IBMS BoneKEy | BoneKEy Watch
Zhou et al. Predicting genetic risk of femoral fracture: A novel genetic risk score
DOI:10.1038/bonekey.2016.34
Zhou et al. report the development of a novel genetic risk score (GRS) useful for predicting fracture risk. The GRS is based on data on the lifetime risk of hip fractures in Japanese subjects (924 and 708 consecutive autopsies in men and women respectively). GRS values were calculated as the sum of risk allele counts (unweighted GRS) or the sum of weighted scores from logistic regression coefficients (weighted GRS).
The association between femoral fractures and a total of 922 single nucleotide polymorphisms (SNPs) located in exons of 62 genotyped osteoporosis susceptibility genes was assessed. Among 922 SNPs, four (IDUA rs3755955, C7orf58 rs190543052, homeobox (HOX)C4 rs75256744, and G patch domain-containing gene (GPATCH)1 rs2287679 and Werner syndrome rs2230009) were significantly associated with the prevalence of femoral fracture in male autopsy cases. The Werner syndrome gene has previously been associated with femoral fracture risk. Only one SNP showed a significant association in females ((IDUA rs3755955).
Editor’s comment: It should be noted that most of the 922 SNPs are not identical to the originally reported GEFOS SNPs, which were located in non-coding regions. Non-synonymous SNPs were genotyped here in order to identify ‘functional’ polymorphisms. This GWAS in East Asian ancestry is an important contribution to our knowledge in this field but the difference in age between the cases and controls (half decade) is concerning.
This work is licensed under a
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.