Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene.
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.
Kapur
Karen
K
Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
Johnson
Toby
T
Beckmann
Noam D
ND
Sehmi
Joban
J
Tanaka
Toshiko
T
Kutalik
Zoltán
Z
Styrkarsdottir
Unnur
U
Zhang
Weihua
W
Marek
Diana
D
Gudbjartsson
Daniel F
DF
Milaneschi
Yuri
Y
Holm
Hilma
H
Diiorio
Angelo
A
Waterworth
Dawn
D
Li
Yun
Y
Singleton
Andrew B
AB
Bjornsdottir
Unnur S
US
Sigurdsson
Gunnar
G
Hernandez
Dena G
DG
Desilva
Ranil
R
Elliott
Paul
P
Eyjolfsson
Gudmundur I
GI
Guralnik
Jack M
JM
Scott
James
J
Thorsteinsdottir
Unnur
U
Bandinelli
Stefania
S
Chambers
John
J
Stefansson
Kari
K
Waeber
Gérard
G
Ferrucci
Luigi
L
Kooner
Jaspal S
JS
Mooser
Vincent
V
Vollenweider
Peter
P
Beckmann
Jacques S
JS
Bochud
Murielle
M
Bergmann
Sven
S
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
D044169:Receptors, Calcium-Sensing; D002118:Calcium