Evidence map›Paper›PMID 27346685›Full record

SynthesisAmerican journal of human genetics2016

Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits.

Nathalie Chami, Ming-Huei Chen, Andrew J Slater, John D Eicher, Evangelos Evangelou, Salman M Tajuddin, Latisha Love-Gregory, Tim Kacprowski, Ursula M Schick, Akihiro Nomura and 103 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 6 pooled it
6.8field-weighted citation impact, top 3% of its field
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

51 citing papers in PubMed, 6 syntheses or guidelines pooled it, 98 citations in OpenAlex.

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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

113 authors at 20 institutions in 13 countries.

Nathalie ChamiDepartment of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.
Ming-Huei ChenPopulation Sciences Branch, National Heart, Lung, and Blood Institute, The Framingham Heart Study, Framingham, MA 01702, USA.
Andrew J SlaterGenetics Target Sciences, GlaxoSmithKline, Research Triangle Park, NC 27709, USA; OmicSoft Corporation, Cary, NC 27513, USA.
John D EicherPopulation Sciences Branch, National Heart, Lung, and Blood Institute, The Framingham Heart Study, Framingham, MA 01702, USA.
Evangelos EvangelouDepartment of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina 45110, Greece.
Salman M TajuddinLaboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Latisha Love-GregoryDepartment of Medicine, Center of Human Nutrition, Washington University School of Medicine, St Louis, MO 63110, USA.
Tim KacprowskiDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine, Greifswald and Ernst-Mortiz-Arndt University Greifswald, Greifswald 17475, Germany; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald QA, Germany.
Ursula M SchickThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10069, USA.
Akihiro NomuraCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Cardiovascular Medicine, Kanazawa University, Graduate School of Medical Science, Kanazawa, Ishikawa 9200942, Japan.
Ayush GiriDivision of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN 37235, USA.
Samuel LessardDepartment of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.
Jennifer A BrodyDepartment of Medicine, University of Washington, Seattle, WA 98101, USA.
Claudia SchurmannThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10069, USA; The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10069, USA.
Nathan PankratzDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55454, USA.
Lisa R YanekDepartment of Medicine/Division of General Internal Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Ani ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
Raha PazokiDepartment of Epidemiology, Erasmus, MC Rotterdam 3000, the Netherlands.
Evelin MihailovEstonian Genome Center, University of Tartu, Tartu 51010, Estonia.
W David HillCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Laura M RaffieldDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27514, USA.
Amber BurtDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Traci M BartzDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Diane M BeckerDepartment of Medicine/Division of General Internal Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Lewis C BeckerDepartment of Medicine/Divisions of Cardiology and General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Eric BoerwinkleHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Jette Bork-JensenThe Novo Nordisk Foundation, Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
Erwin P BottingerThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10069, USA.
Michelle L O'DonoghueTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
David R CrosslinDepartment of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA 98195, USA.
Simon de DenusMontreal Heart Institute, Montréal, QC H1T 1C8, Canada; Faculty of Pharmacy, Université de Montréal, Montréal, QC H3T 1J4, Canada.
Marie-Pierre DubéDepartment of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.
Paul ElliottDepartment of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
Gunnar EngströmDepartment of Clinical Sciences, Malmö, Lund University, Malmö 221 00, Sweden; Skåne University Hospital, Malmö 222 41, Sweden.
Michele K EvansLaboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
James S FloydDepartment of Medicine, University of Washington, Seattle, WA 98101, USA.
Myriam FornageInstitute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
He GaoDepartment of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
Andreas GreinacherInstitute for Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
Vilmundur GudnasonIcelandic Heart Association, 201 Kopavogur, Iceland; Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
Torben HansenThe Novo Nordisk Foundation, Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
Tamara B HarrisLaboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Intramural Research Program, NIH, Bethesda, MD 20892, USA.
Caroline HaywardMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
Jussi HernesniemiDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland; University of Tampere, School of Medicine, Tampere 33014, Finland.
