Evidence map›Paper›PMID 34932938›Full record

ArticleAmerican journal of human genetics2022

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

George Hindy, Peter Dornbos, Mark D Chaffin, Dajiang J Liu, Minxian Wang, Margaret Sunitha Selvaraj, David Zhang, Joseph Park, Carlos A Aguilar-Salinas, Lucinda Antonacci-Fulton and 176 more

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In one paragraph

Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

186 authors.

George HindyProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Population Medicine, Qatar University College of Medicine, QU Health, Doha, Qatar.
Peter DornbosPrograms in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA.
Mark D ChaffinProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Dajiang J LiuDepartment of Public Health Sciences, Penn State College of Medicine, Hershey, PA 17033, USA.
Minxian WangProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Margaret Sunitha SelvarajProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
David ZhangDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Joseph ParkDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Carlos A Aguilar-SalinasInstituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico.
Lucinda Antonacci-FultonDepartment of Genetics, Washington University in St. Louis, St. Louis, MO 63110, USA; The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA.
Diego ArdissinoASTC: Associazione per lo Studio Della Trombosi in Cardiologia, Pavia, Italy; Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Universitˆ, degli Studi di Parma, Parma, Italy.
Donna K ArnettDean's Office, College of Public Health, University of Kentucky, Lexington, KY 40536, USA.
Stella AslibekyanDepartment of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Gil AtzmonDepartments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; University of Haifa, Faculty of Natural Science, Haifa, Israel.
Christie M BallantyneHouston Methodist Debakey Heart and Vascular Center, Houston, TX 77030, USA; Section of Cardiovascular Research, Baylor College of Medicine, Houston, TX 77030, USA.
Francisco Barajas-OlmosInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Nir BarzilaiDepartments of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Lewis C BeckerDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Lawrence F BielakDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 49109, USA.
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
John BlangeroDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.
Eric BoerwinkleHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Lori L BonnycastleMedical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Erwin BottingerHasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Digital Health Center, Hasso Plattner Institute, University of Potsdam, Potsdam, Germany.
Donald W BowdenDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Matthew J BownDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
Jai G BroomeDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Noël P BurttPrograms in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA 02142, USA.
Brian E CadeDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
Federico Centeno-CruzInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Edmund ChanDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
Yi-Cheng ChangInstitute of Biomedical Sciences, Academia Sinica, Taiwan.
Yii-Der I ChenThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Ching-Yu ChengDepartment of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
Won Jung ChoiPsomagen, Inc. (formerly Macrogen USA), 1330 Piccard Drive Ste 103, Rockville, MD 20850, USA.
Rajiv ChowdhuryMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Centre for Non-Communicable Disease Research, Bangladesh.
Cecilia Contreras-CubasInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Emilio J CórdovaInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Adolfo CorreaDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
L Adrienne CupplesDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA; NHLBI Framingham Heart Study, Framingham, MA 01702, USA.
Joanne E CurranDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.
John DaneshMRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; The National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics at the University of Cambridge, Cambridge, UK.
Paul S de VriesHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Ralph A DeFronzoDepartment of Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Harsha DoddapaneniHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Ravindranath DuggiralaDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.
Susan K DutcherDepartment of Genetics, Washington University in St. Louis, St. Louis, MO 63110, USA; The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA.
Patrick T EllinorCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Leslie S EmeryDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Jose C FlorezProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Diabetes Research Center (Diabetes Unit), Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Myriam FornageInstitute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 770030, USA.
Barry I FreedmanDepartment of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Valentin FusterDepartment of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Ma Eugenia Garay-SevillaDepartment of Medical Science, Division of Health Science, University of Guanajuato, Guanajuanto, Mexico.
Humberto García-OrtizInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Soren GermerNew York Genome Center, New York, NY 10013, USA.
Richard A GibbsHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Christian GiegerResearch Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research, Neuherberg, Germany.
Benjamin GlaserEndocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Clicerio GonzalezUnidad de Diabetes y Riesgo Cardiovascular, Instituto Nacional de Salud Pœblica, Cuernavaca, Morelos, Mexico.
