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

Autoria(s): O'Seaghdha C.M.; Wu H.; Yang Q.; Kapur K.; Guessous I.; Zuber A.M.; Köttgen A.; Stoudmann C.; Teumer A.; Kutalik Z.; Mangino M.; Dehghan A.; Zhang W.; Eiriksdottir G.; Li G.; Tanaka T.; Portas L.; Lopez L.M.; Hayward C.; Lohman K.; Matsuda K.; Padmanabhan S.; Firsov D.; Sorice R.; Ulivi S.; Brockhaus A.C.; Kleber M.E.; Mahajan A.; Ernst F.D.; Gudnason V.; Launer L.J.; Mace A.; Boerwinckle E.; Arking D.E.; Tanikawa C.; Nakamura Y.; Brown M.J.; Gaspoz J.M.; Theler J.M.; Siscovick D.S.; Psaty B.M.; Bergmann S.; Vollenweider P.; Vitart V.; Wright A.F.; Zemunik T.; Boban M.; Kolcic I.; Navarro P.; Brown E.M.; Estrada K.; Ding J.; Harris T.B.; Bandinelli S.; Hernandez D.; Singleton A.B.; Girotto G.; Ruggiero D.; d'Adamo A.P.; Robino A.; Meitinger T.; Meisinger C.; Davies G.; Starr J.M.; Chambers J.C.; Boehm B.O.; Winkelmann B.R.; Huang J.; Murgia F.; Wild S.H.; Campbell H.; Morris A.P.; Franco O.H.; Hofman A.; Uitterlinden A.G.; Rivadeneira F.; Völker U.; Hannemann A.; Biffar R.; Hoffmann W.; Shin S.Y.; Lescuyer P.; Henry H.; Schurmann C.; SUNLIGHT Consortium; GEFOS Consortium; Munroe P.B.; Munroe P.B.; Gasparini P.; Pirastu N.; Ciullo M.; Gieger C.; März W.; Lind L.; Spector T.D.; Smith A.V.; Rudan I.; Wilson J.F.; Polasek O.; Deary I.J.; Pirastu M.; Ferrucci L.; Liu Y.; Kestenbaum B.; Kooner J.S.; Witteman J.C.; Nauck M.; Kao W.H.; Wallaschofski H.; Bonny O.; Fox C.S.; Bochud M.
Data(s)

2013
Resumo

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.
Identificador

http://serval.unil.ch/?id=serval:BIB_2AD446B425B4

isbn:1553-7404 (Electronic)

pmid:24068962

doi:10.1371/journal.pgen.1003796

isiid:000325076600054

http://my.unil.ch/serval/document/BIB_2AD446B425B4.pdf

http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_2AD446B425B42
Idioma(s)

en
Direitos

info:eu-repo/semantics/openAccess
Fonte

Plos Genetics, vol. 9, no. 9, pp. e1003796
Tipo

info:eu-repo/semantics/article

article
Acesso ao item digital