serval:BIB_2AD446B425B4
Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.
10.1371/journal.pgen.1003796
000325076600054
24068962
O'Seaghdha
C.M.
author
Wu
H.
author
Yang
Q.
author
Kapur
K.
author
Guessous
I.
author
Zuber
A.M.
author
Köttgen
A.
author
Stoudmann
C.
author
Teumer
A.
author
Kutalik
Z.
author
Mangino
M.
author
Dehghan
A.
author
Zhang
W.
author
Eiriksdottir
G.
author
Li
G.
author
Tanaka
T.
author
Portas
L.
author
Lopez
L.M.
author
Hayward
C.
author
Lohman
K.
author
Matsuda
K.
author
Padmanabhan
S.
author
Firsov
D.
author
Sorice
R.
author
Ulivi
S.
author
Brockhaus
A.C.
author
Kleber
M.E.
author
Mahajan
A.
author
Ernst
F.D.
author
Gudnason
V.
author
Launer
L.J.
author
Mace
A.
author
Boerwinckle
E.
author
Arking
D.E.
author
Tanikawa
C.
author
Nakamura
Y.
author
Brown
M.J.
author
Gaspoz
J.M.
author
Theler
J.M.
author
Siscovick
D.S.
author
Psaty
B.M.
author
Bergmann
S.
author
Vollenweider
P.
author
Vitart
V.
author
Wright
A.F.
author
Zemunik
T.
author
Boban
M.
author
Kolcic
I.
author
Navarro
P.
author
Brown
E.M.
author
Estrada
K.
author
Ding
J.
author
Harris
T.B.
author
Bandinelli
S.
author
Hernandez
D.
author
Singleton
A.B.
author
Girotto
G.
author
Ruggiero
D.
author
d'Adamo
A.P.
author
Robino
A.
author
Meitinger
T.
author
Meisinger
C.
author
Davies
G.
author
Starr
J.M.
author
Chambers
J.C.
author
Boehm
B.O.
author
Winkelmann
B.R.
author
Huang
J.
author
Murgia
F.
author
Wild
S.H.
author
Campbell
H.
author
Morris
A.P.
author
Franco
O.H.
author
Hofman
A.
author
Uitterlinden
A.G.
author
Rivadeneira
F.
author
Völker
U.
author
Hannemann
A.
author
Biffar
R.
author
Hoffmann
W.
author
Shin
S.Y.
author
Lescuyer
P.
author
Henry
H.
author
Schurmann
C.
author
SUNLIGHT Consortium
contributor
GEFOS Consortium
contributor
Munroe
P.B.
author
Munroe
P.B.
author
Gasparini
P.
author
Pirastu
N.
author
Ciullo
M.
author
Gieger
C.
author
März
W.
author
Lind
L.
author
Spector
T.D.
author
Smith
A.V.
author
Rudan
I.
author
Wilson
J.F.
author
Polasek
O.
author
Deary
I.J.
author
Pirastu
M.
author
Ferrucci
L.
author
Liu
Y.
author
Kestenbaum
B.
author
Kooner
J.S.
author
Witteman
J.C.
author
Nauck
M.
author
Kao
W.H.
author
Wallaschofski
H.
author
Bonny
O.
author
Fox
C.S.
author
Bochud
M.
author
article
2013
Plos Genetics
1553-7404
1553-7390
journal
9
9
e1003796
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.
eng
60_published
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University of Lausanne
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