Common Genetic Variants Associate with Serum Phosphorus Concentration

Bryan Kestenbaum, Nicole L. Glazer, Anna Koettgen, 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. PsatyKenneth 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, Andre 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

Research output: Contribution to journalArticlepeer-review


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 m2 to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the Hap Map and combined study-specific findings using meta-analysis. We tested top polynnorphisms 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-v). Three loci were near genes encoding the kidney-specific type Ila 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 yetundetermined 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.

Original languageEnglish
Pages (from-to)1223-1232
Number of pages10
JournalJournal of the American Society of Nephrology
Issue number7
Publication statusPublished - Jul 2010


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