A joint research group from Fujita Health University and Keio University has revealed, through both clinical data and genetic analysis, that "family history" and "late age of menarche" may be involved in the progression of adolescent idiopathic scoliosis (AIS).
AIS is a disorder of unknown cause that primarily affects girls after the age of 10, causing three-dimensional twisting of the spine and resulting in trunk deformities. In severe cases, it can cause not only visible deformities but also lower back pain and respiratory dysfunction, and is estimated to affect 2-3% of the adolescent population.
Previous studies have suggested that family history (number of blood relatives with the same disease) and late age of menarche are associated with the Cobb angle, which indicates the severity of scoliosis. Therefore, in this study, we combined clinical data and genetic statistical analysis from approximately 5,900 AIS patients to examine these relationships from both clinical and genetic perspectives.
The results showed that patients with a family history had a significantly larger Cobb angle, and a dose-dependent association was found where the severity of scoliosis increased with the number of affected relatives. A linear association was also observed where the later the age of menarche, the more severe the scoliosis. When the patients were divided into three groups based on the age of menarche, the Cobb angle was approximately 7 degrees larger on average in the group with the latest age of menarche compared to the group with the earliest age.
When these clinical associations were investigated using large-scale genomic data, Mendelian randomization, which estimates genetic causality, genetically confirmed that a predisposition to late menarche (genetic effect) may causally contribute to the severity of scoliosis. Furthermore, it was revealed that genetic factors related to menarche age did not correlate with the "susceptibility" to developing AIS, but were specifically related to its "severity."
Since family history and age of menarche can be easily obtained through interviews, the results of this study may be useful for "stratifying the risk of severe illness," which allows for the early identification of patients who are more likely to develop severe illness. In the future, it is hoped that elucidating the biological mechanisms linking late age of menarche to the severity of illness will lead to the development of new treatments and preventive measures to suppress severe illness.
