Genome-Wide Meta-Analysis for Serum Calcium Identifies Significantly Associated SNPs near the Calcium-Sensing Receptor (CASR) Gene
Author(s)
Type
Journal Article
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 6.3610-37 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 = 1.1610-21), 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 = 1.02610-4). 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.
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 6.3610-37 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 = 1.1610-21), 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 = 1.02610-4). 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.
Date Issued
2010-07-01
Date Acceptance
2010-06-17
Citation
PLOS Genetics, 2010, 6 (7)
ISSN
1553-7390
Publisher
Public Library of Science
Journal / Book Title
PLOS Genetics
Volume
6
Issue
7
Copyright Statement
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public
domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
License URL
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Grant Number
G0801056B
G0801056/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENETICS & HEREDITY
BONE-MINERAL DENSITY
CORONARY-HEART-DISEASE
PRIMARY HYPERPARATHYROIDISM
HYPOCALCIURIC HYPERCALCEMIA
CARDIOVASCULAR MORTALITY
MYOCARDIAL-INFARCTION
A986S POLYMORPHISM
COMMON VARIANT
ADULT
LOCI
Publication Status
Published
Article Number
e1001035