Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

doi:10.1016/j.ajhg.2021.02.011

. 2021 Apr 1;108(4):564-582.

doi: 10.1016/j.ajhg.2021.02.011. Epub 2021 Mar 12.

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Mariaelisa Graff¹, Anne E Justice², Kristin L Young³, Eirini Marouli⁴, Xinruo Zhang³, Rebecca S Fine⁵, Elise Lim⁶, Victoria Buchanan³, Kristin Rand⁷, Mary F Feitosa⁸, Mary K Wojczynski⁸, Lisa R Yanek⁹, Yaming Shao³, Rebecca Rohde³, Adebowale A Adeyemo¹⁰, Melinda C Aldrich¹¹, Matthew A Allison¹², Christine B Ambrosone¹³, Stefan Ambs¹⁴, Christopher Amos¹⁵, Donna K Arnett¹⁶, Larry Atwood¹⁷, Elisa V Bandera¹⁸, Traci Bartz¹⁹, Diane M Becker⁹, Sonja I Berndt²⁰, Leslie Bernstein²¹, Lawrence F Bielak²², William J Blot²³, Erwin P Bottinger²⁴, Donald W Bowden²⁵, Jonathan P Bradfield²⁶, Jennifer A Brody²⁷, Ulrich Broeckel²⁸, Gregory Burke²⁹, Brian E Cade³⁰, Qiuyin Cai³¹, Neil Caporaso²⁰, Chris Carlson³², John Carpten³³, Graham Casey³⁴, Stephen J Chanock²⁰, Guanjie Chen¹⁰, Minhui Chen³⁵, Yii-Der I Chen³⁶, Wei-Min Chen³⁷, Alessandra Chesi³⁸, Charleston W K Chiang³⁵, Lisa Chu³⁹, Gerry A Coetzee⁴⁰, David V Conti⁷, Richard S Cooper⁴¹, Mary Cushman⁴², Ellen Demerath⁴³, Sandra L Deming³¹, Latchezar Dimitrov⁴⁴, Jingzhong Ding⁴⁵, W Ryan Diver⁴⁶, Qing Duan⁴⁷, Michele K Evans⁴⁸, Adeyinka G Falusi⁴⁹, Jessica D Faul⁵⁰, Myriam Fornage⁵¹, Caroline Fox⁵², Barry I Freedman⁵³, Melissa Garcia⁵⁴, Elizabeth M Gillanders⁵⁵, Phyllis Goodman⁵⁶, Omri Gottesman²⁴, Struan F A Grant⁵⁷, Xiuqing Guo³⁶, Hakon Hakonarson⁵⁸, Talin Haritunians⁵⁹, Tamara B Harris⁶⁰, Curtis C Harris¹⁴, Brian E Henderson³⁴, Anselm Hennis⁶¹, Dena G Hernandez⁶², Joel N Hirschhorn⁶³, Lorna Haughton McNeill⁶⁴, Timothy D Howard⁴⁴, Barbara Howard⁶⁵, Ann W Hsing⁶⁶, Yu-Han H Hsu⁶³, Jennifer J Hu⁶⁷, Chad D Huff¹⁵, Dezheng Huo⁶⁸, Sue A Ingles³⁴, Marguerite R Irvin⁶⁹, Esther M John⁷⁰, Karen C Johnson⁷¹, Joanne M Jordan⁷², Edmond K Kabagambe⁶⁹, Sun J Kang⁷³, Sharon L Kardia²², Brendan J Keating⁷⁴, Rick A Kittles⁷⁵, Eric A Klein⁷⁶, Suzanne Kolb³², Laurence N Kolonel⁷⁷, Charles Kooperberg³², Lewis Kuller⁷⁸, Abdullah Kutlar⁷⁹, Leslie Lange⁸⁰, Carl D Langefeld⁸¹, Loic Le Marchand⁷⁷, Hampton Leonard⁸², Guillaume