Shih Mei-Chiung, Whittemore Alice S
Department of Health Research and Policy, Stanford University, Stanford, California 94305, USA.
Genet Epidemiol. 2002 Feb;22(2):128-45. doi: 10.1002/gepi.0151.
We use likelihood-based score statistics to test for association between a disease and a diallelic polymorphism, based on data from arbitrary types of nuclear families. The Nonfounder statistic extends the transmission disequilibrium test (TDT) to accommodate affected and unaffected offspring, missing parental genotypes, phenotypes more general than qualitative traits, such as censored survival data and quantitative traits, and residual correlation of phenotypes within families. The Founder statistic compares observed or inferred parental genotypes to those expected in the general population. Here the genotypes of affected parents and those with many affected offspring are weighted more heavily than unaffected parents and those with few affected offspring. We illustrate the tests by applying them to data on a polymorphism of the SRD5A2 gene in nuclear families with multiple cases of prostate cancer. We also use simulations to compare the power of these family-based statistics to that of the score statistic based on Cox's partial likelihood for censored survival data, and find that the family-based statistics have considerably more power when there are many untyped parents. The software program FGAP for computing test statistics is available at http://www.stanford.edu/dept/HRP/epidemiology/FGAP.
我们基于来自任意类型核心家庭的数据，使用基于似然性的评分统计量来检验疾病与双等位基因多态性之间的关联性。非奠基者统计量扩展了传递不平衡检验（TDT），以适应受影响和未受影响的后代、缺失的亲本基因型、比定性性状更一般的表型，如删失生存数据和定量性状，以及家庭内表型的残余相关性。奠基者统计量将观察到的或推断出的亲本基因型与一般人群中预期的基因型进行比较。在这里，受影响的父母以及有许多受影响后代的父母的基因型比未受影响的父母以及有少数受影响后代的父母的基因型权重更大。我们通过将这些检验应用于有多例前列腺癌的核心家庭中SRD5A2基因多态性的数据来说明这些检验。我们还使用模拟来比较这些基于家庭的统计量与基于Cox偏似然性的删失生存数据评分统计量的检验效能，并且发现当有许多未分型的父母时，基于家庭的统计量具有更高的检验效能。用于计算检验统计量的软件程序FGAP可在http://www.stanford.edu/dept/HRP/epidemiology/FGAP获取。
