TY - JOUR
T1 - TOP-LD
T2 - A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data
AU - NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
AU - Huang, Le
AU - Rosen, Jonathan D.
AU - Sun, Quan
AU - Chen, Jiawen
AU - Wheeler, Marsha M.
AU - Zhou, Ying
AU - Min, Yuan I.
AU - Kooperberg, Charles
AU - Conomos, Matthew P.
AU - Stilp, Adrienne M.
AU - Rich, Stephen S.
AU - Rotter, Jerome I.
AU - Manichaikul, Ani
AU - Loos, Ruth J.F.
AU - Kenny, Eimear E.
AU - Blackwell, Thomas W.
AU - Smith, Albert V.
AU - Jun, Goo
AU - Sedlazeck, Fritz J.
AU - Metcalf, Ginger
AU - Boerwinkle, Eric
AU - Raffield, Laura M.
AU - Reiner, Alex P.
AU - Auer, Paul L.
AU - Li, Yun
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/6/2
Y1 - 2022/6/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85131100015&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2022.04.006
DO - 10.1016/j.ajhg.2022.04.006
M3 - Article
C2 - 35504290
AN - SCOPUS:85131100015
SN - 0002-9297
VL - 109
SP - 1175
EP - 1181
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -