In an effort to discover the genetic basis of bone size in the spine, a factor known to contribute to the risk of spinal fracture in patients with osteoporosis, Deng et al. performed a genome-wide association study (GWAS) in 2286 Caucasian subjects.1 These unrelated individuals were assessed by dual energy X-ray absorptiometry to determine the areal bone size in cm2 within their lumbar spine.
A total of 91 single nucleotide polymorphisms (SNPs) were initially pinpointed by the GWAS, eight of them clustered within the ubiquinol-cytochrome c reductase complex chaperone gene (UQCC). In a replication study performed in three independent populations (1000 Caucasians, 2503 Caucasians and 1627 Chinese), all eight SNPs within UQCC were replicated in the larger Caucasian population and in the Chinese population.
UQCC therefore appears to be a novel genomic locus associated with spinal bone-size variation. The role of UQCC in bone is not yet known, but the gene encoding growth/differentiation factor 5 (GDF5), which is highly relevant to bone biology, lies very close to the UQCC locus.
Editor's comment: Several previous GWAS have reported that common variants in the GDF5-UQCC locus contribute to variation of height. Additionally, a GWAS meta-analysis evaluated the contribution of height loci to the skeletal components of height and found UQCC to be associated with hip-axis length.2 The findings of this current study therefore make perfect sense, since adult height is a function of both upper- and lower-body size.
References
- Deng FY, Dong SS, Xu XH, Liu YJ, Liu YZ, Shen H et al. Genome-wide association study identified UQCC locus for spine bone size in humans. Bone 2013;53:129–133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soranzo N, Rivadeneira F, Chinappen-Horsley U, Malkina I, Richards JB, Hammond N et al. Meta-analysis of genome-wide scans for human adult stature identifies novel loci and associations with measures of skeletal frame size. PLoS Genet 2009;5:e1000445. [DOI] [PMC free article] [PubMed] [Google Scholar]