Lettre⁸³, Albert M Levin⁸⁴, Yun Li⁸⁵, Jin Li⁸⁶, Yongmei Liu⁸⁷, Youfang Liu⁷², Simin Liu⁸⁸, Kurt Lohman⁸¹, Vaneet Lotay²⁴, Yingchang Lu⁸⁹, William Maixner⁹⁰, JoAnn E Manson⁹¹, Barbara McKnight¹⁹, Yan Meng⁹², Keri L Monda⁹³, Kris Monroe⁷, Jason H Moore⁹⁴, Thomas H Mosley⁹⁵, Poorva Mudgal⁹⁶, Adam B Murphy⁹⁷, Rajiv Nadukuru²⁴, Mike A Nalls⁸², Katherine L Nathanson⁹⁸, Uma Nayak³⁷, Amidou N'Diaye⁹⁹, Barbara Nemesure¹⁰⁰, Christine Neslund-Dudas⁸⁴, Marian L Neuhouser³², Sarah Nyante¹⁰¹, Heather Ochs-Balcom¹⁰², Temidayo O Ogundiran¹⁰³, Adesola Ogunniyi¹⁰⁴, Oladosu Ojengbede¹⁰⁵, Hayrettin Okut⁹⁶, Olufunmilayo I Olopade¹⁰⁶, Andrew Olshan¹⁰¹, Badri Padhukasahasram¹⁰⁷, Julie Palmer¹⁰⁸, Cameron D Palmer¹⁰⁹, Nicholette D Palmer¹¹⁰, George Papanicolaou¹¹¹, Sanjay R Patel¹¹², Curtis A Pettaway¹¹³, Patricia A Peyser²², Michael F Press¹¹⁴, D C Rao¹¹⁵, Laura J Rasmussen-Torvik¹¹⁶, Susan Redline⁹¹, Alex P Reiner³², Suhn K Rhie³⁴, Jorge L Rodriguez-Gil⁶⁷, Charles N Rotimi¹⁰, Jerome I Rotter³⁶, Edward A Ruiz-Narvaez¹¹⁷, Benjamin A Rybicki⁸⁴, Babatunde Salako¹⁰⁵, Michele M Sale³⁷, Maureen Sanderson¹¹⁸, Eric Schadt¹¹⁹, Pamela J Schreiner⁴³, Claudia Schurmann²⁴, Ann G Schwartz¹²⁰, Daniel A Shriner¹⁰, Lisa B Signorello²³, Andrew B Singleton⁶², David S Siscovick¹²¹, Jennifer A Smith¹²², Shad Smith⁹⁰, Elizabeth Speliotes¹²³, Margaret Spitz¹⁵, Janet L Stanford¹²⁴, Victoria L Stevens⁴⁶, Alex Stram⁷, Sara S Strom¹⁵, Lara Sucheston¹³, Yan V Sun¹²⁵, Salman M Tajuddin⁵⁴, Herman Taylor⁹⁵, Kira Taylor¹²⁶, Bamidele O Tayo⁴¹, Michael J Thun⁴⁶, Margaret A Tucker²⁰, Dhananjay Vaidya¹²⁷, David J Van Den Berg³⁴, Sailaja Vedantam¹⁰⁹, Mara Vitolins²⁹, Zhaoming Wang¹²⁸, Erin B Ware¹²², Sylvia Wassertheil-Smoller¹²⁹, David R Weir⁵⁰, John K Wiencke¹³⁰, Scott M Williams¹³¹, L Keoki Williams¹³², James G Wilson¹³³, John S Witte¹³⁴, Margaret Wrensch¹³⁵, Xifeng Wu¹⁵, Jie Yao³⁶, Neil Zakai⁴², Krista Zanetti⁵⁵, Babette S Zemel¹³⁶, Wei Zhao²², Jing Hua Zhao¹³⁷, Wei Zheng³¹, Degui Zhi¹³⁸, Jie Zhou¹⁰, Xiaofeng Zhu¹³¹, Regina G Ziegler²⁰, Joe Zmuda⁷⁸, Alan B Zonderman⁶⁰, Bruce M Psaty²⁷, Ingrid B Borecki¹³⁹, L Adrienne Cupples¹⁴⁰, Ching-Ti Liu⁶, Christopher A Haiman³⁴, Ruth Loos¹⁴¹, Maggie C Y Ng¹⁴², Kari E North³

