RT Journal Article
SR Electronic
T1 Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP annrheumdis-2017-212469
DO 10.1136/annrheumdis-2017-212469
A1 Nerea Alonso
A1 Karol Estrada
A1 Omar M E Albagha
A1 Lizbeth Herrera
A1 Sjur Reppe
A1 Ole K Olstad
A1 Kaare M Gautvik
A1 Niamh M Ryan
A1 Kathryn L Evans
A1 Carrie M Nielson
A1 Yi-Hsiang Hsu
A1 Douglas P Kiel
A1 George Markozannes
A1 Evangelia E Ntzani
A1 Evangelos Evangelou
A1 Bjarke Feenstra
A1 Xueping Liu
A1 Mads Melbye
A1 Laura Masi
A1 Maria Luisa Brandi
A1 Philip Riches
A1 Anna Daroszewska
A1 José Manuel Olmos
A1 Carmen Valero
A1 Jesús Castillo
A1 José A Riancho
A1 Lise B Husted
A1 Bente L Langdahl
A1 Matthew A Brown
A1 Emma L Duncan
A1 Stephen Kaptoge
A1 Kay-Tee Khaw
A1 Ricardo Usategui-Martín
A1 Javier Del Pino-Montes
A1 Rogelio González-Sarmiento
A1 Joshua R Lewis
A1 Richard L Prince
A1 Patrizia D’Amelio
A1 Natalia García-Giralt
A1 Xavier Nogués
A1 Simona Mencej-Bedrac
A1 Janja Marc
A1 Orit Wolstein
A1 John A Eisman
A1 Ling Oei
A1 Carolina Medina-Gómez
A1 Katharina E Schraut
A1 Pau Navarro
A1 James F Wilson
A1 Gail Davies
A1 John Starr
A1 Ian Deary
A1 Toshiko Tanaka
A1 Luigi Ferrucci
A1 Fernando Gianfrancesco
A1 Luigi Gennari
A1 Gavin Lucas
A1 Roberto Elosua
A1 André G Uitterlinden
A1 Fernando Rivadeneira
A1 Stuart H Ralston
YR 2017
UL http://ard.bmj.com/content/early/2017/11/23/annrheumdis-2017-212469.abstract
AB Objectives To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis.Methods 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.Results 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.Conclusion 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.