Evidence map›Paper›PMID 34582791›Full record

ArticleAmerican journal of human genetics2021

Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: The NHLBI TOPMed program.

Anna V Mikhaylova, Caitlin P McHugh, Linda M Polfus, Laura M Raffield, Meher Preethi Boorgula, Thomas W Blackwell, Jennifer A Brody, Jai Broome, Nathalie Chami, Ming-Huei Chen and 84 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
2.4field-weighted citation impact, top 11% 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

18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Whole Blood Transcriptomic Analysis of Sickle Cell Trait.European journal of haematology · 2026
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  11. Building a collaborative cloud platform to accelerate heart, lung, blood, and sleep research.Journal of the American Medical Informatics Association : JAMIA · 2023
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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

94 authors at 20 institutions in 3 countries.

Anna V MikhaylovaDepartment of Biostatistics, University of Washington, Seattle, WA 98105, USA.
Caitlin P McHughDepartment of Biostatistics, University of Washington, Seattle, WA 98105, USA.
Linda M PolfusKeck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Meher Preethi BoorgulaDivision of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Thomas W BlackwellTOPMed Informatics Research Center, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98105, USA.
Jai BroomeDepartment of Biostatistics, University of Washington, Seattle, WA 98105, USA.
Nathalie ChamiThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.
Ming-Huei ChenPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA; National Heart, Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01701, USA.
Matthew P ConomosDepartment of Biostatistics, University of Washington, Seattle, WA 98105, USA.
Corey CoxDivision of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, 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 78539, USA.
Michelle DayaDivision of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Lynette EkunweDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
David C GlahnDepartment of Psychiatry, Boston Children's Hospital and Harvard Medical School, Boston, MA 02155, USA.
Nancy Heard-CostaNational Heart, Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01701, USA; Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.
Heather M HighlandDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Brian D HobbsChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Yann IlboudoMontréal Heart Institute, Montréal, Québec H1T 1C8, Canada; Faculté de Médecine, Université de Montréal, Montréal, Québec H1T 1C8, Canada.
Deepti JainDepartment of Biostatistics, University of Washington, Seattle, WA 98105, USA.
Leslie A LangeDivision of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Tyne W Miller-FlemingDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37240, USA.
Nancy MinDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Jee-Young MoonDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Michael H PreussThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.
Jonathon RosenDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Kathleen RyanDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Albert V SmithTOPMed Informatics Research Center, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
Quan SunDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Praveen SurendranBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge CB1 8RN, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge CB1 8RN, UK; Rutherford Fund Fellow, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, 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.
Klaudia WalterDepartment of Human Genetics, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Zhe WangThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.
Marsha WheelerDepartment of Genome Sciences, University of Washington, Seattle, WA 98105, USA.
Lisa R YanekDivision of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Xue ZhongDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37240, USA.
Goncalo R AbecasisTOPMed Informatics Research Center, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
Laura AlmasyDepartment of Biomedical and Health Informatics, the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Kathleen C BarnesDivision of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Terri H BeatySchool of Public Health, John Hopkins University, Baltimore, MD 21205, USA.
Lewis C BeckerDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
John BlangeroDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX 78539, 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.
Adam S ButterworthBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge CB1 8RN, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge CB1 8RN, UK; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge CB1 8RN, UK; National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge CB1 8RN, UK.
Sameer ChavanDivision of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Michael H ChoChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Hélène ChoquetDivision of Research, Kaiser Permanente Northern California, Oakland, CA 94601, USA.
Adolfo CorreaDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Nancy CoxDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37240, USA.
Dawn L DeMeoChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Nauder FaradayDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Myriam FornageUniversity of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Robert E GersztenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Lifang HouInstitute for Public Health and Medicine, Northwestern University, Chicago, IL 60661, USA.
Andrew D JohnsonPopulation Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA; National Heart, Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01701, USA.
Eric JorgensonRegeneron Genetics Center, Tarrytown, NY 10591, USA.
Robert KaplanDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Charles KooperbergPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Kousik KunduDepartment of Human Genetics, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK; Department of Haematology, University of Cambridge, Cambridge CB1 8RN, UK.
Cecelia A LaurieDepartment of Biostatistics, University of Washington, Seattle, WA 98105, USA.
Guillaume LettreMontréal Heart Institute, Montréal, Québec H1T 1C8, Canada; Faculté de Médecine, Université de Montréal, Montréal, Québec H1T 1C8, Canada.
Joshua P LewisDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Bingshan LiDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
Yun LiDepartments of Biostatistics, Genetics, and Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Donald M Lloyd-JonesDivision of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60661, USA; Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60661, USA.
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.
Ani ManichaikulCenter for Public Health Genomics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Deborah A MeyersDivision of Genetics, Genomics and Precision Medicine, Department of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Braxton D MitchellDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA.
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.
Debby NgoBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Deborah A NickersonDepartment of Genome Sciences, University of Washington, Seattle, WA 98105, USA.
Suraj NongmaithemDepartment of Human Genetics, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
Kari E NorthDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jeffrey R O'ConnellDepartment of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Victor E OrtegaDepartment of Internal Medicine, Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
Nathan PankratzDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
James A PerryDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Bruce M PsatyDepartment of Epidemiology, University of Washington, Seattle, WA 98105, USA; Department of Health Service, University of Washington, Seattle, WA 98105, USA; Department of Medicine, University of Washington, Seattle, WA 98105, USA.
Stephen S RichCenter for Public Health Genomics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Nicole SoranzoDepartment of Human Genetics, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge CB1 8RN, UK; Department of Haematology, University of Cambridge, Cambridge CB1 8RN, UK; British Heart Foundation Centre of Excellence, Division of Cardiovascular Medicine, Addenbrooke's Hospital, Cambridge CB1 8RN, UK.
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.
Edwin K SilvermanChanning Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Nicholas L SmithDepartment of Epidemiology, University of Washington, Seattle, WA 98105, USA; Department of Health Service, University of Washington, Seattle, WA 98105, USA; Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA 98105, USA.
Hua TangDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Russell P TracyDepartment of Pathology and Laboratory Medicine and Department of Biochemistry, University of Vermont Larner College of Medicine, Colchester, VT 05446, USA.
Timothy A ThorntonDepartment of Biostatistics, University of Washington, Seattle, WA 98105, USA; Regeneron Genetics Center, Tarrytown, NY 10591, USA.
Ramachandran S VasanNational Heart, Lung and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA 01701, USA; Departments of Cardiology and Preventive Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA.
Joe ZeinRespiratory Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Rasika A MathiasDivision of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Alexander P ReinerDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: apreiner@uw.edu.
Paul L AuerZilber School of Public Health, University of Wisconsin, Milwaukee, Milwaukee, WI 53205, USA. Electronic address: pauer@mcw.edu.
University of Washington · USUniversity of Colorado Anschutz Medical Campus · USUniversity of North Carolina at Chapel Hill · USUniversity of Maryland, Baltimore · USBrigham and Women's Hospital · USIcahn School of Medicine at Mount Sinai · USThe University of Texas Health Science Center at Houston · USJohns Hopkins University · USUniversity of Michigan–Ann Arbor · USUniversity of Mississippi Medical Center · USVanderbilt University Medical Center · USWellcome Sanger Institute · GBAlbert Einstein College of Medicine · USFramingham Heart Study · USJohns Hopkins Medicine · USMontreal Heart Institute · CANorthwestern University · USThe University of Texas Rio Grande Valley · USUniversity of Cambridge · GBUniversity of Virginia · US

