title: Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene.
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.
authors.affiliation: Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Karen
authors.initials: K
authors.lastname: Kapur
authors.forename: Toby
authors.initials: T
authors.lastname: Johnson
authors.forename: Noam D
authors.initials: ND
authors.lastname: Beckmann
authors.forename: Joban
authors.initials: J
authors.lastname: Sehmi
authors.forename: Toshiko
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authors.lastname: Tanaka
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kutalik
authors.forename: Unnur
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authors.lastname: Styrkarsdottir
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhang
authors.forename: Diana
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authors.lastname: Marek
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: Yuri
authors.initials: Y
authors.lastname: Milaneschi
authors.forename: Hilma
authors.initials: H
authors.lastname: Holm
authors.forename: Angelo
authors.initials: A
authors.lastname: Diiorio
authors.forename: Dawn
authors.initials: D
authors.lastname: Waterworth
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Unnur S
authors.initials: US
authors.lastname: Bjornsdottir
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sigurdsson
authors.forename: Dena G
authors.initials: DG
authors.lastname: Hernandez
authors.forename: Ranil
authors.initials: R
authors.lastname: Desilva
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
authors.forename: Gudmundur I
authors.initials: GI
authors.lastname: Eyjolfsson
authors.forename: Jack M
authors.initials: JM
authors.lastname: Guralnik
authors.forename: James
authors.initials: J
authors.lastname: Scott
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: John
authors.initials: J
authors.lastname: Chambers
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Jaspal S
authors.initials: JS
authors.lastname: Kooner
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Murielle
authors.initials: M
authors.lastname: Bochud
authors.forename: Sven
authors.initials: S
authors.lastname: Bergmann
mesh_terms: D002118:Calcium / Q000097:blood*; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D044169:Receptors, Calcium-Sensing / Q000235:genetics*; D044465:White People / Q000706:statistics & numerical data
chemical_list: D044169:Receptors, Calcium-Sensing; D002118:Calcium