Polygenic inheritance of adolescent idiopathic scoliosis: a study of extended families in Utah.

摘要

A heritability study of 69 extended Utah families with a history of adolescent idiopathic scoliosis (AIS) indicates that AIS is a polygenic, multifactorial condition. Each family reported a history of AIS within four generations; a total of 247 individuals were confirmed via X-rays and medical records to have AIS. Coefficient of kinship was more than 25 standard deviations higher for these 69 families than for the general population. Excluding all probands and assuming autosomal dominant inheritance, 1,260 individuals over the age of 16 were determined to be at risk for AIS because they have a parent with AIS. Assuming 50% of these individuals carry the allele, estimated penetrance in at-risk males is approximately 9%, and estimated penetrance in at-risk females is approximately 29%. Recurrence risk in relatives decreases as the degree of relationship to the affected individual becomes more distant; however, the lowest recurrence risk calculated, for third-degree relatives, is still an average of 9%, well above the general population's risk. Onset of AIS appears to be inherited separate from curve pattern and severity. In a study of phenotypes in 36 of the families, the affected individuals were consistent in either curve severity or curve pattern, but not both. It is unclear whether severity or pattern is more heritable, but it is possible that the location of the curve on the spine is the most heritable trait of the phenotype. The study demonstrates the genetic complexity of AIS, including the low penetrance of its cumulative alleles and variable expression.