1. Identifying common genetic variants in blood pressure due to polygenic pleiotropy with associated phenotypes.
- Author
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Andreassen, Ole A, McEvoy, Linda K, Thompson, Wesley K, Wang, Yunpeng, Reppe, Sjur, Schork, Andrew J, Zuber, Verena, Barrett-Connor, Elizabeth, Gautvik, Kaare, Aukrust, Pål, Karlsen, Tom H, Djurovic, Srdjan, Desikan, Rahul S, Dale, Anders M, and International Consortium for Blood Pressure Genome-Wide Association Studies, Genetic Factors for Osteoporosis Consortium
- Subjects
International Consortium for Blood Pressure Genome-Wide Association Studies ,Genetic Factors for Osteoporosis Consortium ,Humans ,Arthritis ,Rheumatoid ,Celiac Disease ,Hypertension ,Diabetes Mellitus ,Obesity ,Schizophrenia ,Blood Pressure ,Bone Density ,Multifactorial Inheritance ,Phenotype ,Polymorphism ,Single Nucleotide ,Hyperlipidemias ,Genetic Variation ,Genome-Wide Association Study ,Genetic Pleiotropy ,arterial pressure ,comorbidity ,genetic pleiotropy ,genome-wide association study ,International Consortium for Blood Pressure Genome-Wide Association Studies ,Genetic Factors for Osteoporosis Consortium ,Arthritis ,Rheumatoid ,Polymorphism ,Single Nucleotide ,Genetics ,Cardiovascular ,Diabetes ,Prevention ,Nutrition ,Biotechnology ,Human Genome ,2.1 Biological and endogenous factors ,Metabolic and Endocrine ,Cardiovascular System & Hematology ,Clinical Sciences ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services - Abstract
Blood pressure is a critical determinant of cardiovascular morbidity and mortality. It is affected by environmental factors, but has a strong heritable component. Despite recent large genome-wide association studies, few genetic risk factors for blood pressure have been identified. Epidemiological studies suggest associations between blood pressure and several diseases and traits, which may partly arise from a shared genetic basis (genetic pleiotropy). Using genome-wide association studies summary statistics and a genetic pleiotropy-informed conditional false discovery rate method, we systematically investigated genetic overlap between systolic blood pressure (SBP) and 12 comorbid traits and diseases. We found significant enrichment of single nucleotide polymorphisms associated with SBP as a function of their association with body mass index, low-density lipoprotein, waist/hip ratio, schizophrenia, bone mineral density, type 1 diabetes mellitus, and celiac disease. In contrast, the magnitude of enrichment due to shared polygenic effects was smaller with the other phenotypes (triglycerides, high-density lipoproteins, type 2 diabetes mellitus, rheumatoid arthritis, and height). Applying the conditional false discovery rate method to the enriched phenotypes, we identified 62 loci associated with SBP (false discovery rate
- Published
- 2014