Genome-wide association study identifies two novel loci containing FLNB and SBF2 genes underlying stature variation.
Human stature, as an important physical index in clinical practice and a usual covariate in gene mapping of complex disorders, is a highly heritable complex trait. To identify specific genes underlying stature, a genome-wide association study was performed in 1000 unrelated homogeneous Caucasian subjects using Affymetrix 500K arrays. A group of seven contiguous markers in the region of SBF2 gene (Set-binding factor 2) are associated with stature, significantly so at the genome-wide level after false discovery rate (FDR) correction (FDR q = 0.034-0.042). Three SNPs in another SNP group in the Filamin B (FLNB) gene were also associated with stature, significantly so with FDR q = 0.042-0.048. In follow-up independent replication studies, rs10734652 in the SBF2 gene was significantly (P = 0.036) and suggestively (P = 0.07) associated with stature in Caucasian families and 1306 unrelated Caucasian subjects, respectively, and rs9834312 in the FLNB gene was also associated with stature in such two independent Caucasian populations (P = 0.008 in unrelated sample and P = 0.049 in family sample). Particularly, additional significant replication association signals were detected in Chinese, an ethnic population different from Caucasian, between rs9834312 and stature in 619 unrelated northern Chinese subjects (P = 0.017), as well as between rs10734652 and stature in 2953 unrelated southern Chinese subjects (P = 0.048). This study also provides additional replication evidence for some of the already published stature loci. These results, together with the known functional relevance of the SBF2 and FLNB genes to skeletal linear growth and bone formation, support that two regions containing FLNB and SBF2 genes are two novel loci underlying stature variation.
Lei
Shu-Feng
SF
Hunan Normal University, Changsha, PR China.
Tan
Li-Jun
LJ
Liu
Xiao-Gang
XG
Wang
Liang
L
Yan
Han
H
Guo
Yan-Fang
YF
Liu
Yao-Zhong
YZ
Xiong
Dong-Hai
DH
Li
Jian
J
Yang
Tie-Lin
TL
Chen
Xiang-Ding
XD
Guo
Yan
Y
Deng
Fei-Yan
FY
Zhang
Yin-Ping
YP
Zhu
Xue-Zhen
XZ
Levy
Shawn
S
Papasian
Christopher J
CJ
Hamilton
James J
JJ
Recker
Robert R
RR
Deng
Hong-Wen
HW
D000328:Adult; D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D001827:Body Height; D003285:Contractile Proteins / Q000235:genetics*; D005260:Female; D064448:Filamins; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics*; D044465:White People / Q000235:genetics
D003285:Contractile Proteins; C578662:FLNB protein, human; D064448:Filamins; D008840:Microfilament Proteins; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C475072:SBF2 protein, human