A genomic screen and statistical linkage analysis of 202 families with at least two individuals with idiopathic scoliosis was performed. To identify candidate regions or the autosomal loci that may be involved in the expression of familial idiopathic scoliosis. A large sample of families with individuals having idiopathic scoliosis (202 families; 1,198 individuals) was ascertained; diagnoses were based on physical examination and radiographic criteria. Model-independent linkage analysis of qualitative and quantitative traits (degree of lateral curvature) related to scoliosis was used to screen genotyping data from 391 markers in the 202 families. Subsets of families were determined before genotyping based on the most likely mode of inheritance for each family (autosomal dominant vs. X-linked dominant). Fine mapping results corroborated linkage in the primary candidate regions. Candidate regions on chromosomes 6, 9, 16, and 17 were considered to have the strongest evidence for linkage across all subsets considered. Linkage analyses have identified several candidate regions, a significant step in defining the genetic etiology of this disorder.

Study Design. We performed genomic screening, statistical linkage analysis, and fine mapping of 202 families with at least 2 individuals with idiopathic scoliosis. Objective. To identify regions on chromosome 19p13 statistically linked to the phenotypic expression of idiopathic scoliosis. Summary of Background Data. Idiopathic scoliosis is a common structural curvature of the spine affecting otherwise healthy children. Presently, no clear consensus exists regarding the underlying abnormality or genetic determinants of this disease. Methods. Model-independent linkage analysis of qualitative and quantitative traits related to scoliosis was used to screen genotyping data from 391 markers in 202 families (1198 individuals). Subsets of families with probands having a curve ≥30° were dichotomized based on the most likely mode of inheritance for each family (autosomal dominant or X-linked dominant). Fine mapping was performed to show linkage to candidate regions on chromosome 19. Results. When the threshold of disease was set at a curvature of ≥30°, qualitative linkage analysis revealed significant results at 2 successive markers on chromosome 19. Conclusion. The data confirm a previously reported genetic locus on chromosome 19 as potentially significant in the etiology of idiopathic scoliosis.