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

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 wi...

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Podrobná bibliografie
Vydáno v:	American journal of human genetics Ročník 109; číslo 6; s. 1175
Hlavní autoři:	Huang, Le, Rosen, Jonathan D, Sun, Quan, Chen, Jiawen, Wheeler, Marsha M, Zhou, Ying, Min, Yuan-I, Kooperberg, Charles, Conomos, Matthew P, Stilp, Adrienne M, Rich, Stephen S, Rotter, Jerome I, Manichaikul, Ani, Loos, Ruth J F, Kenny, Eimear E, Blackwell, Thomas W, Smith, Albert V, Jun, Goo, Sedlazeck, Fritz J, Metcalf, Ginger, Boerwinkle, Eric, Raffield, Laura M, Reiner, Alex P, Auer, Paul L, Li, Yun
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 02.06.2022
Témata:	Asian People Genome-Wide Association Study Humans Linkage Disequilibrium - genetics Polymorphism, Single Nucleotide - genetics Precision Medicine Whole Genome Sequencing
ISSN:	1537-6605, 1537-6605
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1537-6605 1537-6605
DOI:	10.1016/j.ajhg.2022.04.006