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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 ofSBF2gene (Set-binding factor 2) are associated with stature, significantly so at the genome-wide level after false discovery rate (FDR) correction (FDRq= 0.034–0.042). Three SNPs in another SNP group in the Filamin B (FLNB) gene were also associated with stature, significantly so with FDRq= 0.042–0.048. In follow-up independent replication studies, rs10734652 in theSBF2gene 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 theFLNBgene was also associated with stature in such two independent Caucasian populations (P= 0.008 in unrelated sample andP= 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 theSBF2andFLNBgenes to skeletal linear growth and bone formation, support that two regions containingFLNBandSBF2genes are two novel loci underlying stature variation.

human molecular genetics

Genome-wide association study identifies two novel loci containing               FLNB               and               SBF2               genes underlying stature variation