TY - JOUR
T1 - Common genetic variants associate with serum phosphorus concentration
AU - Kestenbaum, Bryan
AU - Glazer, Nicole L.
AU - Köttgen, Anna
AU - Felix, Janine F.
AU - Hwang, Shih Jen
AU - Liu, Yongmei
AU - Lohman, Kurt
AU - Kritchevsky, Stephen B.
AU - Hausman, Dorothy B.
AU - Petersen, Ann Kristin
AU - Gieger, Christian
AU - Ried, Janina S.
AU - Meitinger, Thomas
AU - Strom, Tim M.
AU - Erich Wichmann, H.
AU - Campbell, Harry
AU - Hayward, Caroline
AU - Rudan, Igor
AU - De Boer, Ian H.
AU - Psaty, Bruce M.
AU - Rice, Kenneth M.
AU - Chen, Yii Der Ida
AU - Li, Man
AU - Arking, Dan E.
AU - Boerwinkle, Eric
AU - Coresh, Josef
AU - Yang, Qiong
AU - Levy, Daniel
AU - Van Rooij, Frank J.A.
AU - Dehghan, Abbas
AU - Rivadeneira, Fernando
AU - Uitterlinden, AndréG
AU - Hofman, Albert
AU - Van Duijn, Cornelia M.
AU - Shlipak, Michael G.
AU - Linda Kao, W. H.
AU - Witteman, Jacqueline C.M.
AU - Siscovick, David S.
AU - Fox, Caroline S.
PY - 2010/7
Y1 - 2010/7
N2 - 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 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 × 10-16 to 3.6 × 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.
AB - 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 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 × 10-16 to 3.6 × 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.
UR - http://www.scopus.com/inward/record.url?scp=77954575665&partnerID=8YFLogxK
U2 - 10.1681/ASN.2009111104
DO - 10.1681/ASN.2009111104
M3 - Article
C2 - 20558539
AN - SCOPUS:77954575665
SN - 1046-6673
VL - 21
SP - 1223
EP - 1232
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 7
ER -