In the first linkage study on LDD, a common musculoskeletal disorder, a genome-wide scan was performed on 14 Finnish families. The analysis resulted in identification of a putative susceptibility locus for the disease on chromosome 21.
Introduction: Lumbar disc disease (LDD) is a common musculoskeletal disorder that affects approximately 5% of the adult population. Several predisposing genetic and environmental risk factors have been identified for symptomatic LDD (i.e., symptomatic disc herniation and/or sciatic pain), but thus far, no common cause has been identified.
Materials and methods: Medical history data were collected from 186 members of 14 Finnish families with LDD.
Results: A genome-wide scan resulted in 10 chromosomal regions providing LOD scores >1, and in fine mapping, maximum two-point LOD scores of 2.71, 2.36, and 2.04 were obtained for chromosomes 21 (D21S1257), 4 (D4S399), and 6 (D6S294), respectively. A second fine mapping confirmed the susceptibility of chromosome 21 with a two-point LOD score of 2.06 (D21S1922). In addition, a significant association between LDD and SNP rs716195 was observed (p<0.001), and case-control analysis revealed pointwise significant differences with several markers. Interestingly, the locus for another spinal disorder, ossification of the posterior longitudinal ligament (OPLL), has been mapped to chromosome 21q, partially overlapping with our candidate region. Two candidate genes with aggrecanase activity, ADAMTS-1 and ADAMTS-5, were analyzed in the region, suggesting linkage, leading to the identification of 13 sequence variations. None of the variations were disease-causing, however, because they were observed equally in affected and healthy individuals.
Conclusions: We report here on the first putative susceptibility locus for LDD in the Finnish population. The candidate region on chromosome 21q spans >5.5 cM and contains several interesting genes for further analysis.