Affiliations

¹ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: [email protected].
² Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Population Health Services, Geisinger Health, Danville, PA 17822, USA.
³ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK; Centre for Genomic Health, Life Sciences, Queen Mary University of London, London EC1M 6BQ, UK.
⁵ Vertex Pharmaceuticals Inc., Boston, MA 02210, USA.
⁶ Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
⁷ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
⁸ Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA.
⁹ Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
¹⁰ Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹¹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Thoracic Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
¹² Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA 92093, USA.
¹³ Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
¹⁴ Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹⁵ Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁶ School of Public Health, University of Kentucky, Lexington, KY 40563, USA.
¹⁷ Framingham Heart Study, Boston University School of Medicine, Boston, MA 02118, USA.
¹⁸ Department of Population Science, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
¹⁹ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
²⁰ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
²¹ Division of Biomarkers of Early Detection and Prevention, Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
²² Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
²³ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; International Epidemiology Institute, Rockville, MD 20850, USA.
²⁴ The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
²⁵ Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Center for Diabetes Research, Wake Forest school of Medicine, Winston-Salem, NC 27157, USA.
²⁶ Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
²⁷ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
²⁸ Department of Pediatrics, Section of Genomic Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
²⁹ Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
³⁰ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
³¹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
³² Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
³³ Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
³⁴ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
³⁵ Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
³⁶ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
³⁷ Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
³⁸ Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
³⁹ Cancer Prevention Institute of California, Fremont, CA 94538, USA.
⁴⁰ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, LA 90033, USA.
⁴¹ Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA.
⁴² Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA.
⁴³ Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN 55455, USA.
⁴⁴ Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
⁴⁵ Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
⁴⁶ Epidemiology Research Program, American Cancer Society, Atlanta, GA 30303, USA.
⁴⁷ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴⁸ Health Disparities Research Section, Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
⁴⁹ Institute for Medical Research and Training, University of Ibadan, Ibadan, Nigeria.
⁵⁰ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA.
⁵¹ Center for Human Genetics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
⁵² Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; Framingham Heart Study, Framingham, MA 01702, USA; Division of Endocrinology and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁵³ Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
⁵⁴ National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
⁵⁵ Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD 20892, USA.
⁵⁶ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
⁵⁷ Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia Research Institute, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
⁵⁸ Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
⁵⁹ Medical Genetics Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA.
⁶⁰ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
⁶¹ Department of Preventive Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Chronic Disease Research Centre and Faculty of Medical Sciences, University of West Indies, Bridgetown, Barbados; Ministry of Health, Bridgetown, Barbados.
⁶² Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA.
⁶³ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
⁶⁴ Department of Health Disparities Research, Division of OVP, Cancer Prevention and Population Sciences, and Center for Community Implementation and Dissemination Research, Duncan Family Institute, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁶⁵ MedStar Research Institute, Hyattsville, MD 20782, USA.
⁶⁶ Cancer Prevention Institute of California, Fremont, CA 94538, USA; Department of Medicine, Stanford Prevention Research Center and Cancer Institute, Stanford, CA 94305, USA.
⁶⁷ Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
⁶⁸ Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA.
⁶⁹ Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁷⁰ Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94304, USA.
⁷¹ Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
⁷² Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁷³ Genetic Epidemiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
⁷⁴ Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁷⁵ Division of Health Equities, Department of Population Sciences, City of Hope Medical Center, Duarte, CA 91010, USA.
⁷⁶ Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
⁷⁷ Epidemiology Program, Cancer Research Center, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
⁷⁸ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
⁷⁹ Sickle Cell Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
⁸⁰ Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁸¹ Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
⁸² Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA; Data Tecnica Int'l, LLC, Glen Echo, MD 20812, USA.
⁸³ Montreal Heart Institute, Montréal, QC H1T 1C8, Canada; Department of Medicine, Université de Montréal, Montréal, QC H1T 1C8, Canada.
⁸⁴ Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202, USA.
⁸⁵ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁸⁶ Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
⁸⁷ Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA.
⁸⁸ Department of Epidemiology, Brown University, Providence, RI 02912, USA.
⁸⁹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁹⁰ Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
⁹¹ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁹² Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
⁹³ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; The Center for Observational Research, Amgen, Inc., Thousand Oaks, CA 91320, USA.
⁹⁴ Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁹⁵ Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
⁹⁶ Center for Diabetes Research, Wake Forest school of Medicine, Winston-Salem, NC 27157, USA.
⁹⁷ Department of Urology, Northwestern University, Chicago, IL 60611, USA.
⁹⁸ Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁹⁹ Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.
¹⁰⁰ Department of Preventive Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
¹⁰¹ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
¹⁰² Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY 14214, USA.
¹⁰³ Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria.
¹⁰⁴ Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria.
¹⁰⁵ Centre for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria.
¹⁰⁶ Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, IL 60637, USA.
¹⁰⁷ Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI 48202, USA.
¹⁰⁸ Slone Epidemiology Center, Boston University School of Medicine, Boston, MA 02118, USA.
¹⁰⁹ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA 02115, USA.
¹¹⁰ Department of Biochemistry, School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
¹¹¹ Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹¹² Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
¹¹³ Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
¹¹⁴ Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
¹¹⁵ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA.
¹¹⁶ Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
¹¹⁷ Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
¹¹⁸ Department of Family and Community Medicine, Meharry Medical College, Nashville, TN 37208, USA.
¹¹⁹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹²⁰ Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Karmanos Cancer Institute, Detroit, MI 48201, USA.
¹²¹ The New York Academy of Medicine, New York, NY 10029, USA.
¹²² Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA.
¹²³ Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
¹²⁴ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Epidemiology, University of Washington School of Public Health, Seattle, WA 98195, USA.
¹²⁵ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
¹²⁶ Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, Louisville, KY 40202, USA.
¹²⁷ Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
¹²⁸ Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
¹²⁹ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
¹³⁰ Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
¹³¹ Departments of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
¹³² Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI 48202, USA; Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USA.
¹³³ Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
¹³⁴ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA.
¹³⁵ Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA.
¹³⁶ Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA 19146, USA.
¹³⁷ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
¹³⁸ School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
¹³⁹ Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA; BioData Catalyst Program, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
¹⁴⁰ Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA; Framingham Heart Study, Boston University School of Medicine, Boston, MA 02118, USA.
¹⁴¹ The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mindich Child Health Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁴² Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Center for Diabetes Research, Wake Forest school of Medicine, Winston-Salem, NC 27157, USA.

