학술논문
Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene.
Document Type
article
Author
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 Desilva; Paul 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
Source
PLoS Genetics, Vol 6, Iss 7, p e1001035 (2010)
Subject
Language
English
ISSN
1553-7390
1553-7404
1553-7404
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 x 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 x 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 x 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.