TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data
In: American Journal of Human Genetics, Jg. 109 (2022-06-01), Heft 6
Online
academicJournal
- 1175 - 1181
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.
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TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data
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Autor/in / Beteiligte Person: | 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 JF ; Kenny, Eimear E ; Blackwell, Thomas W ; Smith, Albert V ; Jun, Goo ; Sedlazeck, Fritz J ; Metcalf, Ginger ; Boerwinkle, Eric ; Consortium, NHLBI Trans-Omics for Precision Medicine ; Raffield, Laura M ; Reiner, Alex P ; Auer, Paul L ; Li, Yun |
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Zeitschrift: | American Journal of Human Genetics, Jg. 109 (2022-06-01), Heft 6 |
Veröffentlichung: | eScholarship, University of California, 2022 |
Medientyp: | academicJournal |
Umfang: | 1175 - 1181 |
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