PMID: 33713608
PMCID: PMC8059339
DOI: 10.1016/j.ajhg.2021.02.011

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Mariaelisa Graff et al. Am J Hum Genet. 2021.

. 2021 Apr 1;108(4):564-582.

doi: 10.1016/j.ajhg.2021.02.011. Epub 2021 Mar 12.

Authors

Affiliations

¹ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: [email protected].
² Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Population Health Services, Geisinger Health, Danville, PA 17822, USA.
³ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK; Centre for Genomic Health, Life Sciences, Queen Mary University of London, London EC1M 6BQ, UK.
⁵ Vertex Pharmaceuticals Inc., Boston, MA 02210, USA.
⁶ Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
⁷ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
⁸ Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA.
⁹ Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
¹⁰ Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹¹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Thoracic Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
¹² Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA 92093, USA.
¹³ Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
¹⁴ Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹⁵ Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁶ School of Public Health, University of Kentucky, Lexington, KY 40563, USA.
¹⁷ Framingham Heart Study, Boston University School of Medicine, Boston, MA 02118, USA.
¹⁸ Department of Population Science, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
¹⁹ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA; Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
²⁰ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
²¹ Division of Biomarkers of Early Detection and Prevention, Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
²² Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
²³ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; International Epidemiology Institute, Rockville, MD 20850, USA.
²⁴ The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
²⁵ Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Center for Diabetes Research, Wake Forest school of Medicine, Winston-Salem, NC 27157, USA.
²⁶ Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
²⁷ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
²⁸ Department of Pediatrics, Section of Genomic Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
²⁹ Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
³⁰ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
³¹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
³² Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
³³ Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
³⁴ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
³⁵ Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
³⁶ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
³⁷ Department of Public Health Sciences and Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
³⁸ Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
³⁹ Cancer Prevention Institute of California, Fremont, CA 94538, USA.
⁴⁰ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, LA 90033, USA.
⁴¹ Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA.
⁴² Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405, USA.
⁴³ Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN 55455, USA.
⁴⁴ Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
⁴⁵ Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
⁴⁶ Epidemiology Research Program, American Cancer Society, Atlanta, GA 30303, USA.
⁴⁷ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴⁸ Health Disparities Research Section, Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
⁴⁹ Institute for Medical Research and Training, University of Ibadan, Ibadan, Nigeria.
⁵⁰ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA.
⁵¹ Center for Human Genetics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
⁵² Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA; Framingham Heart Study, Framingham, MA 01702, USA; Division of Endocrinology and Metabolism, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁵³ Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
⁵⁴ National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
⁵⁵ Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD 20892, USA.
⁵⁶ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
⁵⁷ Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Center for Spatial and Functional Genomics, The Children's Hospital of Philadelphia Research Institute, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
⁵⁸ Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
⁵⁹ Medical Genetics Institute, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA.
⁶⁰ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
⁶¹ Department of Preventive Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Chronic Disease Research Centre and Faculty of Medical Sciences, University of West Indies, Bridgetown, Barbados; Ministry of Health, Bridgetown, Barbados.
⁶² Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA.
⁶³ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
⁶⁴ Department of Health Disparities Research, Division of OVP, Cancer Prevention and Population Sciences, and Center for Community Implementation and Dissemination Research, Duncan Family Institute, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁶⁵ MedStar Research Institute, Hyattsville, MD 20782, USA.
⁶⁶ Cancer Prevention Institute of California, Fremont, CA 94538, USA; Department of Medicine, Stanford Prevention Research Center and Cancer Institute, Stanford, CA 94305, USA.
⁶⁷ Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
