Rare and low-frequency coding variants alter human adult height
Marouli, Eirini (författare)
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.,Queen Mary University
Graff, Mariaelisa (författare)
Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.,North Carolina State University
Medina-Gomez, Carolina (författare)
Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.,Erasmus University Medical Center
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.,Boston Children's Hospital
Lu, Yingchang (författare)
Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA.,Icahn School of Medicine at Mount Sinai
Schurmann, Claudia (författare)
Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA.,Icahn School of Medicine at Mount Sinai
Highland, Heather M. (författare)
Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.;Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Univ Texas Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Univ Cambridge, Dept Hematol, Cambridge CB2 0PT, England.,University of Cambridge
Turcot, Valerie (författare)
Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
Young, Kristin L. (författare)
Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.,North Carolina State University
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
Karaderi, Tugce (författare)
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.,University of Oxford
Locke, Adam E. (författare)
Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO 63108 USA.,University of Washington
Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.,Wake Forest University
Mudgal, Poorva (författare)
Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.,Wake Forest University
Rivas, Manuel A. (författare)
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Nuffield Dept Clin Med, Oxford OX3 7BN, England.
Vedantam, Sailaja (författare)
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.,Boston Children's Hospital
Mahajan, Anubha (författare)
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.,University of Oxford
Guo, Xiuqing (författare)
LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.,Harbor–UCLA Medical Center
Abecasis, Goncalo (författare)
Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.,Michigan Technological University
Aben, Katja K. (författare)
Netherland Comprehens Canc Org, NL-3501 DB Utrecht, Netherlands.;Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands.
Adair, Linda S. (författare)
Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.,North Carolina State University
Alam, Dewan S. (författare)
Ctr Control Chron Dis, Dhaka 1212, Bangladesh.,Centre for Control of Chronic Diseases (CCCD)
Albrecht, Eva (författare)
Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.,Helmholtz Zentrum München
Allin, Kristine H. (författare)
Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark.,Hagedorn Research Institute, Copenhagen University
Allison, Matthew (författare)
Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA.,San Diego State University
Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark.,Hagedorn Research Institute, Copenhagen University
Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England.;NIHR Biomed Res Ctr Mental Hlth Maudsley, London SE5 8AF, England.
Brilliant, Murray H. (författare)
Marshfield Clin Res Fdn, Marshfield, WI 54449 USA.
Broer, Linda (författare)
Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
Burt, Amber A. (författare)
Univ Washington, Dept Med, Seattle, WA 98195 USA.
Butterworth, Adam S. (författare)
Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England.
Carey, David J. (författare)
Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.
Caulfield, Mark J. (författare)
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England.
Chambers, John C. (författare)
London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ London Imperial Coll Sci Technol & Med, Healthcare NHS Trust, London W12 0HS, England.
Chasman, Daniel I. (författare)
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.
Chen, Yii-Der Ida (författare)
LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
Chowdhury, Rajiv (författare)
Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.
Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England.
Drenos, Fotios (författare)
UCL, Inst Cardiovasc Sci, London WC1E 6JF, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.
Du, Mengmeng (författare)
Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.
Gasparini, Paolo (författare)
Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.;Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar.
Giedraitis, Vilmantas (författare)
Uppsala universitet,Geriatrik
Giri, Ayush (författare)
Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Med,Div Epidemiol, Nashville, TN 37203 USA.
Girotto, Giorgia (författare)
Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.;Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar.
Gordon, Scott D. (författare)
QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
Gordon-Larsen, Penny (författare)
Univ N Carolina, Caroline Populat Ctr, Chapel Hill, NC 27514 USA.;Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA.
Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA.
Kahn, Rene S. (författare)
Ctr Med Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands.
Kahonen, Mika (författare)
Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland.
German Ctr Diabet Res, D-85764 Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany.
Kuivaniemi, Helena (författare)
Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Dept Psychiat, ZA-7505 Tygerberg, Western Cape, South Africa.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, ZA-7505 Tygerberg, Western Cape, South Africa.
Kury, Sebastien (författare)
CHU Nantes, Serv Genet Med, F-44093 Nantes, France.
Univ Washington, Dept Med, Seattle, WA 98195 USA.;Grp Hlth Res Inst, Seattle, WA 98101 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA.
Lee, I-Te (författare)
Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung 407, Taiwan.;Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.;Chung Shan Med Univ, Sch Med, Taichung 402, Taiwan.
Lehtimaki, Terho (författare)
Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland.
Lewis, Cora E. (författare)
Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35205 USA.
Li, Huaixing (författare)
Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China.
Li, Jin (författare)
Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Palo Alto, CA 94305 USA.
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England.
Mueller-Nurasyid, Martina (författare)
Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Univ Munich, Dept Med 1, D-81377 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany.
Munroe, Patricia B. (författare)
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England.
Nalls, Mike A. (författare)
NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
Nauck, Matthias (författare)
DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.;Univ Med Greifswald, Inst Clin Chem, D-17475 Greifswald, Germany.;Univ Med Greifswald, Lab Med, D-17475 Greifswald, Germany.
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.
O'Connel, Jeffrey R. (författare)
Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA.
Oksa, Heikki (författare)
Tampere Univ Hosp, Dept Med, Tampere 33521, Finland.
Loohuis, Loes M. Olde (författare)
Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA.
Ophoff, Roel A. (författare)
Ctr Med Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands.;Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA.
Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
Rioux, John D. (författare)
Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada.
Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
Speliotes, Elizabeth K. (författare)
Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA.
Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Human Genet & Mol Biol, ZA-7505 Tygerberg, Western Cape, South Africa.
Trompet, Stella (författare)
Leiden Univ Med Ctr, Dept Cardiol, NL-2333 Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2333 Leiden, Netherlands.
Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
Varma, Rohit (författare)
Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90089 USA.
Edwards, Digna R. Velez (författare)
Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Obstet & Gynecol, Nashville, TN 37203 USA.
Vermeulen, Sita H. (författare)
Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands.
Vestergaard, Henrik (författare)
Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark.
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England.
Wessel, Jennifer (författare)
Indiana Univ, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Dept Epidemiol & Med, Indianapolis, IN 46202 USA.;Indiana Univ, Sch Med, Indianapolis, IN 46202 USA.
Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.
Loos, Ruth J. F. (författare)
Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10069 USA.
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Harvard Med Sch, Dept Pediat & Genet, Boston, MA 02115 USA.
Deloukas, Panos (författare)
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia.
Lettre, Guillaume (författare)
Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada.
Umeå University,Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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.
Ämnesord
MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskaper -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Health Sciences (hsv//eng)