DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Bone mineral density. The EFO term bone density was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: bone density

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

EL Duncan, P Danoy, JP Kemp, PJ Leo, E McCloskey, GC Nicholson, R Eastell, RL Prince, JA Eisman, G Jones, PN Sambrook, IR Reid, EM Dennison, J Wark, JB Richards, AG Uitterlinden, TD Spector, C Esapa, RD Cox, SD Brown, RV Thakker, KA Addison, LA Bradbury, JR Center, C Cooper, C Cremin, K Estrada, D Felsenberg, CC Glüer, J Hadler, MJ Henry, A Hofman, MA Kotowicz, J Makovey, SC Nguyen, TV Nguyen, JA Pasco, K Pryce, DM Reid, F Rivadeneira, C Roux, K Stefansson, U Styrkarsdottir, G Thorleifsson, R Tichawangana, DM Evans, MA Brown

TITLE:

Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk.

JOURNAL:

PLoS genetics Apr 2011, Vol 7, pp. e1001372

ABSTRACT:

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies. PUBMED: 21533022
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