach
Country of Study
Publication Country
England