Human Molecular Genetics Advance Access originally published online on November 27, 2008
Human Molecular Genetics 2009 18(9):1661-1669; doi:10.1093/hmg/ddn405
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Genome-wide association study identifies two novel loci containing FLNB and SBF2 genes underlying stature variation
1 Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, PR China 2 School of Medicine, University of Missouri - Kansas City, Kansas City, MO 64108, USA 3 The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shanxi 710049, PR China 4 Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA 5 Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
* To whom correspondence should be addressed. Email: dengh{at}umkc.edu
Received August 10, 2008; Accepted November 26, 2008
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.