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

THRESHOLD:

<= 0.05

GENES IN THRESHOLD:

1

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-10-22

SPECIES:

AUTHORS:

AW Kung, SM Xiao, S Cherny, GH Li, Y Gao, G Tso, KS Lau, KD Luk, JM Liu, B Cui, MJ Zhang, ZL Zhang, JW He, H Yue, WB Xia, LM Luo, SL He, DP Kiel, D Karasik, YH Hsu, LA Cupples, S Demissie, U Styrkarsdottir, BV Halldorsson, G Sigurdsson, U Thorsteinsdottir, K Stefansson, JB Richards, G Zhai, N Soranzo, A Valdes, TD Spector, PC Sham

TITLE:

Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies.

JOURNAL:

American journal of human genetics Feb 2010, Vol 86, pp. 229-39

ABSTRACT:

Bone mineral density (BMD), a diagnostic parameter for osteoporosis and a clinical predictor of fracture, is a polygenic trait with high heritability. To identify genetic variants that influence BMD in different ethnic groups, we performed a genome-wide association study (GWAS) on 800 unrelated Southern Chinese women with extreme BMD and carried out follow-up replication studies in six independent study populations of European descent and Asian populations including 18,098 subjects. In the meta-analysis, rs2273061 of the Jagged1 (JAG1) gene was associated with high BMD (p = 5.27 x 10(-8) for lumbar spine [LS] and p = 4.15 x 10(-5) for femoral neck [FN], n = 18,898). This SNP was further found to be associated with the low risk of osteoporotic fracture (p = 0.009, OR = 0.7, 95% CI 0.57-0.93, n = 1881). Region-wide and haplotype analysis showed that the strongest association evidence was from the linkage disequilibrium block 5, which included rs2273061 of the JAG1 gene (p = 8.52 x 10(-9) for LS and 3.47 x 10(-5) at FN). To assess the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of c-Myc to the "G" but not "A" allele of rs2273061. A mRNA expression study in both human bone-derived cells and peripheral blood mononuclear cells confirmed association of the high BMD-related allele G of rs2273061 with higher JAG1 expression. Our results identify the JAG1 gene as a candidate for BMD regulation in different ethnic groups, and it is a potential key factor for fracture pathogenesis. PUBMED: 20096396
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