TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data.

Asian People Genome-Wide Association Study Humans Linkage Disequilibrium / genetics Polymorphism, Single Nucleotide / genetics Precision Medicine Whole Genome Sequencing

Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
02 06 2022
Historique:
received: 20 12 2021
accepted: 08 04 2022
pubmed: 4 5 2022
medline: 9 6 2022
entrez: 3 5 2022
Statut: ppublish

Résumé

Current publicly available tools that allow rapid exploration of linkage disequilibrium (LD) between markers (e.g., HaploReg and LDlink) are based on whole-genome sequence (WGS) data from 2,504 individuals in the 1000 Genomes Project. Here, we present TOP-LD, an online tool to explore LD inferred with high-coverage (∼30×) WGS data from 15,578 individuals in the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. TOP-LD provides a significant upgrade compared to current LD tools, as the TOPMed WGS data provide a more comprehensive representation of genetic variation than the 1000 Genomes data, particularly for rare variants and in the specific populations that we analyzed. For example, TOP-LD encompasses LD information for 150.3, 62.2, and 36.7 million variants for European, African, and East Asian ancestral samples, respectively, offering 2.6- to 9.1-fold increase in variant coverage compared to HaploReg 4.0 or LDlink. In addition, TOP-LD includes tens of thousands of structural variants (SVs). We demonstrate the value of TOP-LD in fine-mapping at the GGT1 locus associated with gamma glutamyltransferase in the African ancestry participants in UK Biobank. Beyond fine-mapping, TOP-LD can facilitate a wide range of applications that are based on summary statistics and estimates of LD. TOP-LD is freely available online.

Identifiants

DOI: 10.1016/j.ajhg.2022.04.006 PMID: 35504290 PMC: PMC9247832
pubmed: 35504290
pii: S0002-9297(22)00154-9
doi: 10.1016/j.ajhg.2022.04.006
pmc: PMC9247832
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1175-1181

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL129132
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL129982
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA052713
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : U01 HG011720
Pays : United States
Organisme : NIAMS NIH HHS
ID : U24 AR076730
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL146500
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR002490
Pays : United States

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests L.M.R. is a consultant for the TOPMed Administrative Coordinating Center (through Westat).

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Auteurs

Le Huang (L)

Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Jonathan D Rosen (JD)

Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Quan Sun (Q)

Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Jiawen Chen (J)

Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Marsha M Wheeler (MM)

Department of Genome Sciences, University of Washington, Seattle, WA 98105, USA.

Ying Zhou (Y)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Yuan-I Min (YI)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.

Charles Kooperberg (C)

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Matthew P Conomos (MP)

Department of Biostatistics, University of Washington, Seattle, WA 98105, USA.

Adrienne M Stilp (AM)

Department of Biostatistics, University of Washington, Seattle, WA 98105, USA.

Stephen S Rich (SS)

Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

Jerome I Rotter (JI)

The 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.

Ani Manichaikul (A)

Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

Ruth J F Loos (RJF)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.

Eimear E Kenny (EE)

The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.

Thomas W Blackwell (TW)

TOPMed Informatics Research Center, University of Michigan, Department of Biostatistics, Ann Arbor, MI 48109, USA.

Albert V Smith (AV)

TOPMed Informatics Research Center, University of Michigan, Department of Biostatistics, Ann Arbor, MI 48109, USA.

Goo Jun (G)

Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Fritz J Sedlazeck (FJ)

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

Ginger Metcalf (G)

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.

Eric Boerwinkle (E)

Human 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.

Laura M Raffield (LM)

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Alex P Reiner (AP)

Department of Epidemiology, University of Washington, Seattle, WA 98195, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Paul L Auer (PL)

Division of Biostatistics, Institute for Health and Equity, and Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: pauer@mcw.edu.

Yun Li (Y)

Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, 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. Electronic address: yunli@med.unc.edu.

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Classifications MeSH

questionsmedicales.fr › Personnes › Asiatiques › TOP-LD: A tool to explore linkage...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › TOP-LD: A tool to explore linkage...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › TOP-LD: A tool to explore linkage...
questionsmedicales.fr › Phénomènes génétiques › Liaison génétique › Déséquilibre de liaison › TOP-LD: A tool to explore linkage...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Polymorphisme de nucléotide simple › TOP-LD: A tool to explore linkage...
questionsmedicales.fr › Professions de santé › Médecine › Médecine clinique › Médecine de précision › TOP-LD: A tool to explore linkage...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › TOP-LD: A tool to explore linkage...