| Title: | TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data |
| Journal: | American Journal of Human Genetics |
| Published: | 2 May 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35504290/ |
| DOI: | https://doi.org/10.1016/j.ajhg.2022.04.006 |
| URL: | http://www.cell.com/article/S0002929722001549/pdf |
Publication 10228
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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.</p>
26 Authors
- Le Huang
- Jonathan D. Rosen
- Quan Sun
- Jiawen Chen
- Marsha M. Wheeler
- Ying Zhou
- Yuan-I Min
- Charles Kooperberg
- Matthew P. Conomos
- Adrienne M. Stilp
- Stephen S. Rich
- Jerome I. Rotter
- Ani Manichaikul
- Ruth J.F. Loos
- Eimear E. Kenny
- Thomas W. Blackwell
- Albert V. Smith
- Goo Jun
- Fritz J. Sedlazeck
- Ginger Metcalf
- Eric Boerwinkle
- NHLBI Trans-Omics for Precision Medicine Consortium
- Laura M. Raffield
- Alex P. Reiner
- Paul L. Auer
- Yun Li
Enabling scientific discoveries that improve human health