Adolescent Idiopathic Scoliosis (AIS) 1000 Exomes Study

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Although the Bracing in AIS Trial (BrAIST) recently demonstrated the effectiveness of bracing for preventing scoliosis progression in some patients, more than 20,000 children undergo major spinal fusion surgery at an annual cost of $3 billion. Spinal fusion surgery is a major operation with considerable risks and complications. Accurate methods of predicting curve progression are needed to develop personalized prevention strategies for those at high risk and to eliminate screening and treatment of those at low risk of progression. Previously identified risk factors for scoliosis curve progression include sex, age of onset, curve type, and presence of an underlying disorder. However, currently available algorithms for predicting AIS curve progression are inaccurate, possibly because the role of genetic factors has been largely unexplored. Because there is little a priori knowledge of the genetic variants involved in AIS pathology, an unbiased genome-wide approach is likely to provide the best opportunity to comprehensively identify disease-associated genes. This is a multicenter exome sequencing study of extreme cases with severe scoliosis. ]]> The inclusion criteria for cases are unrelated Caucasian individuals with moderate or severe spinal curvature having onset in childhood or adolescence, and absence of congenital scoliosis or other known underlying disorder. ]]> This study is a collaborative effort from researchers and clinicians from multiple centers who have a long history of collaborations through BRAIST (Bracing in Adolescent Idiopathic Scoliosis Trial) and the International Consortium for Spinal Genetics, Development, and Disease. Investigators at seven study sites contributed samples: Washington University (Matthew Dobbs), Shriners Hospital for Children St Louis (Matthew Dobbs), University of Iowa (Stuart Weinstein and Jose Morcuende)(samples were not used in current study), University of Wisconsin (Phil Giampietro), Hospital for Special Surgery (Cathleen Raggio), University of Colorado (Nancy Miller), and Texas Scottish Rite Hospital (Carol Wise). ]]>