FBAT和PLINK软件计算等位基因频率和传递不平衡分析的应用研究

Application of FBAT and PLINK programs on allele frequency calculation and transmission disequilibrium test

目的研究FBAT和PLINK软件计算等位基因频率(allele frequency,Afreq)和传递不平衡分析(transmission disequilibrium test,TDT)的应用。方法对137个台湾非综合征型唇/腭裂核心家系,利用FBAT、PLINK和SPSS软件分别对核心家系和奠基者数据计算FGF19基因rs1789364的微效等位基因频率(minor allele frequency,MAF)。分别用FBAT、PLINK、SAS和SPSS软件及McNemar公式手工计算的方法,对家系数据进行TDT分析。结果FBAT软件2.0.2c版本对全部核心家系数据和奠基者数据计算的MAF不同,分别为20.8%和21.2%;FBAT软件1.7.3版本和PLINK软件对上述两种数据计算的MAF均为21.2%;SPSS软件对上述两种数据计算的MAF分别为20.8%和21.2%。FBAT软件两版本、PLINK和SAS软件与按McNemar公式手工计算的传递不平衡分析统计量等价(Z=-0.612,P=0.540);SPSS软件与McNemar校正公式的分析结果相同(χ2=0.260,P=0.610)。结论应用FBAT软件的1.7.3版本和PLINK软件计算奠基者的等位基因频率时,可以使用全部核心家系或单独奠基者的数据;用FBAT软件的2.0.2c版本时,只能用单独奠基者的数据。FBAT软件两版本和PLINK软件tdt命令的传递不平衡分析均为McNemar检验方法,PLINK软件的perm选项可提供确切概率。FBAT和PLINK软件是专门的遗传统计分析软件,可以直接利用家系数据计算等位基因频率和进行TDT等多项分析,SPSS和SAS软件的非遗传统计模块不宜作为家系资料分析的常规方法。研究者在使用相关软件和命令以前,利用公式或熟悉的软件对拟使用的软件命令进行研究,有助于避免误用,并对研究结果做出合理的解释。

Objective ： To test and confirm the type of datasets and algorithm to be used by FBAT and PLINK programs on allele frequency （Mreq） calculation and transmission disequilibrium test （TDT）. Methods： Minor allele frequency （MAF） for rs1789364 in FGF19 gene was calculated on 137 nonsyndromic cleft lip with or without cleft palate trios and founders separately by FBAT, PLINK and SPSS programs with two types of datasets. TDT was performed through FBAT, PLANK, SAS and SPSS programs, as well as algorithm of McNemar test by hand calculation. Results： The MAFs were 20. 8% and 21.2% respectively when trios and founders data were analyzed by FBAT v2.0. 2c. The MAFs were 21.2% with FBAT vl. 7.3 and PLANK. SPSS gave the MAFs as 20. 8% and 21.2% on trios and founders data respectively. Consistent results were given by two versions of FBAT program, PLINK and SAS as well as hand calculation based on algorithm of unadjusted McNemar test （ Z = -0. 612, P = 0. 540） for TDT. SPSS provided the same result as adjusted McNemar test （ χ^2 = 0. 260, P = 0. 610） did by hand calculation. Conclusion ： Either trios or founders data can be used for the calculation of founder＇s allele frequency when FBAT vl. 7. 3 or PLINK will be employed. When FBAT v2.0. 2e will be employed, founder data has to be prepared. The algorithm of TDT performed by two versions of FBAT or PLANK is McNemar test. The ＂perm＂ option of PLINK TDT command provides exact probability. FBAT and PLINK are genetic analytical tools that can be used for a series of statistical tests with family data. The non - genetic statistical modules of SPSS and SAS are not routines for family data analysis. It is necessary to confirm what type of dataset and algorithm are used by various commands of programs before real analysis in order to avoid misuse and to make reasonable explanation of results.