⁶⁸ Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA.
⁶⁹ Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁷⁰ Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA 94304, USA.
⁷¹ Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
⁷² Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁷³ Genetic Epidemiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
⁷⁴ Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁷⁵ Division of Health Equities, Department of Population Sciences, City of Hope Medical Center, Duarte, CA 91010, USA.
⁷⁶ Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
⁷⁷ Epidemiology Program, Cancer Research Center, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
⁷⁸ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
⁷⁹ Sickle Cell Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
⁸⁰ Division of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁸¹ Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
⁸² Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA; Data Tecnica Int'l, LLC, Glen Echo, MD 20812, USA.
⁸³ Montreal Heart Institute, Montréal, QC H1T 1C8, Canada; Department of Medicine, Université de Montréal, Montréal, QC H1T 1C8, Canada.
⁸⁴ Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202, USA.
⁸⁵ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁸⁶ Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
⁸⁷ Department of Medicine, Division of Cardiology, Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA.
⁸⁸ Department of Epidemiology, Brown University, Providence, RI 02912, USA.
⁸⁹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁹⁰ Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
⁹¹ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁹² Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
⁹³ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; The Center for Observational Research, Amgen, Inc., Thousand Oaks, CA 91320, USA.
⁹⁴ Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁹⁵ Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
⁹⁶ Center for Diabetes Research, Wake Forest school of Medicine, Winston-Salem, NC 27157, USA.
⁹⁷ Department of Urology, Northwestern University, Chicago, IL 60611, USA.
⁹⁸ Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁹⁹ Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.
¹⁰⁰ Department of Preventive Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
¹⁰¹ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
¹⁰² Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY 14214, USA.
¹⁰³ Department of Surgery, College of Medicine, University of Ibadan, Ibadan, Nigeria.
¹⁰⁴ Department of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria.
¹⁰⁵ Centre for Population and Reproductive Health, College of Medicine, University of Ibadan, Ibadan, Nigeria.
¹⁰⁶ Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, IL 60637, USA.
¹⁰⁷ Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI 48202, USA.
¹⁰⁸ Slone Epidemiology Center, Boston University School of Medicine, Boston, MA 02118, USA.
¹⁰⁹ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA 02115, USA.
¹¹⁰ Department of Biochemistry, School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
¹¹¹ Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
¹¹² Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA.
¹¹³ Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
¹¹⁴ Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
¹¹⁵ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA.
¹¹⁶ Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
¹¹⁷ Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
¹¹⁸ Department of Family and Community Medicine, Meharry Medical College, Nashville, TN 37208, USA.
¹¹⁹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹²⁰ Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Karmanos Cancer Institute, Detroit, MI 48201, USA.
¹²¹ The New York Academy of Medicine, New York, NY 10029, USA.
¹²² Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI 48104, USA.
¹²³ Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
¹²⁴ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Epidemiology, University of Washington School of Public Health, Seattle, WA 98195, USA.
¹²⁵ Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
¹²⁶ Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, Louisville, KY 40202, USA.
¹²⁷ Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
¹²⁸ Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
¹²⁹ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
¹³⁰ Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
¹³¹ Departments of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
¹³² Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI 48202, USA; Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USA.
¹³³ Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
¹³⁴ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA.
¹³⁵ Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA.
¹³⁶ Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA 19146, USA.
¹³⁷ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
¹³⁸ School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
¹³⁹ Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO 63108, USA; BioData Catalyst Program, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA.
¹⁴⁰ Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA; Framingham Heart Study, Boston University School of Medicine, Boston, MA 02118, USA.
¹⁴¹ The Charles R. Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mindich Child Health Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
¹⁴² Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Center for Diabetes Research, Wake Forest school of Medicine, Winston-Salem, NC 27157, USA.

