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Common genetic variants associate with serum phosphorus concentration.
Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
| Title | Common genetic variants associate with serum phosphorus concentration. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | Kestenbaum, B, Glazer, NL, Köttgen, A, Felix, JF, Hwang, S-J, Liu, Y, Lohman, K, Kritchevsky, SB, Hausman, DB, Petersen, A-K, Gieger, C, Ried, JS, Meitinger, T, Strom, TM, Wichmann, EH, Campbell, H, Hayward, C, Rudan, I, de Boer, IH, Psaty, BM, Rice, KM, Chen, Y-DI, Li, M, Arking, DE, Boerwinkle, E, Coresh, J, Yang, Q, Levy, D, van Rooij, FJA, Dehghan, A, Rivadeneira, F, Uitterlinden, AG, Hofman, A, van Duijn, CM, Shlipak, MG, Kao, LWH, Witteman, JCM, Siscovick, DS, Fox, CS |
| Journal | J Am Soc Nephrol |
| Volume | 21 |
| Issue | 7 |
| Pagination | 1223-32 |
| Date Published | 2010 Jul |
| ISSN | 1533-3450 |
| Keywords | Adult, Aged, European Continental Ancestry Group, Female, Fibroblast Growth Factors, Gene Frequency, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Kidney, Male, Middle Aged, Phosphorus, Polymorphism, Single Nucleotide, Receptors, Calcium-Sensing, Sex Factors, Sodium-Phosphate Cotransporter Proteins, Type IIa |
| Abstract | <p>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.</p> |
| DOI | 10.1681/ASN.2009111104 |
| Alternate Journal | J. Am. Soc. Nephrol. |
| PubMed ID | 20558539 |
| PubMed Central ID | PMC3152230 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States U01-HL080295 / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States MC_U127561128 / / Medical Research Council / United Kingdom N01 HC015103 / HC / NHLBI NIH HHS / United States M01 RR000069 / RR / NCRR NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States HHSN268200625226C / / PHS HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States M01RR00069 / RR / NCRR NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States R01 HL084443 / HL / NHLBI NIH HHS / United States R01 AG027002 / AG / NIA NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States Z99 HL999999 / / Intramural NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States P30 AG021332 / AG / NIA NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States |