Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls

被引：104

作者：

Zhu, Zezhang ^{[1
,2
]}

Tang, Nelson Leung-Sang ^{[2
,3
,4
,5
]}

Xu, Leilei ^{[1
,2
]}

Qin, Xiaodong ^{[1
,2
]}

Mao, Saihu ^{[1
]}

Song, Yueming ^{[6
]}

Liu, Limin ^{[6
]}

Li, Fangcai ^{[7
]}

Liu, Peng ^{[8
]}

Yi, Long ^{[9
]}

Chang, Jiang ^{[10
]}

Jiang, Long ^{[11
]}

Ng, Bobby Kin-Wah ^{[12
]}

Shi, Benlong ^{[1
]}

Zhang, Wen ^{[1
]}

Qiao, Jun ^{[1
,2
]}

Sun, Xu ^{[1
,2
]}

Qiu, Xusheng ^{[1
,2
]}

Wang, Zhou ^{[1
]}

Wang, Fei ^{[1
]}

Xie, Dingding ^{[1
]}

Chen, Ling ^{[1
]}

Chen, Zhonghui ^{[1
]}

Jin, Mengran ^{[1
]}

Han, Xiao ^{[1
]}

Hu, Zongshan ^{[1
]}

Zhang, Zhen ^{[1
]}

Liu, Zhen ^{[1
]}

Zhu, Feng ^{[1
]}

Qian, Bang-ping ^{[1
,2
]}

Yu, Yang ^{[1
,2
]}

Wang, Bing ^{[1
,2
]}

Lee, K. M. ^{[5
]}

Lee, Wayne Y. W. ^{[12
]}

Lam, T. P. ^{[12
]}

Qiu, Yong ^{[1
,2
]}

Cheng, Jack Chun-Yiu ^{[2
,5
,12
]}

机构：

[1] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Spine Surg, Nanjing 210008, Peoples R China

[2] Joint Scoliosis Res Ctr Chinese Univ Hong Kong &, Nanjing 210008, Peoples R China

[3] Chinese Univ Hong Kong, Fac Med, Dept Chem Pathol, Hong Kong, Hong Kong, Peoples R China

[4] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China

[5] Chinese Univ Hong Kong, Fac Med, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China

[6] Sichuan Univ, West China Hosp, Dept Orthopaed, Chengdu 610000, Peoples R China

[7] Zhejiang Univ, Dept Orthopaed, Sch Med, Affiliated Hosp 2, Hangzhou 310000, Zhejiang, Peoples R China

[8] Jilin Univ, Dept Orthopaed, China Japan Union Hosp, Changchun 130022, Peoples R China

[9] Nanjing Univ, Sch Med, Jiangsu Key Lab Mol Med, Nanjing 210008, Peoples R China

[10] Huazhong Univ Sci & Technol, Sch Publ Hlth, Tongji Med Coll,Minist Environm Protect,Key Lab E, State Key Lab Environm Hlth Incubat,MOE,Key Lab E, Wuhan 430000, Peoples R China

[11] Yixing People Hosp, Dept Orthopaed, Wuxi 214200, Peoples R China

[12] Chinese Univ Hong Kong, Fac Med, Dept Orthopaed & Traumatol, Hong Kong, Hong Kong, Peoples R China

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

GENETIC ASSOCIATION; NATURAL-HISTORY; HAN CHINESE; DIFFERENTIATION; POPULATION; PAX3; VARIANTS; CADHERIN; COMPLEX; CELLS;

D O I：

10.1038/ncomms9355

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, P-combined = 2.95 x 10(-9)), 2q36.1 between PAX3 and EPHA4 (rs13398147, P-combined = 7.59 x 10(-13)) and 18q21.33 near BCL-2 (rs4940576, P-combined = 2.22 x 10(-12)). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, P-combined = 9.68 x 10(-37) ), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS.

引用

页数：6

共 55 条

[1] Neuromuscular Scoliosis [J].

Allam, Anand M. ;

Schwabe, Aloysia L. .

PM&R, 2013, 5 (11) :957-963

[2]

Amling M, 1998, PROCEEDINGS OF THE GERMAN SOCIETY FOR PATHOLOGY 82ND MEETING - 1998, P160

[3] Associations between matrilin-1 gene polymorphisms and adolescent idiopathic scoliosis curve patterns in a Korean population [J].

Bae, Jae Woong ;

Cho, Chang-Hyun ;

Min, Woo-Kie ;

Kim, Un-Kyung .

MOLECULAR BIOLOGY REPORTS, 2012, 39 (05) :5561-5567

[4] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[5]

Bharti S, 2004, MOL BIOL CELL, V15, P397, DOI 10.1091/mbc.E03-05-0281

[6] Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].

Birney, Ewan ;

Stamatoyannopoulos, John A. ;

Dutta, Anindya ;

Guigo, Roderic ;

Gingeras, Thomas R. ;

Margulies, Elliott H. ;

Weng, Zhiping ;

Snyder, Michael ;

Dermitzakis, Emmanouil T. ;

Stamatoyannopoulos, John A. ;

Thurman, Robert E. ;

Kuehn, Michael S. ;

Taylor, Christopher M. ;

Neph, Shane ;

Koch, Christoph M. ;

Asthana, Saurabh ;

Malhotra, Ankit ;

Adzhubei, Ivan ;

Greenbaum, Jason A. ;

Andrews, Robert M. ;

Flicek, Paul ;

Boyle, Patrick J. ;

Cao, Hua ;

Carter, Nigel P. ;

Clelland, Gayle K. ;

Davis, Sean ;

Day, Nathan ;

Dhami, Pawandeep ;

Dillon, Shane C. ;

Dorschner, Michael O. ;

Fiegler, Heike ;

Giresi, Paul G. ;

Goldy, Jeff ;

Hawrylycz, Michael ;

Haydock, Andrew ;

Humbert, Richard ;

James, Keith D. ;

Johnson, Brett E. ;

Johnson, Ericka M. ;

Frum, Tristan T. ;

Rosenzweig, Elizabeth R. ;

Karnani, Neerja ;

Lee, Kirsten ;

Lefebvre, Gregory C. ;

Navas, Patrick A. ;

Neri, Fidencio ;

Parker, Stephen C. J. ;

Sabo, Peter J. ;

Sandstrom, Richard ;

Shafer, Anthony .

NATURE, 2007, 447 (7146) :799-816

[7] The bcl-2 knockout mouse exhibits marked changes in osteoblast phenotype and collagen deposition in bone as well as a mild growth plate phenotype [J].

Boot-Handford, RP ;

Michaelidis, TM ;

Hillarby, MC ;

Zambelli, A ;

Denton, J ;

Hoyland, JA ;

Freemont, AJ ;

Grant, ME ;

Wallis, GA .

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 1998, 79 (05) :329-335

[8] The role of Pax genes in the development of tissues and organs:: Pax3 and Pax7 regulate muscle progenitor cell functions [J].

Buckingham, Margaret ;

Relaix, Frederic .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2007, 23 :645-673

[9] Promoter polymorphism of matrilin-1 gene predisposes to adolescent idiopathic scoliosis in a Chinese population [J].

Chen, Zhijun ;

Tang, Nelson L. S. ;

Cao, Xingbin ;

Qiao, Di ;

Yi, Long ;

Cheng, Jack C. Y. ;

Qiu, Yong .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2009, 17 (04) :525-532

[10] Genetic association of complex traits [J].

Cheng, Jack C. Y. ;

Tang, Nelson L. S. ;

Yeung, Hiu-Yan ;

Miller, Nancy .

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 2007, (462) :38-44

← 1 2 3 4 5 6 →