Common Genetic Variants Associate with Serum Phosphorus Concentration
Year: 2010
Type: article
Study design: Observational Study
Abstract: Phosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations, genetic variation may determine interindividual variation in phosphorus metabolism. Here, we report a comprehensive genome-wide association study of serum phosphorus concentration. We evaluated 16,264 participants of European ancestry from the Cardiovascular Heath Study, Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and the Rotterdam Study. We excluded participants with an estimated GFR <45 ml/min per 1.73 m(2) to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the HapMap and combined study-specific findings using meta-analysis. We tested top polymorphisms from discovery cohorts in a 5444-person replication sample. Polymorphisms in seven loci with minor allele frequencies 0.08 to 0.49 associate with serum phosphorus concentration (P = 3.5 x 10(-16) to 3.6 x 10(-7)). Three loci were near genes encoding the kidney-specific type IIa sodium phosphate co-transporter (SLC34A1), the calcium-sensing receptor (CASR), and fibroblast growth factor 23 (FGF23), proteins that contribute to phosphorus metabolism. We also identified genes encoding phosphatases, kinases, and phosphodiesterases that have yet-undetermined roles in phosphorus homeostasis. In the replication sample, five of seven top polymorphisms associate with serum phosphorous concentrations (P < 0.05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation.
Authors: Bryan Kestenbaum, Nicole L. Glazer, Anna Köttgen, Janine F. Felix, Shih-Jen Hwang, Yongmei Liu, Kurt Lohman, Stephen B. Kritchevsky, Dorothy B. Hausman, Ann-Kristin Petersen, Christian Gieger, Janina S. Ried, Thomas Meitinger, Tim M. Strom, H. Erich Wichmann, Harry Campbell, Caroline Hayward, Igor Rudan, Ian H. de Boer, Bruce M. Psaty, Kenneth M. Rice, Yii-Der Ida Chen, Man Li, Dan E. Arking, Eric Boerwinkle, Josef Coresh, Qiong Yang, Daniel Levy, Frank J.A. van Rooij, Abbas Dehghan, Fernando Rivadeneira, André G. Uitterlinden, Albert Hofman, Cornelia M. van Duijn, Michael G. Shlipak, W.H. Linda Kao, Jacqueline C.M. Witteman, David S. Siscovick, Caroline S. Fox
Institution: University of Washington
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: School of Medicine, Boston University, Wellcome Trust, Cedars-Sinai Medical Center, European Commission, ZonMw, Erasmus Universiteit Rotterdam, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, National Institutes of Health, U.S. Public Health Service, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G1153142239, G118440752, G1220223050, G1325221871, G1332411685, G136105103, G1462415530, G2070131968, G2078309758, G215333750, G2194386449, G250621538, G25881238, G277826483, G278975345, G2800149121, G2818913090, G297113894, G3042145041, G3236609591, G328935669, G36937976, G3839646794, G390162502, G395403786, G4048755144, G423252844, G4705346009, G494123624, G5164707915, G5274979365, G528395701, G536099884, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, G5451084504, Epidemiology of Venous Thrombosis and Pulmonary Embolism, CHS Events Follow-up Study, G6203107232, G6226795708, G783845518, G786153652, G793702358, G7999488110, G80149192, G812579647, G8486527673, G8593276544, G9000124674, From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G905887895, G931818222
OpenAlex ID: W2133852929