Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.

TitleMeta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.
Publication TypeJournal Article
Year of Publication2013
AuthorsO'Seaghdha CM, Wu H, Yang Q, Kapur K, Guessous I, Zuber AMercier, Köttgen A, Stoudmann C, Teumer A, Kutalik Z et al.
Corporate AuthorsSUNLIGHT Consortium, GEFOS Consortium
JournalPLoS Genet
Volume9
Issue9
Paginatione1003796
Date Published2013
ISSN1553-7404
Abstract

Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤ 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

DOI10.1371/journal.pgen.1003796
Alternate JournalPLoS Genet.
PubMed ID24068962
PubMed Central IDPMC3778004
Grant List064890 / / Wellcome Trust / United Kingdom
081682 / / Wellcome Trust / United Kingdom
1R01AG032098-01A1 / AG / NIA NIH HHS / United States
263 MD 821336 / MD / NIMHD NIH HHS / United States
263 MD 9164 / MD / NIMHD NIH HHS / United States
AG-023629 / AG / NIA NIH HHS / United States
AG-027058 / AG / NIA NIH HHS / United States
AG-15928 / AG / NIA NIH HHS / United States
AG-20098 / AG / NIA NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
HHSN268200782096C / / PHS HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100006C / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201200036C / / PHS HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
HSN268201100012C / / PHS HHS / United States
KO3598/2-1 / / PHS HHS / United States
N01 HC-15103 / HC / NHLBI NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
N01- HC-75150 / HC / NHLBI NIH HHS / United States
N01-AG-1-2100 / AG / NIA NIH HHS / United States
N01-HC- 85239 / HC / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
N01-HC-35129 / HC / NHLBI NIH HHS / United States
N01-HC-45133 / HC / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01AG62101 / AG / NIA NIH HHS / United States
N01AG62103 / AG / NIA NIH HHS / United States
N01AG62106 / AG / NIA NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
UL1RR033176 / RR / NCRR NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States

Previous Publications