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Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels.
Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
| Title | Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | O'Seaghdha, CM, Yang, Q, Glazer, NL, Leak, TS, Dehghan, A, Smith, AV, Kao, LWH, Lohman, K, Hwang, S-J, Johnson, AD, Hofman, A, Uitterlinden, AG, Chen, Y-DI, Brown, EM, Siscovick, DS, Harris, TB, Psaty, BM, Coresh, J, Gudnason, V, Witteman, JC, Liu, YMei, Kestenbaum, BR, Fox, CS, Köttgen, A |
| Corporate/Institutional Authors | GEFOS Consortium, |
| Journal | Hum Mol Genet |
| Volume | 19 |
| Issue | 21 |
| Pagination | 4296-303 |
| Date Published | 2010 Nov 01 |
| ISSN | 1460-2083 |
| Keywords | Adult, Calcium, Female, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Calcium-Sensing |
| Abstract | <p>Serum calcium levels are tightly regulated. We performed genome-wide association studies (GWAS) in population-based studies participating in the CHARGE Consortium to uncover common genetic variations associated with total serum calcium levels. GWAS of serum calcium concentrations was performed in 20 611 individuals of European ancestry for ∼2.5 million genotyped and imputed single-nucleotide polymorphisms (SNPs). The SNP with the lowest P-value was rs17251221 (P = 2.4 * 10(-22), minor allele frequency 14%) in the calcium-sensing receptor gene (CASR). This lead SNP was associated with higher serum calcium levels [0.06 mg/dl (0.015 mmol/l) per copy of the minor G allele] and accounted for 0.54% of the variance in serum calcium concentrations. The identification of variation in CASR that influences serum calcium concentration confirms the results of earlier candidate gene studies. The G allele of rs17251221 was also associated with higher serum magnesium levels (P = 1.2 * 10(-3)), lower serum phosphate levels (P = 2.8 * 10(-7)) and lower bone mineral density at the lumbar spine (P = 0.038), but not the femoral neck. No additional genomic loci contained SNPs associated at genome-wide significance (P < 5 * 10(-8)). These associations resemble clinical characteristics of patients with familial hypocalciuric hypercalcemia, an autosomal-dominant disease arising from rare inactivating mutations in the CASR gene. We conclude that common genetic variation in the CASR gene is associated with similar but milder features in the general population.</p> |
| DOI | 10.1093/hmg/ddq342 |
| Alternate Journal | Hum. Mol. Genet. |
| PubMed ID | 20705733 |
| PubMed Central ID | PMC2951868 |
| Grant List | UL1RR025005 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States R01 AG027002 / AG / NIA NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01AG62101 / AG / NIA NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States 1R01AG032098-01A1 / AG / NIA NIH HHS / United States HHSN268200625226C / / PHS HHS / United States N01-HC-85079-86 / HC / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-15103 / HC / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States R01 AG032098 / AG / NIA NIH HHS / United States / / Intramural NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States M01RR00425 / RR / NCRR NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States K23 DK63274-01 / DK / NIDDK NIH HHS / United States N01-AG-12100 / AG / NIA NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01AG62103 / AG / NIA NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States HHSN268200782096C / / PHS HHS / United States N01AG62106 / AG / NIA NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States |