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

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.; 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.

doi:10.1371/journal.pgen.1003796

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

Détails

Télécharger: BIB_2AD446B425B4.P001.pdf (797.02 [Ko])
Etat: Public
Version: de l'auteur⸱e

ID Serval

serval:BIB_2AD446B425B4

Type

Article: article d'un périodique ou d'un magazine.

Collection

Publications

Institution

UNIL/CHUV

Titre

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

Périodique

Plos Genetics

Auteur⸱e⸱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., 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.

Collaborateur⸱rice⸱s

SUNLIGHT Consortium, GEFOS Consortium

ISSN

1553-7404 (Electronic)

ISSN-L

1553-7390

Statut éditorial

Publié

Date de publication

2013

Volume

Numéro

Pages

e1003796

Langue

anglais

Résumé

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.

URN

urn:nbn:ch:serval-BIB_2AD446B425B42

OAI-PMH

oai:serval.unil.ch:BIB_2AD446B425B4

DOI

10.1371/journal.pgen.1003796

Pubmed

24068962

Web of science

000325076600054

Open Access

Oui