title: Association of common variants in the calcium-sensing receptor gene with serum calcium levels in East Asians.
abstract: Calcium is a universal intracellular messenger that has an important role in controlling various cellular processes. In this study, we explored genetic polymorphisms to identify novel loci influencing serum calcium levels in East Asians through a two-stage genome-wide association study with the sample of 8642 unrelated Koreans (4558 for discovery and 4093 for replication). Using single-nucleotide polymorphism (SNP) arrays, we discovered 963 associated SNPs in stage 1, and replicated 105 SNPs among them in stage 2. We examined them in a combined set of stage 1 and 2 samples and observed that 65 SNPs were significantly associated with serum calcium levels. Among them, rs13068893 in the CASR gene showed the strongest significance (P=3.85 × 10(-8)). Considering the high allele frequency and significance level of the rs13068893C>G in the CASR gene, this SNP may have a key role in regulating the serum calcium level. We also successfully replicated the four loci (CASR, CSTA, DGKD and GCKR) using our data set that have been previously reported to be significantly associated with calcium levels in Europeans and Indians. Further studies with more East Asian subjects or meta-analyses on them may enable validation of our results and identification of novel genetic loci associated with serum calcium levels.
authors.affiliation: Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Nadimuthu
authors.initials: N
authors.lastname: Vinayagamoorthy
authors.affiliation: Department of Medical Education, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Yim
authors.affiliation: Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Park
authors.affiliation: Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea.
authors.forename: Bong-Jo
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yeun-Jun
authors.initials: YJ
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D002118:Calcium / Q000097:blood*; D005202:Asia, Eastern / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044169:Receptors, Calcium-Sensing / Q000235:genetics*
chemical_list: C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing; D002118:Calcium