Funding

North Carolina Translational and Clinical Science Institute (NC TraCS) KL2KL2TR002490 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WEINBERGER, MORRIS · 2018 to 2022
$11.0M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
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
Next generation functional genomics of hematology traitsR01HL146500 · NHLBI · UNIVERSITY OF WASHINGTON · PI ALEXANDER P REINER · 2020 to 2026
$5.7M
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
The Genetic Epidemiology of Heart, Lung, and Blood TraitsTraining Grant (GenHLB)T32HL129982 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Christy Leigh Avery, KAREN L. MOHLKE · 2016 to 2026
$3.8M
Multi-omic studies of asthma severity in an African ancestry populationR01AI132476 · NIAID · UNIVERSITY OF COLORADO DENVER · PI BARNES, KATHLEEN C, MATHIAS, RASIKA ANN · 2018 to 2022
$3.5M
Sequence analysis of hemotological traits in African AmericansR01HL130733 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LANGE, ETHAN MATHER, REINER, ALEXANDER P · 2016 to 2019
$2.7M
Genetic Studies of Blood Cell Traits in Multi-Ethnic CohortsR01HL129132 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LI, YUN, REINER, ALEXANDER P · 2016 to 2019
$2.7M
From gene regions to whole chromosomes: scaling up association-finding for disease and omics outcomes in TOPMedU01HL137162 · NHLBI · UNIVERSITY OF WASHINGTON · PI RICE, KENNETH M. · 2017 to 2019
$1.6M
Multi-omic Subtyping of Chronic Obstructive Pulmonary DiseaseK08HL136928 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI HOBBS, BRIAN DANIEL · 2017 to 2021
$864k
NCATS NIH HHS KL2 TR002490NHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS K08 HL136928NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL129132NHLBI NIH HHS R01 HL130733NHLBI NIH HHS R01 HL146500NHLBI NIH HHS T32 HL129982NHLBI NIH HHS U01 HL120393NHLBI NIH HHS U01 HL137162NIAID NIH HHS R01 AI132476
6 · The paper itself

Abstract

Many common and rare variants associated with hematologic traits have been discovered through imputation on large-scale reference panels. However, the majority of genome-wide association studies (GWASs) have been conducted in Europeans, and determining causal variants has proved challenging. We performed a GWAS of total leukocyte, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts generated from 109,563,748 variants in the autosomes and the X chromosome in the Trans-Omics for Precision Medicine (TOPMed) program, which included data from 61,802 individuals of diverse ancestry. We discovered and replicated 7 leukocyte trait associations, including (1) the association between a chromosome X, pseudo-autosomal region (PAR), noncoding variant located between cytokine receptor genes (CSF2RA and CLRF2) and lower eosinophil count; and (2) associations between single variants found predominantly among African Americans at the S1PR3 (9q22.1) and HBB (11p15.4) loci and monocyte and lymphocyte counts, respectively. We further provide evidence indicating that the newly discovered eosinophil-lowering chromosome X PAR variant might be associated with reduced susceptibility to common allergic diseases such as atopic dermatitis and asthma. Additionally, we found a burden of very rare FLT3 (13q12.2) variants associated with monocyte counts. Together, these results emphasize the utility of whole-genome sequencing in diverse samples in identifying associations missed by European-ancestry-driven GWASs.

Indexed as

Polymorphism, Single NucleotideQuantitative Trait LociAsthmaBiomarkersDermatitis, AtopicGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHumansLeukocytesNational Heart, Lung, and Blood Institute (U.S.)PhenotypePrognosisProteomePulmonary Disease, Chronic ObstructiveUnited KingdomBiomarkersProteomeblood-cell countswhole-genome sequencing

Identifiers

PMID34582791
PMCPMC8546043
OpenAlexW3204654990

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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.