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TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data.
- Source :
-
American journal of human genetics [Am J Hum Genet] 2022 Jun 02; Vol. 109 (6), pp. 1175-1181. Date of Electronic Publication: 2022 May 02. - Publication Year :
- 2022
-
Abstract
- 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.<br />Competing Interests: Declaration of interests L.M.R. is a consultant for the TOPMed Administrative Coordinating Center (through Westat).<br /> (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1537-6605
- Volume :
- 109
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 35504290
- Full Text :
- https://doi.org/10.1016/j.ajhg.2022.04.006