Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density

Alonso, Nerea, Estrada, Karol, Albagha, Omar M. E., Herrera, Lizbeth, Reppe, Sjur, Olstad, Ole K., Gautvik, Kaare M., Ryan, Niamh M., Evans, Kathryn L., Nielson, Carrie M., Hsu, Yi-Hsiang, Kiel, Douglas P., Markozannes, George, Ntzani, Evangelia E, Evangelou, Evangelos, Feenstra, Bjarke, Liu, Xueping, Melbye, Mads, Masi, Laura, Brandi, Maria Luisa, Riches, Philip, Daroszewska, Anna, Olmos, José Manuel, Valero, Carmen, Castillo, Jesús, Riancho, José A., Husted, Lise B., Langdahl, Bente L., Brown, Matthew A., Duncan, Emma L., Kaptoge, Stephen, Khaw, Kay-Tee, Usategui-Martín, Ricardo, Del Pino-Montes, Javier, González-Sarmiento, Rogelio, Lewis, Joshua R., Prince, Richard L., D'Amelio, Patrizia, García-Giralt, Natalia, Nogués, Xavier, Mencej-Bedrac, Simona, Marc, Janja, Wolstein, Orit, Eisman, John A., Oei, Ling, Medina-Gómez, Carolina, Schraut, Katharina E., Navarro, Pau, Wilson, James F., Davies, Gail, Starr, John, Deary, Ian, Tanaka, Toshiko, Ferrucci, Luigi, Gianfrancesco, Fernando, Gennari, Luigi, Lucas, Gavin, Elosua, Roberto, Uitterlinden, André G, Rivadeneira, Fernando and Ralston, Stuart H. (2017) Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density. Annals of Rheumatic Diseases, 77 3: 378-385. doi:10.1136/annrheumdis-2017-212469

Author Alonso, Nerea
Estrada, Karol
Albagha, Omar M. E.
Herrera, Lizbeth
Reppe, Sjur
Olstad, Ole K.
Gautvik, Kaare M.
Ryan, Niamh M.
Evans, Kathryn L.
Nielson, Carrie M.
Hsu, Yi-Hsiang
Kiel, Douglas P.
Markozannes, George
Ntzani, Evangelia E
Evangelou, Evangelos
Feenstra, Bjarke
Liu, Xueping
Melbye, Mads
Masi, Laura
Brandi, Maria Luisa
Riches, Philip
Daroszewska, Anna
Olmos, José Manuel
Valero, Carmen
Castillo, Jesús
Riancho, José A.
Husted, Lise B.
Langdahl, Bente L.
Brown, Matthew A.
Duncan, Emma L.
Kaptoge, Stephen
Khaw, Kay-Tee
Usategui-Martín, Ricardo
Del Pino-Montes, Javier
González-Sarmiento, Rogelio
Lewis, Joshua R.
Prince, Richard L.
D'Amelio, Patrizia
García-Giralt, Natalia
Nogués, Xavier
Mencej-Bedrac, Simona
Marc, Janja
Wolstein, Orit
Eisman, John A.
Oei, Ling
Medina-Gómez, Carolina
Schraut, Katharina E.
Navarro, Pau
Wilson, James F.
Davies, Gail
Starr, John
Deary, Ian
Tanaka, Toshiko
Ferrucci, Luigi
Gianfrancesco, Fernando
Gennari, Luigi
Lucas, Gavin
Elosua, Roberto
Uitterlinden, André G
Rivadeneira, Fernando
Ralston, Stuart H.
Title Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density
Journal name Annals of Rheumatic Diseases   Check publisher's open access policy
ISSN 1468-2060
Publication date 2017-11-23
Year available 2017
Sub-type Article (original research)
DOI 10.1136/annrheumdis-2017-212469
Open Access Status Not yet assessed
Volume 77
Issue 3
Start page 378
End page 385
Total pages 8
Place of publication London, United Kingdom
Publisher B M J Group
Language eng
Abstract To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis.

Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies.

A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10-9) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures.

We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism.
Keyword bone mineral density
gene polymorphism
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Faculty of Medicine
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Created: Wed, 29 Nov 2017, 12:00:58 EST