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 - Funding Information:
We gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed. The TOPMed Banner Authorship list can be found at: https://www.nhlbiwgs.org/topmed-banner-authorship . The project described is supported by funding from the National Institutes of Health through R01HL129132 and U01HG011720 (Y.L.), R01HL146500 (A.P.R.), and KL2TR002490 (L.M.R.). Y.L., J.D.R., and L.H. are also partially supported by R01HL146500 , U24 AR076730 , and U01DA052713 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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
VL - 109
SP - 1175
EP - 1181
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 6
ER -