Maria Elena Gonzalez-VillalpandoCentro de Estudios en Diabetes, Mexico City, Mexico.
Mariaelisa GraffDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Sarah E GrahamDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Niels GrarupNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Leif C GroopDepartment of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden; Finnish Institute for Molecular Genetics, University of Helsinki, Helsinki, Finland.
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Namrata GuptaProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Sohee HanDivision of Genome Science, Department of Precision Medicine, Chungcheongbuk-do, Republic of Korea.
Craig L HanisHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Jiang HeDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA; Tulane University Translational Science Institute, New Orleans, LA 70112, USA.
Nancy L Heard-CostaNHLBI Framingham Heart Study, Framingham, MA 01702, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
Yi-Jen HungDivision of Endocrine and Metabolism, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan.
Mi Yeong HwangDivision of Genome Science, Department of Precision Medicine, Chungcheongbuk-do, Republic of Korea.
Marguerite R IrvinDepartment of Epidemiology, School of Public Health, UAB, Birmingham, AL 35294, USA.
Sergio Islas-AndradeDirección de Investigación, Hospital General de México "Dr. Eduardo Liceaga," Secretaría de Salud, Mexico City, Mexico.
Gail P JarvikDepartments of Medicine (Medical Genetics) and Genome Sciences, University of Washington Medical Center, Seattle, WA 98195, USA.
Hyun Min KangDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Sharon L R KardiaDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 49109, USA.
Tanika KellyDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA.
Eimear E KennyDepartment of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Alyna T KhanDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Bong-Jo KimDivision of Genome Science, Department of Precision Medicine, Chungcheongbuk-do, Republic of Korea.
Ryan W KimPsomagen, Inc. (formerly Macrogen USA), 1330 Piccard Drive Ste 103, Rockville, MD 20850, USA.
Young Jin KimDivision of Genome Science, Department of Precision Medicine, Chungcheongbuk-do, Republic of Korea.
Heikki A KoistinenDepartment of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland; University of Helsinki and Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98103, USA.
Johanna KuusistoInstitute of Clinical Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
Soo Heon KwakDepartment of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Markku LaaksoInstitute of Clinical Medicine, University of Eastern Finland, and Kuopio University Hospital, Kuopio, Finland.
Leslie A LangeDepartment of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
Jiwon LeeDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Juyoung LeeDivision of Genome Science, Department of Precision Medicine, Chungcheongbuk-do, Republic of Korea.
Seonwook LeePsomagen, Inc. (formerly Macrogen USA), 1330 Piccard Drive Ste 103, Rockville, MD 20850, USA.
Donna M LehmanDepartment of Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA.
Rozenn N LemaitreCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
Allan LinnebergCenter for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jianjun LiuDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
Ruth J F LoosCharles R. Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Steven A LubitzCardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Valeriya LyssenkoDepartment of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden; University of Bergen, Bergen, Norway.
Ronald C W MaDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Lisa Warsinger MartinDivision of Cardiology, Department of Medicine, George Washington University, Washington, DC 20037, USA.
Angélica Martínez-HernándezInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Rasika A MathiasDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Stephen T McGarveyDepartment of Epidemiology and International Health Institute, Brown University School of Public Health, Providence, RI 02912, USA.
Ruth McPhersonRuddy Canadian Cardiovascuar Genetics Centre, University of Ottawa Heart Institute, Ottawa, ON, Canada.
James B MeigsDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; General Medicine Division, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Thomas MeitingerDeutsches Forschungszentrum fŸr Herz-Kreislauferkrankungen, Partner Site Munich Heart Alliance, Munich, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany.
Olle MelanderDepartment of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden; Department of Emergency and Internal Medicine, SkŒne University Hospital, Malmö, Sweden.
Elvia Mendoza-CaamalInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Ginger A MetcalfHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Xuenan MiDepartment of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA.
Karen L MohlkeDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27514, USA.
May E MontasserUniversity of Maryland School of Medicine, Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, Baltimore, MD 21201, USA.
Jee-Young MoonDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Hortensia Moreno-MacíasUniversidad Autónoma Metropolitana, Mexico City, Mexico.
Alanna C MorrisonHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Donna M MuznyHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Sarah C NelsonDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Peter M NilssonDepartment of Clinical Sciences, Lund University, Malmö, Sweden.
Jeffrey R O'ConnellUniversity of Maryland School of Medicine, Division of Endocrinology, Diabetes and Nutrition and Program for Personalized and Genomic Medicine, Baltimore, MD 21201, USA.
Marju Orho-MelanderDepartment of Clinical Sciences, Lund University, Malmö, Sweden.
Lorena OrozcoInstituto Nacional de Medicina Genómica, Mexico City, Mexico.
