Genome-wide association study identifies novel susceptible loci and highlights Wnt/beta-catenin pathway in the development of adolescent idiopathic scoliosis

• Published in: Human molecular genetics Vol. 26; no. 8; pp. 1577 - 1583
• Main Authors: Zhu, Zezhang, Xu, Leilei, Leung-Sang Tang, Nelson, Qin, Xiaodong, Feng, Zhenhua, Sun, Weixiang, Zhu, Weiguo, Shi, Benlong, Liu, Peng, Mao, Saihu, Qiao, Jun, Liu, Zhen, Sun, Xu, Li, Fangcai, Chun-Yiu Cheng, Jack, Qiu, Yong
• Format: Journal Article
• Language: English
• Published: England 15.04.2017
• Subjects: Adolescent; beta Catenin - biosynthesis; beta Catenin - genetics; Cell Adhesion Molecules, Neuronal - genetics; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Germinal Center Kinases; Homeodomain Proteins - biosynthesis; Homeodomain Proteins - genetics; Humans; Male; Myeloid Ecotropic Viral Integration Site 1 Protein; Neoplasm Proteins - genetics; Polymorphism, Single Nucleotide; Protein-Serine-Threonine Kinases - genetics; Scoliosis - genetics; Scoliosis - pathology; Transcription Factors - biosynthesis; Wnt Signaling Pathway
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddx045

The genetic architecture of adolescent idiopathic scoliosis (AIS) remains poorly understood. Here we present the result of a 4-stage genome-wide association study composed of 5,953 AIS patients and 8,137 controls. Overall, we identified three novel susceptible loci including rs7593846 at 2p14 near MEIS1 (Pcombined = 1.19 × 10-13, OR = 1.21, 95% CI = 1.10-1.32), rs7633294 at 3p14.1 near MAGI1 (Pcombined = 1.85 × 10-12, OR = 1.20, 95% CI = 1.09-1.32), and rs9810566 at 3q26.2 near TNIK (Pcombined = 1.14 × 10-11, OR = 1.19, 95% CI = 1.08-1.32). We also confirmed a recently reported region associated with AIS at 20p11.22 (Pcombined = 1.61 × 10-15, OR = 1.22, 95% CI = 1.12-1.34). Furthermore, we observed significantly asymmetric expression of Wnt/beta-catenin pathway in the bilateral paraspinal muscle of AIS patients, including beta-catenin, TNIK, and LBX1. This is the first study that unveils the potential role of Wnt/beta-catenin pathway in the development of AIS, and our findings may shed new light on the etiopathogenesis of AIS.