Heather M HighlandHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Joel N HirschhornProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Department of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
Albert HofmanDepartment of Epidemiology, Erasmus, MC Rotterdam 3000, the Netherlands; Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA 02115, USA.
Marguerite R IrvinDepartment of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Mika KähönenDepartment of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland; Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33014, Finland.
Ethan LangeDepartments of Genetics and Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Lenore J LaunerLaboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Intramural Research Program, NIH, Bethesda, MD 20892, USA.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland.
Jin LiDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University, School of Medicine, Palo Alto, CA 94305, USA.
David C M LiewaldCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Allan LinnebergResearch Centre for Prevention and Health, The Capital Region of Denmark, Copenhagen 2600, Denmark; Department of Clinical Experimental Research, Rigshospitalet, Glostrup 2100, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
Yongmei LiuCenter for Human Genetics, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Yingchang LuThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10069, USA; The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10069, USA.
Leo-Pekka LyytikäinenDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland.
Reedik MägiEstonian Genome Center, University of Tartu, Tartu 51010, Estonia.
Rasika A MathiasDepartment of Medicine, Divisions of Allergy and Clinical Immunology and General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Olle MelanderDepartment of Clinical Sciences, Malmö, Lund University, Malmö 221 00, Sweden; Skåne University Hospital, Malmö 222 41, Sweden.
Andres MetspaluEstonian Genome Center, University of Tartu, Tartu 51010, Estonia.
Nina MononenDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland.
Mike A NallsLaboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
Deborah A NickersonDepartment of Genome Sciences, University of Washington, Seattle, WA 98105, USA.
Kjell NikusUniversity of Tampere, School of Medicine, Tampere 33014, Finland; Department of Cardiology, Heart Center, Tampere University Hospital, Tampere 33521, Finland.
Chris J O'DonnellPopulation Sciences Branch, National Heart, Lung, and Blood Institute, The Framingham Heart Study, Framingham, MA 01702, USA; Cardiology Section and Center for Population Genomics, Boston Veteran's Administration (VA) Healthcare, Boston, MA 02118, USA.
Marju Orho-MelanderDepartment of Clinical Sciences, Malmö, Lund University, Malmö 221 00, Sweden; Skåne University Hospital, Malmö 222 41, Sweden.
Oluf PedersenThe Novo Nordisk Foundation, Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
Astrid PetersmannInstitute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
Linda PolfusHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine Epidemiology and Health Services, University of Washington, Seattle, WA 98101, USA; Group Health Research Institute, Group Health Cooperative, Seattle, WA 98101, USA.
Olli T RaitakariDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20521, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland.
Emma RaitoharjuDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland; Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland.
Melissa RichardInstitute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Kenneth M RiceDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Fernando RivadeneiraDepartment of Epidemiology, Erasmus, MC Rotterdam 3000, the Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam 3000, the Netherlands; Netherlands Consortium for Healthy Ageing (NCHA), Rotterdam 3015, the Netherlands.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Frank SchmidtDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine, Greifswald and Ernst-Mortiz-Arndt University Greifswald, Greifswald 17475, Germany.
Albert Vernon SmithIcelandic Heart Association, 201 Kopavogur, Iceland; Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
John M StarrCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Alzheimer Scotland Research Centre, Edinburgh EH8 9JZ, UK.
Kent D TaylorInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Alexander TeumerInstitute for Community Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
Betina H ThuesenResearch Centre for Prevention and Health, The Capital Region of Denmark, Copenhagen 2600, Denmark.
Eric S TorstensonDivision of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN 37235, USA.
Russell P TracyDepartments of Pathology and Laboratory Medicine and Biochemistry, University of Vermont College of Medicine, Colchester, VT 05446, USA.
Ioanna TzoulakiDepartment of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina 45110, Greece.
Neil A ZakaiDepartments of Medicine and Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Caterina Vacchi-SuzziDepartment of Family Population and Preventive Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus, MC Rotterdam 3000, the Netherlands.
