TY - JOUR
T1 - Genome-wide meta-analysis for serum calcium identifies significantly associated SNPs near the calcium-sensing receptor (CASR) gene
AU - Kapur, Karen
AU - Johnson, Toby
AU - Beckmann, Noam D.
AU - Sehmi, Joban
AU - Tanaka, Toshiko
AU - Kutalik, Zoltán
AU - Styrkarsdottir, Unnur
AU - Zhang, Weihua
AU - Marek, Diana
AU - Gudbjartsson, Daniel F.
AU - Milaneschi, Yuri
AU - Holm, Hilma
AU - DiIorio, Angelo
AU - Waterworth, Dawn
AU - Li, Yun
AU - Singleton, Andrew B.
AU - Bjornsdottir, Unnur S.
AU - Sigurdsson, Gunnar
AU - Hernandez, Dena G.
AU - de Silva, Ranil
AU - Elliott, Paul
AU - Eyjolfsson, Gudmundur I.
AU - Guralnik, Jack M.
AU - Scott, James
AU - Thorsteinsdottir, Unnur
AU - Bandinelli, Stefania
AU - Chambers, John
AU - Stefansson, Kari
AU - Waeber, Gérard
AU - Ferrucci, Luigi
AU - Kooner, Jaspal S.
AU - Mooser, Vincent
AU - Vollenweider, Peter
AU - Beckmann, Jacques S.
AU - Bochud, Murielle
AU - Bergmann, Sven
N1 - Funding Information:
Vincent Mooser and Dawn Waterworth are full-time employees of GlaxoSmithKline, a pharmaceutical company. Peter Vollenweider and Gerard Waeber received financial support from GlaxoSmithKline to build the CoLaus study. Daniel F Gudbjarsson, Unnur Styrkarsdottir, Hilma Holm, Unnur Thorsteinsdottir and Kari Stefansson are employees of deCODE genetics, a biotechnology company.
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77957376468&partnerID=8YFLogxK
U2 - 10.1371/journal.pgen.1001035
DO - 10.1371/journal.pgen.1001035
M3 - Article
C2 - 20661308
AN - SCOPUS:77957376468
SN - 1553-7390
VL - 6
SP - 1
EP - 12
JO - PLoS Genetics
JF - PLoS Genetics
IS - 7
ER -