Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals
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Holzinger, Emily R, et al. Discovery and Replication of Snp-snp Interactions for Quantitative Lipid Traits In Over 60,000 Individuals. BioMed Central, 2017. https://doi.org/10.17615/dfgf-ck41APA
Holzinger, E., Verma, S., Moore, C., Hall, M., De, R., Gilbert Diamond, D., Lanktree, M., Pankratz, N., Amuzu, A., Burt, A., Dale, C., Dudek, S., Furlong, C., Gaunt, T., Kim, D., Riess, H., Sivapalaratnam, S., Tragante, V., Van Iperen, E., Brautbar, A., Carrell, D., Crosslin, D., Jarvik, G., Kuivaniemi, H., Kullo, I., Larson, E., Rasmussen Torvik, L., Tromp, G., Baumert, J., Cruickshanks, K., Farrall, M., Hingorani, A., Hovingh, G., Kleber, M., Klein, B., Klein, R., Koenig, W., Lange, L., Mӓrz, W., North, K., Onland Moret, N., Reiner, A., Talmud, P., Van Der Schouw, Y., Wilson, J., Kivimaki, M., Kumari, M., Moore, J., Drenos, F., Asselbergs, F., Keating, B., & Ritchie, M. (2017). Discovery and replication of SNP-SNP interactions for quantitative lipid traits in over 60,000 individuals. BioMed Central. https://doi.org/10.17615/dfgf-ck41Chicago
Holzinger, Emily R, Shefali S Verma, Carrie B Moore, Molly Hall, Rishika De, Diane Gilbert Diamond, Matthew B Lanktree et al. 2017. Discovery and Replication of Snp-Snp Interactions for Quantitative Lipid Traits In Over 60,000 Individuals. BioMed Central. https://doi.org/10.17615/dfgf-ck41- Creator
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Holzinger, Emily R
- Other Affiliation: Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institute for General Medical Sciences, National Institutes of Health, Baltimore, USA
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Verma, Shefali S
- Other Affiliation: The Center for Systems Genomics, The Pennsylvania State University, University Park, State College, USA
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Moore, Carrie B
- Other Affiliation: Department of Surgery, Duke University, Durham, USA
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Hall, Molly
- Other Affiliation: The Center for Systems Genomics, The Pennsylvania State University, University Park, State College, USA
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De, Rishika
- Other Affiliation: Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, USA
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Gilbert-Diamond, Diane
- Other Affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, USA
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Lanktree, Matthew B
- Other Affiliation: Department of Medicine, McMaster University, Hamilton, Canada
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Pankratz, Nathan
- Other Affiliation: Department of Lab Medicine and Pathology, University of Minnesota, Minneapolis, USA
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Amuzu, Antoinette
- Other Affiliation: London School of Hygiene and Tropical Medicine, London, UK
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Burt, Amber
- Other Affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, USA
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Dale, Caroline
- Other Affiliation: London School of Hygiene and Tropical Medicine, London, UK
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Dudek, Scott
- Other Affiliation: The Center for Systems Genomics, The Pennsylvania State University, University Park, State College, USA
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Furlong, Clement E
- Other Affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, USA
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Gaunt, Tom R
- Other Affiliation: MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
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Kim, Daniel S
- Other Affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, USA
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Riess, Helene
- Other Affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
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Sivapalaratnam, Suthesh
- Other Affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
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Tragante, Vinicius
- Other Affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Medical Genetics, Biomedical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
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van Iperen, Erik P
- Other Affiliation: Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands
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Brautbar, Ariel
- Other Affiliation: Department of Medical Genetics, Marshfield Clinic, Marshfield, USA
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Carrell, David S
- Other Affiliation: Group Health Research Institute, Group Health Cooperative, Seattle, USA
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Crosslin, David R
- Other Affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, USA
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Jarvik, Gail P
- Other Affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, USA
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Kuivaniemi, Helena
- Other Affiliation: Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Tygerberg, South Africa
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Kullo, Iftikhar J
- Other Affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, USA
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Larson, Eric B
- Other Affiliation: Group Health Research Institute, Group Health Cooperative, Seattle, USA
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Rasmussen-Torvik, Laura J
- Other Affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, USA
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Tromp, Gerard
- Other Affiliation: Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Tygerberg, South Africa