Colin N A PalmerPat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, Division of Population Health and Genomics, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Nicholette D PalmerDepartment of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Cheol Joo ParkPsomagen, Inc. (formerly Macrogen USA), 1330 Piccard Drive Ste 103, Rockville, MD 20850, USA.
Kyong Soo ParkDepartment of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
Oluf PedersenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Juan M PeraltaDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78520, USA.
Patricia A PeyserDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 49109, USA.
Wendy S PostDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
Michael PreussCharles R. Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA; Department of Epidemiology, University of Washington, Seattle, WA 98101, USA; Department of Health Services, University of Washington, Seattle, WA 98101, USA.
Qibin QiDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
D C RaoDivision of Biostatistics, Washington University School of Medicine, St. Louis, MO 63108, USA.
Susan RedlineDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
Alexander P ReinerUniversity of Washington, Seattle, WA 98101, USA.
Cristina Revilla-MonsalveInstituto Mexicano del Seguro Social SXXI, Mexico City, Mexico.
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
Nilesh SamaniDepartment of Cardiovascular Sciences, University of Leicester, Leicester, UK; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Heribert SchunkertDeutsches Herzzentrum München, Technische UniversitŠt München, Deutsches Zentrum fŸr Herz-Kreislauf-Forschung, München, Germany.
Claudia SchurmannHasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Digital Health Center, Hasso Plattner Institute, University of Potsdam, Potsdam, Germany; Charles R. Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Daekwan SeoPsomagen, Inc. (formerly Macrogen USA), 1330 Piccard Drive Ste 103, Rockville, MD 20850, USA.
Jeong-Sun SeoPsomagen, Inc. (formerly Macrogen USA), 1330 Piccard Drive Ste 103, Rockville, MD 20850, USA.
Xueling SimSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Rob SladekDepartment of Human Genetics, McGill University, Montreal, QC, Canada; Division of Endocrinology and Metabolism, Department of Medicine, McGill University, Montreal, QC, Canada; McGill University and Génome Québec Innovation Centre, Montreal, QC, Canada.
Kerrin S SmallDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Wing Yee SoDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Adrienne M StilpDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
E Shyong TaiDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Duke-NUS Medical School Singapore, Singapore.
Claudia H T TamDepartment of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Yik Ying TeoSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Department of Statistics and Applied Probability, National University of Singapore, Singapore; Life Sciences Institute, National University of Singapore, Singapore.
Farook ThameemDepartment of Biochemistry, Faculty of Medicine, Health Science Center, Kuwait University, Safat, Kuwait.
Brian TomlinsonFaculty of Medicine, Macau University of Science & Technology, Macau, China.
Michael Y TsaiDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Tiinamaija TuomiDepartment of Endocrinology, Abdominal Centre, Helsinki University Hospital, Helsinki, Finland; Folkhälsan Research Centre, Helsinki, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
Jaakko TuomilehtoPublic Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland; Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
Teresa Tusié-LunaInstituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico; Departamento de Medicina Genómica y Toxicología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México/ Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Miriam S UdlerProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Diabetes Research Center (Diabetes Unit), Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Rob M van DamSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore; Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Ramachandran S VasanNHLBI Framingham Heart Study, Framingham, MA 01702, USA; Departments of Medicine & Epidemiology, Boston University Schools of Medicine & Public Health, Boston, MA 02118, USA.
Karine A Viaud MartinezIllumina Laboratory Services, Illumina Inc., San Diego, CA 92122, USA.
Fei Fei WangDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Xuzhi WangDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
Hugh WatkinsCardiovascular Medicine, Radcliffe Department of Medicine and the Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Daniel E WeeksDepartment of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
James G WilsonDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Daniel R WitteDepartment of Public Health, Aarhus University, Aarhus, Denmark; Steno Diabetes Center Aarhus, Aarhus, Denmark.
Tien-Yin WongDepartment of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
Lisa R YanekDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
AMP-T2D-GENES, Myocardial Infarction Genetics Consortium
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
NHLBI TOPMed Lipids Working Group
Sekar KathiresanProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Verve Therapeutics, Cambridge, MA 02139, USA.
Daniel J RaderDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Michael BoehnkeDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Mark I McCarthyOxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Cristen J WillerDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Pradeep NatarajanProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Jason A FlannickPrograms in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA.
Amit V KheraProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Gina M PelosoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA. Electronic address: gpeloso@bu.edu.