PMID: 33713608
PMCID: PMC8059339
DOI: 10.1016/j.ajhg.2021.02.011

Abstract

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

Keywords: African ancestry; fine-mapping; genome-wide; height.

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Conflict of interest statement

The authors have nothing to declare.

Figures

**Figure 1**
Three-stage design to evaluate genetic association with height in sex-combined and sex-stratified samples In stage 1, genome-wide association results from 17 studies including 41,400 individuals (16,032 men and 25,368 women) of African ancestry (AA) were meta-analyzed. For variants with p

**Figure 2**
Locuszoom plots of six novel height loci *SLC4A3/MIR4268, NCOA2, ECD, RCCD1, G6PC3,* and *CEP95* in men and women combined (A) and *CRB1* and *KLF6/LINC00704* in women only (B). All plots use AFR LD from the 1000 Genomes phase 1 reference panel. In each plot, the most significant variant within a 1 Mb regional locus is highlighted. p values for all variants including the most significant variant are based on the African American discovery phase only (AA Stage1). In addition, for the most significant variant, p values are annotated and illustrated from the African American discovery and replication phases (AA Stage1+Stage2). For loci *SLC4A3/MIR4268, NCOA2, RCCD1, G6PC3,* and *CEP95*, the lead SNP are also shown for the European ancestry from the GIANT consortium effort combined with the African American discovery and replication phases (AA Stage1+Stage2 + EA).

**Figure 3**
Correlations (rho) between effect estimates and the loadings of the principal components 1–5 in each consortium GIANT (Genetic Investigation of ANthropometric Traits) and AAAGC (African American Anthropometry Genetics Consortium) and the meta-analysis of both (Meta).

See this image and copyright information in PMC

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References

1. Wood A.R., Esko T., Yang J., Vedantam S., Pers T.H., Gustafsson S., Chu A.Y., Estrada K., Luan J., Kutalik Z., Electronic Medical Records and Genomics (eMEMERGEGE) Consortium. MIGen Consortium. PAGEGE Consortium. LifeLines Cohort Study Defining the role of common variation in the genomic and biological architecture of adult human height. Nat. Genet. 2014;46:1173–1186. - PMC - PubMed
1. Weedon M.N., Lango H., Lindgren C.M., Wallace C., Evans D.M., Mangino M., Freathy R.M., Perry J.R., Stevens S., Hall A.S., Diabetes Genetics Initiative. Wellcome Trust Case Control Consortium. Cambridge GEM Consortium Genome-wide association analysis identifies 20 loci that influence adult height. Nat. Genet. 2008;40:575–583. - PMC - PubMed
1. Lango Allen H., Estrada K., Lettre G., Berndt S.I., Weedon M.N., Rivadeneira F., Willer C.J., Jackson A.U., Vedantam S., Raychaudhuri S. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010;467:832–838. - PMC - PubMed
1. Lettre G., Jackson A.U., Gieger C., Schumacher F.R., Berndt S.I., Sanna S., Eyheramendy S., Voight B.F., Butler J.L., Guiducci C., Diabetes Genetics Initiative. FUSION. KORA. Prostate, Lung Colorectal and Ovarian Cancer Screening Trial. Nurses’ Health Study. SardiNIA Identification of ten loci associated with height highlights new biological pathways in human growth. Nat. Genet. 2008;40:584–591. - PMC - PubMed
1. Yengo L., Sidorenko J., Kemper K.E., Zheng Z., Wood A.R., Weedon M.N., Frayling T.M., Hirschhorn J., Yang J., Visscher P.M., GIANT Consortium Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry. Hum. Mol. Genet. 2018;27:3641–3649. - PMC - PubMed

