Genome-wide copy number variation study and gene expression analysis identify ABI3BP as a susceptibility gene for Kashin-Beck disease.
Kashin-Beck disease (KBD) is a chronic osteochondropathy. In this study, we conducted the first genome-wide copy number variation study (GCNVS) of KBD totally involving 2,743 Chinese Han adults. GCNVS was first performed using Affymetrix Human SNP6.0 Arrays. The identified copy number variations (CNVs) were then replicated in an independent Chinese Han sample containing 1,026 subjects. SNP genotyping, CNV identification and quality control were implemented by Birdsuite. STRUCTURE and EIGENSTRAT were applied for controlling potential population stratification in the GCNVS. Association analysis was conducted using PLINK. Microarray and qRT-PCR were also conducted to compare the expression levels of the genes overlapping with identified CNVs between KBD patients and healthy controls. GCNVS found that CNV452 (P value = 7.78 × 10(-5)) overlapping with ABI3BP gene was significantly associated with KBD. Replication association study observed that rs9850273 (P value = 0.008) and rs7613610 (P value = 0.021) in ABI3BP gene were significantly associated with KBD. Gene expression analysis also found that ABI3BP was up-regulated in KBD patients compared to healthy controls. Our results suggest that ABI3BP was a novel susceptibility gene for KBD.
Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Faculty of Public Health, College of Medicine, Xi'an Jiaotong University, Xi'an, People's Republic of China, fzhxjtu@mail.xjtu.edu.cn.
Feng
F
Zhang
Xiong
X
Guo
Yinping
Y
Zhang
Yan
Y
Wen
Weizhuo
W
Wang
Sen
S
Wang
Tielin
T
Yang
Hui
H
Shen
Xiangding
X
Chen
Qing
Q
Tian
Lijun
L
Tan
Hong-Wen
HW
Deng
D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D057767:Kashin-Beck Disease / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C439569:ABI3BP protein, human; D002352:Carrier Proteins