Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene

Karen Kapur, Toby Johnson, Noam D. Beckmann, Joban Sehmi, Toshiko Tanaka, Zoltán Kutalik, Unnur Styrkarsdottir, Weihua Zhang, Diana Marek, Daniel F. Gudbjartsson, Yuri Milaneschi, Hilma Holm, Angelo DiIorio, Dawn Waterworth, Yun Li, Andrew B. Singleton, Unnur S. Bjornsdottir, Gunnar Sigurdsson, Dena G. Hernandez, Ranil de SilvaPaul Elliott, Gudmundur I. Eyjolfsson, Jack M. Guralnik, James Scott, Unnur Thorsteinsdottir, Stefania Bandinelli, John Chambers, Kari Stefansson, Gérard Waeber, Luigi Ferrucci, Jaspal S. Kooner, Vincent Mooser, Peter Vollenweider, Jacques S. Beckmann, Murielle Bochud, Sven Bergmann

Research output: Contribution to journalArticle

Abstract

Calcium has a pivotal role in biological functions, and serum calcium levels have been associated with numerous disorders of bone and mineral metabolism, as well as with cardiovascular mortality. Here we report results from a genome-wide association study of serum calcium, integrating data from four independent cohorts including a total of 12,865 individuals of European and Indian Asian descent. Our meta-analysis shows that serum calcium is associated with SNPs in or near the calcium-sensing receptor (CASR) gene on 3q13. The top hit with a p-value of 6.3×10-37 is rs1801725, a missense variant, explaining 1.26% of the variance in serum calcium. This SNP had the strongest association in individuals of European descent, while for individuals of Indian Asian descent the top hit was rs17251221 (p = 1.1×10-21), a SNP in strong linkage disequilibrium with rs1801725. The strongest locus in CASR was shown to replicate in an independent Icelandic cohort of 4,126 individuals (p = 1.02×10-4). This genome-wide meta-analysis shows that common CASR variants modulate serum calcium levels in the adult general population, which confirms previous results in some candidate gene studies of the CASR locus. This study highlights the key role of CASR in calcium regulation.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalPLoS Genetics
Volume6
Issue number7
DOIs
StatePublished - Jul 2010
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

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    Kapur, K., Johnson, T., Beckmann, N. D., Sehmi, J., Tanaka, T., Kutalik, Z., Styrkarsdottir, U., Zhang, W., Marek, D., Gudbjartsson, D. F., Milaneschi, Y., Holm, H., DiIorio, A., Waterworth, D., Li, Y., Singleton, A. B., Bjornsdottir, U. S., Sigurdsson, G., Hernandez, D. G., ... Bergmann, S. (2010). Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene. PLoS Genetics, 6(7), 1-12. https://doi.org/10.1371/journal.pgen.1001035