Common variants associated with plasma triglycerides and risk for coronary artery disease · SciRah

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Common variants associated with plasma triglycerides and risk for coronary artery disease

Ron Do^{a b c d e}, Cristen J. Willer^{f g h i}, Ellen M. Schmidt^g, Sebanti Sengupta^f, Chi Gao^{b c e}, Gina Marie Peloso^{c e j}, Stefan Gustafsson^{k l}, Stavroula Kanoni^m, Andrea Ganna^{k l n}, Jin Chen^f, Martin L. Buchkovich^o, Samia Mora

Nature Genetics Nature Portfolio2013-10-06 864 citations36 references

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Abstract

Sekar Kathiresan and colleagues examine 185 common variants using a modified mendelian randomization approach and provide evidence supporting a causal role of triglyceride-rich lipoproteins in the development of coronary artery disease. Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10−8 for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

TL;DRThe use of 185 common variants recently mapped for plasma lipids to examine the role of triglycerides in risk for CAD suggests that triglyceride-rich lipoproteins causally influence risk for CAD. (Semantic Scholar)

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Discussion

^a1] Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. [4] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
^bCardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
^cCenter for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
^dDepartment of Medicine, Harvard Medical School, Boston, Massachusetts, USA
^eProgram in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
^fDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA
^gDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA
^hDepartment of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA
ⁱDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA
^jDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
^kDepartment of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden
^lScience for Life Laboratory, Uppsala University, Uppsala, Sweden
^mWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
ⁿDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
^oDepartment of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA
^pDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
^qDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
^rDepartment of Medical Genetics, University of Lausanne, Lausanne, Switzerland
^sService of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland
^tDivision of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
^uDepartment of Epidemiology, Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam, The Netherlands
^vDepartment of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
^wMedical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
^xCenter for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
^yDepartment of Specialities of Medicine, Cardiology, Geneva University Hospital, Geneva, Switzerland
^zEstonian Genome Center of the University of Tartu, Tartu, Estonia
^aaInstitute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
^abDepartment of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA
^acWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
^adCentre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
^aeDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK
^afDepartment of Public Health, Hjelt Institute, University of Helsinki, Helsinki, Finland
^agCentre For Paediatric Epidemiology and Biostatistics/Medical Research Council (MRC) Centre of Epidemiology for Child Health, University College London Institute of Child Health, London, UK
^ahCentre for Medical Systems Biology, Leiden, The Netherlands