Genome-wide association study identifies novel susceptible loci and highlights Wnt/beta-catenin pathway in the development of adolescent idiopathic scoliosis.
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.
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.|Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing 210008 & Hong Kong 999077, P.R. China.
Zezhang
Z
Zhu
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.|Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing 210008 & Hong Kong 999077, P.R. China.
Leilei
L
Xu
Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing 210008 & Hong Kong 999077, P.R. China.|Department of Chemical Pathology and School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, P.R. China.|Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, P.R. China.
Nelson
N
Leung-Sang Tang
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.|Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing 210008 & Hong Kong 999077, P.R. China.
Xiaodong
X
Qin
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.|Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing 210008 & Hong Kong 999077, P.R. China.
Zhenhua
Z
Feng
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.|Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing 210008 & Hong Kong 999077, P.R. China.
Weixiang
W
Sun
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.|Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing 210008 & Hong Kong 999077, P.R. China.
Weiguo
W
Zhu
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
Benlong
B
Shi
Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun 130116, P.R. China.
Peng
P
Liu
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.|Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing 210008 & Hong Kong 999077, P.R. China.
Saihu
S
Mao
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
Jun
J
Qiao
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
Zhen
Z
Liu
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.
Xu
X
Sun
Department of Orthopaedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310002, P.R. China.
Fangcai
F
Li
Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing 210008 & Hong Kong 999077, P.R. China.|Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, P.R. China.
Jack
J
Chun-Yiu Cheng
Department of Spine Surgery, The Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.|Joint Scoliosis Research Center of The Chinese University of Hong Kong and Nanjing University, Nanjing 210008 & Hong Kong 999077, P.R. China.
Yong
Y
Qiu
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D000081410:Germinal Center Kinases; D051528:Guanylate Kinases; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012600:Scoliosis / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D000081410:Germinal Center Kinases; D018398:Homeodomain Proteins; C542809:LBX1 protein, human; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors; D051176:beta Catenin; D017346:Protein Serine-Threonine Kinases; C000631454:TNIK protein, human; D051528:Guanylate Kinases; C113338:MAGI1 protein, human