Funding

PEDIGREE ANALYSIS OF LIPOPROTEIN PHENOTYPESP01HL045522 · NHLBI · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI BLANGERO, JOHN · 1991 to 2012
$27.6M
Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
University of Alabama at Birmingham's Diabetes Research CenterP30DK079626 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Kirk Michael Habegger · 2013 to 2026
$19.5M
Identifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6M
Targeted Genetic Analysis of T2D and Quantitative TraitsR01DK072193 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2005 to 2026
$11.3M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Using genetics to discover mechanisms of myocardial infarctionR01HL109946 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YUQING Eugene CHEN, Ida Liisa Surakka · 2011 to 2026
$8.9M
Whole Genome Sequencing to Identify Causal Genetic Variants Influencing CVD RiskR01HL113323 · NHLBI · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · PI BLANGERO, JOHN, CURRAN, JOANNE E. · 2012 to 2016
$8.2M
Genetic epidemiology of rare and regulatory variants for metabolic traitsR01DK093757 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAREN L. MOHLKE · 2011 to 2026
$8.2M
Using genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3M
Phenotypic and Molecular Signatures for Sleep Apnea and Related MorbiditiesR35HL135818 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI REDLINE, SUSAN S. · 2017 to 2023
$7.2M
Identifying Genes for Type 2 Diabetes:FUSIONR01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2003 to 2025
$6.7M
British Heart Foundation CH/12/2/29428British Heart Foundation CS/14/2/30841British Heart Foundation RG/13/13/30194British Heart Foundation RG/18/10/33842British Heart Foundation RG/18/13/33946NHGRI NIH HHS K08 HG010155NHLBI NIH HHS K01 HL135405NHLBI NIH HHS P01 HL045522NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL109946NHLBI NIH HHS R01 HL113323NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R01 HL142711NHLBI NIH HHS R01 HL153805NHLBI NIH HHS R03 HL154284NHLBI NIH HHS R35 HL135818NIA NIH HHS R01 AG058921NIDDK NIH HHS K23 DK114551NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK079626NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R01 DK072193NIDDK NIH HHS R01 DK093757NIDDK NIH HHS R01 DK125490NIDDK NIH HHS R01 DK127636NIDDK NIH HHS R03 DK131249NIDDK NIH HHS U01 DK062370NIDDK NIH HHS UM1 DK078616
6 · The paper itself

Abstract

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, SH2B3, and PLIN1) had no prior association of rare coding variants with lipid levels. Most of our associated genes showed evidence of association among multiple ancestries. Finally, we observed an enrichment of gene-based associations for low-density lipoprotein cholesterol drug target genes and for genes closest to GWAS index single-nucleotide polymorphisms (SNPs). Our results demonstrate that gene-based associations can be beneficial for drug target development and provide evidence that the gene closest to the array-based GWAS index SNP is often the functional gene for blood lipid levels.

Indexed as

ExomeGenetic VariationGenome-Wide Association StudyOpen Reading FramesAllelesBlood GlucoseCase-Control StudiesComputational BiologyDatabases, GeneticDiabetes Mellitus, Type 2Genetic Predisposition to DiseaseGenetics, PopulationHumansLipid MetabolismLipidsLiverBlood GlucoseLipidsassociationcholesterolexome sequencinggene-based associationlipid

Identifiers

PMID34932938
PMCPMC8764201

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