학술논문
TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data
Document Type
article
Author
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
Source
American Journal of Human Genetics. 109(6)
Subject
Language
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.