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[1] Wood A.R., Esko T., Yang J., Vedantam S., Pers T.H., Gustafsson S., Chu A.Y., Estrada K., Luan J., Kutalik Z., Electronic Medical Records and Genomics (eMEMERGEGE) Consortium. MIGen Consortium. PAGEGE Consortium. LifeLines Cohort Study Defining the role of common variation in the genomic and biological architecture of adult human height. Nat. Genet. 2014;46:1173–1186. - PMC - PubMed

[2] Wood A.R., Esko T., Yang J., Vedantam S., Pers T.H., Gustafsson S., Chu A.Y., Estrada K., Luan J., Kutalik Z., Electronic Medical Records and Genomics (eMEMERGEGE) Consortium. MIGen Consortium. PAGEGE Consortium. LifeLines Cohort Study Defining the role of common variation in the genomic and biological architecture of adult human height. Nat. Genet. 2014;46:1173–1186. - PMC - PubMed

[3] Weedon M.N., Lango H., Lindgren C.M., Wallace C., Evans D.M., Mangino M., Freathy R.M., Perry J.R., Stevens S., Hall A.S., Diabetes Genetics Initiative. Wellcome Trust Case Control Consortium. Cambridge GEM Consortium Genome-wide association analysis identifies 20 loci that influence adult height. Nat. Genet. 2008;40:575–583. - PMC - PubMed

[4] Weedon M.N., Lango H., Lindgren C.M., Wallace C., Evans D.M., Mangino M., Freathy R.M., Perry J.R., Stevens S., Hall A.S., Diabetes Genetics Initiative. Wellcome Trust Case Control Consortium. Cambridge GEM Consortium Genome-wide association analysis identifies 20 loci that influence adult height. Nat. Genet. 2008;40:575–583. - PMC - PubMed

[5] Lango Allen H., Estrada K., Lettre G., Berndt S.I., Weedon M.N., Rivadeneira F., Willer C.J., Jackson A.U., Vedantam S., Raychaudhuri S. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010;467:832–838. - PMC - PubMed

[6] Lango Allen H., Estrada K., Lettre G., Berndt S.I., Weedon M.N., Rivadeneira F., Willer C.J., Jackson A.U., Vedantam S., Raychaudhuri S. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010;467:832–838. - PMC - PubMed

[7] Lettre G., Jackson A.U., Gieger C., Schumacher F.R., Berndt S.I., Sanna S., Eyheramendy S., Voight B.F., Butler J.L., Guiducci C., Diabetes Genetics Initiative. FUSION. KORA. Prostate, Lung Colorectal and Ovarian Cancer Screening Trial. Nurses’ Health Study. SardiNIA Identification of ten loci associated with height highlights new biological pathways in human growth. Nat. Genet. 2008;40:584–591. - PMC - PubMed

[8] Lettre G., Jackson A.U., Gieger C., Schumacher F.R., Berndt S.I., Sanna S., Eyheramendy S., Voight B.F., Butler J.L., Guiducci C., Diabetes Genetics Initiative. FUSION. KORA. Prostate, Lung Colorectal and Ovarian Cancer Screening Trial. Nurses’ Health Study. SardiNIA Identification of ten loci associated with height highlights new biological pathways in human growth. Nat. Genet. 2008;40:584–591. - PMC - PubMed

[9] Yengo L., Sidorenko J., Kemper K.E., Zheng Z., Wood A.R., Weedon M.N., Frayling T.M., Hirschhorn J., Yang J., Visscher P.M., GIANT Consortium Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry. Hum. Mol. Genet. 2018;27:3641–3649. - PMC - PubMed

[10] Yengo L., Sidorenko J., Kemper K.E., Zheng Z., Wood A.R., Weedon M.N., Frayling T.M., Hirschhorn J., Yang J., Visscher P.M., GIANT Consortium Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry. Hum. Mol. Genet. 2018;27:3641–3649. - PMC - PubMed

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Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

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Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

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