Frank J A van RooijDepartment of Epidemiology, Erasmus, MC Rotterdam 3000, the Netherlands.
Mary CushmanDepartments of Medicine and Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK; Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
Digna R Velez EdwardsVanderbilt Epidemiology Center, Department of Obstetrics & Gynecology, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN 37203, USA.
Anne-Claire VergnaudDepartment of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
Lars WallentinDepartment of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala 751 85, Sweden.
Dawn M WaterworthGenetics Target Sciences, GlaxoSmithKline, King of Prussia, PA 19406, USA.
Harvey D WhiteGreen Lane Cardiovascular Service, Auckland City Hospital and University of Auckland, Auckland 1142, New Zealand.
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Alan B ZondermanLaboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Sekar KathiresanCenter for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Niels GrarupThe Novo Nordisk Foundation, Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
Tõnu EskoProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10069, USA; The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10069, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10069, USA.
Leslie A LangeDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27514, USA.
Nauder FaradayDepartment of Anesthesiology & Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Nada A AbumradDepartment of Medicine, Center of Human Nutrition, Washington University School of Medicine, St Louis, MO 63110, USA.
Todd L EdwardsDivision of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, TN 37235, USA.
Santhi K GaneshDepartments of Internal Medicine and Human Genetics, University of Michigan, Ann Arbor, MI 48108, USA.
Paul L AuerZilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53205, USA.
Andrew D JohnsonPopulation Sciences Branch, National Heart, Lung, and Blood Institute, The Framingham Heart Study, Framingham, MA 01702, USA.
Alexander P ReinerDepartment of Epidemiology, University of Washington, Seattle, WA 98195, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: apreiner@u.washington.edu.
Guillaume LettreDepartment of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; Montreal Heart Institute, Montréal, QC H1T 1C8, Canada. Electronic address: guillaume.lettre@umontreal.ca.
National Institute on Aging · USJohns Hopkins University · USUniversity of Washington · USErasmus MC · NLIcahn School of Medicine at Mount Sinai · USImperial College London · GBTampere University · FIThe University of Texas Health Science Center at Houston · USUniversity of Copenhagen · DKUniversity of Edinburgh · GBVanderbilt University · USLund University · SEMontreal Heart Institute · CANational Heart Lung and Blood Institute · USUniversitätsmedizin Greifswald · DEUniversity of North Carolina at Chapel Hill · USUniversity of Tartu · EEUniversity of Vermont · USBroad Institute · USHarbor–UCLA Medical Center · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4M
Washington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Dominic N Reeds · 1999 to 2026
$30.2M
Cardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3M
The Underlying Biology of Health DisparitiesZIAAG000519 · NIA · NATIONAL INSTITUTE ON AGING · PI EVANS, MICHELE K · 2009 to 2025
$15.7M
Cardiovascular Epidemiology Training GrantT32HL007055 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Wayne D. Rosamond · 1986 to 2026
$10.0M
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
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
CD36 AND INTESTINAL FAT ABSORPTIONR01DK060022 · NIDDK · WASHINGTON UNIVERSITY · PI ABUMRAD, NADA A. · 2001 to 2021
$7.7M
FATTY ACID TRANSPORTER: REGULATION, IDENTIFICATIONR01DK033301 · NIDDK · WASHINGTON UNIVERSITY · PI ABUMRAD, NADA A. · 1986 to 2017
$5.2M
A Family-based Exome Sequencing Approach to Identify Platelet Aggregation GenesR01HL112064 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MATHIAS, RASIKA ANN · 2012 to 2015
$5.1M
Genetic Studies of The Impact of Hematologic Traits On Cardiovascular DiseaseR01HL122684 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GANESH, SANTHI K · 2015 to 2019
$3.4M
Medical Research Council MC_PC_U127561128Medical Research Council MR/K026992/1NCATS NIH HHS UL1 TR000124NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL107816NHLBI NIH HHS R01 HL112064NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL122684NHLBI NIH HHS R21 HL121422NHLBI NIH HHS R21 HL121429NHLBI NIH HHS T32 HL007055NICHD NIH HHS R01 HD074711NIDDK NIH HHS P30 DK056341NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK033301NIDDK NIH HHS R01 DK060022NIH HHS S10 OD018522
6 · The paper itself

Abstract

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 × 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 × 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 × 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.

Indexed as

Genetic PleiotropyGenotypeAllelic ImbalanceBlack or African AmericanErythrocyte IndicesErythrocytesErythropoiesisExomeGene FrequencyGenetic VariationHematocritHemoglobinsHumansQuantitative Trait LociHemoglobins

Identifiers

PMID27346685
PMCPMC5005438
OpenAlexW2465575411

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.