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Baumert, Jens
- Other Affiliation: Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
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Cruickshanks, Karen J
- Other Affiliation: Department of Population Health Sciences, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, USA
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Farrall, Martin
- Other Affiliation: Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
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Hingorani, Aroon D
- Other Affiliation: Department of Epidemiology and Public Health, UCL Institute of Epidemiology & Health Care, University College London, London, UK
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Hovingh, G. K
- Other Affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
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Kleber, Marcus E
- Other Affiliation: Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
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Klein, Barbara E
- Other Affiliation: Department of Population Health Sciences, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, USA
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Klein, Ronald
- Other Affiliation: Department of Population Health Sciences, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, USA
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Koenig, Wolfgang
- Other Affiliation: Department of Internal Medicine II – Cardiology, University of Ulm Medical Centre, Ulm, Germany
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Lange, Leslie
- Affiliation: School of Medicine, Department of Genetics
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Mӓrz, Winfried
- Other Affiliation: Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; Synlab Academy, Synlab Services GmbH, Mannheim, Germany
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North, Kari
- Affiliation: Gillings School of Global Public Health, Department of Epidemiology
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Onland-Moret, N. Charlotte
- Other Affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
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Reiner, Alex P
- Other Affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA
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Talmud, Philippa J
- Other Affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK
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van der Schouw, Yvonne T
- Other Affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
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Wilson, James G
- Other Affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, USA
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Kivimaki, Mika
- Other Affiliation: Department of Epidemiology and Public Health, UCL Institute of Epidemiology & Health Care, University College London, London, UK
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Kumari, Meena
- Other Affiliation: Department of Epidemiology and Public Health, UCL Institute of Epidemiology & Health Care, University College London, London, UK; ISER, University of Essex, Essex, UK
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Moore, Jason H
- Other Affiliation: Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
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Drenos, Fotios
- Other Affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK; Centre of Cardiovascular Genetics, Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK
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Asselbergs, Folkert W
- Other Affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands; Centre of Cardiovascular Genetics, Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK
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Keating, Brendan J
- Other Affiliation: Division of Genetics, The Children’s Hospital of Philadelphia, Philadelphia, USA; Division of Transplantation, Department of Surgery, University of Pennsylvania, Philadelphia, USA
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Ritchie, Marylyn D
- Other Affiliation: Biomedical and Translational Informatics, Geisinger Clinic, Danville, USA
- Abstract
- Abstract Background The genetic etiology of human lipid quantitative traits is not fully elucidated, and interactions between variants may play a role. We performed a gene-centric interaction study for four different lipid traits: low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). Results Our analysis consisted of a discovery phase using a merged dataset of five different cohorts (n = 12,853 to n = 16,849 depending on lipid phenotype) and a replication phase with ten independent cohorts totaling up to 36,938 additional samples. Filters are often applied before interaction testing to correct for the burden of testing all pairwise interactions. We used two different filters: 1. A filter that tested only single nucleotide polymorphisms (SNPs) with a main effect of p < 0.001 in a previous association study. 2. A filter that only tested interactions identified by Biofilter 2.0. Pairwise models that reached an interaction significance level of p < 0.001 in the discovery dataset were tested for replication. We identified thirteen SNP-SNP models that were significant in more than one replication cohort after accounting for multiple testing. Conclusions These results may reveal novel insights into the genetic etiology of lipid levels. Furthermore, we developed a pipeline to perform a computationally efficient interaction analysis with multi-cohort replication.
- Date of publication
- July 24, 2017
- DOI
- Identifier
- Resource type
- Article
- Rights statement
- In Copyright
- Rights holder
- The Author(s).
- Language
- English
- Bibliographic citation
- BioData Mining. 2017 Jul 24;10(1):25
- Publisher
- BioMed Central
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