TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data
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 wi...
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| Vydáno v: | American journal of human genetics Ročník 109; číslo 6; s. 1175 |
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United States
02.06.2022
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| ISSN: | 1537-6605, 1537-6605 |
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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. |
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| AbstractList | 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. 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.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. |
| Author | Huang, Le Rich, Stephen S Min, Yuan-I Wheeler, Marsha M Raffield, Laura M Li, Yun Sedlazeck, Fritz J Rotter, Jerome I Loos, Ruth J F Boerwinkle, Eric Rosen, Jonathan D Sun, Quan Stilp, Adrienne M Chen, Jiawen Reiner, Alex P Blackwell, Thomas W Metcalf, Ginger Kenny, Eimear E Auer, Paul L Kooperberg, Charles Smith, Albert V Zhou, Ying Manichaikul, Ani Jun, Goo Conomos, Matthew P |
| Author_xml | – sequence: 1 givenname: Le surname: Huang fullname: Huang, Le organization: Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 2 givenname: Jonathan D surname: Rosen fullname: Rosen, Jonathan D organization: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 3 givenname: Quan surname: Sun fullname: Sun, Quan organization: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 4 givenname: Jiawen surname: Chen fullname: Chen, Jiawen organization: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 5 givenname: Marsha M surname: Wheeler fullname: Wheeler, Marsha M organization: Department of Genome Sciences, University of Washington, Seattle, WA 98105, USA – sequence: 6 givenname: Ying surname: Zhou fullname: Zhou, Ying organization: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA – sequence: 7 givenname: Yuan-I surname: Min fullname: Min, Yuan-I organization: Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA – sequence: 8 givenname: Charles surname: Kooperberg fullname: Kooperberg, Charles organization: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA – sequence: 9 givenname: Matthew P surname: Conomos fullname: Conomos, Matthew P organization: Department of Biostatistics, University of Washington, Seattle, WA 98105, USA – sequence: 10 givenname: Adrienne M surname: Stilp fullname: Stilp, Adrienne M organization: Department of Biostatistics, University of Washington, Seattle, WA 98105, USA – sequence: 11 givenname: Stephen S surname: Rich fullname: Rich, Stephen S organization: Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA 22908, USA – sequence: 12 givenname: Jerome I surname: Rotter fullname: Rotter, Jerome I organization: The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA – sequence: 13 givenname: Ani surname: Manichaikul fullname: Manichaikul, Ani organization: Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA 22908, USA – sequence: 14 givenname: Ruth J F surname: Loos fullname: Loos, Ruth J F organization: The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark – sequence: 15 givenname: Eimear E surname: Kenny fullname: Kenny, Eimear E organization: The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA – sequence: 16 givenname: Thomas W surname: Blackwell fullname: Blackwell, Thomas W organization: TOPMed Informatics Research Center, University of Michigan, Department of Biostatistics, Ann Arbor, MI 48109, USA – sequence: 17 givenname: Albert V surname: Smith fullname: Smith, Albert V organization: TOPMed Informatics Research Center, University of Michigan, Department of Biostatistics, Ann Arbor, MI 48109, USA – sequence: 18 givenname: Goo surname: Jun fullname: Jun, Goo organization: Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA – sequence: 19 givenname: Fritz J surname: Sedlazeck fullname: Sedlazeck, Fritz J organization: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA – sequence: 20 givenname: Ginger surname: Metcalf fullname: Metcalf, Ginger organization: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA – sequence: 21 givenname: Eric surname: Boerwinkle fullname: Boerwinkle, Eric organization: Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA – sequence: 22 givenname: Laura M surname: Raffield fullname: Raffield, Laura M organization: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA – sequence: 23 givenname: Alex P surname: Reiner fullname: Reiner, Alex P organization: Department of Epidemiology, University of Washington, Seattle, WA 98195, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA – sequence: 24 givenname: Paul L surname: Auer fullname: Auer, Paul L email: pauer@mcw.edu organization: Division of Biostatistics, Institute for Health and Equity, and Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: pauer@mcw.edu – sequence: 25 givenname: Yun surname: Li fullname: Li, Yun email: yunli@med.unc.edu organization: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: yunli@med.unc.edu |
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| Title | TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data |
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