Genome-wide association study identifies two novel loci containing FLNB and SBF2 genes underlying stature variation
Genome-wide association study identifies two novel loci containing FLNB and SBF2 genes underlying stature variation
复制标题
全基因组关联研究确定了两个包含 FLNB 和 SBF2 基因的新位点，这些基因可能导致身材变异
DOI：
10.1093/hmg/ddn405
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发表时间：
2009-05-01
影响因子：
3.5
通讯作者：
Deng, Hong-Wen
中科院分区：
文献类型：
--
作者：
Lei, Shu-Feng;Tan, Li-Jun;Deng, Hong-Wen
身高是一种高度遗传的复杂性状，是临床实践中的一项重要体格指标，也是复杂疾病基因定位中的一个常用协变量。为了确定特定的基因潜在的身高，全基因组关联研究进行了1000无关的同质高加索受试者使用Affytron 500 K阵列。SBF 2基因（Set-结合因子2）区域的一组7个连续标记与身高相关，在错误发现率（FDR）校正后（FDR q = 0.034-0.042）在全基因组水平上显著相关。细丝蛋白B（FLNB）基因中另一个SNP组中的三个SNP也与身高相关，与FDR q = 0.042-0.048显著相关。在后续的独立复制研究中，SBF 2基因中的rs 10734652显著高于对照组。（P = 0.036），（P = 0.07）分别与高加索家族和1306例无关高加索受试者的身高相关，FLNB基因的rs 9834312也与两个独立的高加索人群的身高相关（无关样本P = 0.008，家系样本P = 0.049）。特别是，在中国人（不同于高加索人的种族群体）中检测到rs 9834312与619名不相关的北方中国受试者的身高之间（P = 0.017）以及rs 10734652与2953名不相关的南方中国受试者的身高之间（P = 0.048）的额外显著复制关联信号。这项研究也为一些已经发表的身高基因座提供了额外的复制证据。这些结果，连同已知的SBF 2和FLNB基因的骨骼线性生长和骨形成的功能相关性，支持FLNB和SBF 2基因的两个区域是两个新的基因座潜在的身高变化。
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.