PT  - JOURNAL ARTICLE
AU  - Nerea Alonso
AU  - Karol Estrada
AU  - Omar M E Albagha
AU  - Lizbeth Herrera
AU  - Sjur Reppe
AU  - Ole K Olstad
AU  - Kaare M Gautvik
AU  - Niamh M Ryan
AU  - Kathryn L Evans
AU  - Carrie M Nielson
AU  - Yi-Hsiang Hsu
AU  - Douglas P Kiel
AU  - George Markozannes
AU  - Evangelia E Ntzani
AU  - Evangelos Evangelou
AU  - Bjarke Feenstra
AU  - Xueping Liu
AU  - Mads Melbye
AU  - Laura Masi
AU  - Maria Luisa Brandi
AU  - Philip Riches
AU  - Anna Daroszewska
AU  - José Manuel Olmos
AU  - Carmen Valero
AU  - Jesús Castillo
AU  - José A Riancho
AU  - Lise B Husted
AU  - Bente L Langdahl
AU  - Matthew A Brown
AU  - Emma L Duncan
AU  - Stephen Kaptoge
AU  - Kay-Tee Khaw
AU  - Ricardo Usategui-Martín
AU  - Javier Del Pino-Montes
AU  - Rogelio González-Sarmiento
AU  - Joshua R Lewis
AU  - Richard L Prince
AU  - Patrizia D’Amelio
AU  - Natalia García-Giralt
AU  - Xavier Nogués
AU  - Simona Mencej-Bedrac
AU  - Janja Marc
AU  - Orit Wolstein
AU  - John A Eisman
AU  - Ling Oei
AU  - Carolina Medina-Gómez
AU  - Katharina E Schraut
AU  - Pau Navarro
AU  - James F Wilson
AU  - Gail Davies
AU  - John Starr
AU  - Ian Deary
AU  - Toshiko Tanaka
AU  - Luigi Ferrucci
AU  - Fernando Gianfrancesco
AU  - Luigi Gennari
AU  - Gavin Lucas
AU  - Roberto Elosua
AU  - André G Uitterlinden
AU  - Fernando Rivadeneira
AU  - Stuart H Ralston
TI  - Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density
AID  - 10.1136/annrheumdis-2017-212469
DP  - 2017 Nov 23
TA  - Annals of the Rheumatic Diseases
PG  - annrheumdis-2017-212469
4099  - http://ard.bmj.com/content/early/2017/11/23/annrheumdis-2017-212469.short
4100  - http://ard.bmj.com/content/early/2017/11/23/annrheumdis-2017-212469.full
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.