Martin R B, Alda M, MacLean C J
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond 23298, USA.
Genet Epidemiol. 1998;15(5):471-90. doi: 10.1002/(SICI)1098-2272(1998)15:5<471::AID-GEPI3>3.0.CO;2-3.
Intended to resolve the problem of constructing a matched population-based control sample, haplotype relative risk techniques frequently suffer from loss of power for late-onset diseases due to unavailability of parental genotypes that are required to form parent-offspring pairs. However, much of this missing information can be reconstructed using the genotypes of the affected individual's siblings. For some cases, an estimate of the marker-allele frequencies for controls is needed. We have developed a technique based upon this idea and call it PGR (Parental Genotype Reconstruction). PGR represents a combination of the internal controls used by haplotype relative risk and controls based upon estimated allele frequencies. Although the latter is just what haplotype relative risk was designed to avoid, PGR has the potential to substantially boost power to detect linkage disequilibrium, for a relatively small increase in type I error. This performance is reasonably robust with respect to errors in the estimated allele frequencies, as we demonstrate by numerical simulation. A PGR software package has been written in FORTRAN and is available from Dr. Martin's web site at http://electro.psi.vcu.edu/rmartin/.
为了解决构建基于匹配人群的对照样本的问题，单倍型相对风险技术经常因构建亲代-子代对所需的亲代基因型不可用而在晚发性疾病中出现效能损失。然而，许多缺失的信息可以利用受影响个体兄弟姐妹的基因型来重建。对于某些情况，需要估计对照的标记等位基因频率。我们基于这一想法开发了一种技术，并将其称为PGR（亲代基因型重建）。PGR代表了单倍型相对风险中使用的内部对照与基于估计等位基因频率的对照的结合。虽然后者正是单倍型相对风险旨在避免的情况，但PGR有潜力在第一类错误相对小幅增加的情况下大幅提高检测连锁不平衡的效能。正如我们通过数值模拟所证明的，这种性能对于估计等位基因频率中的误差相当稳健。一个PGR软件包已用FORTRAN编写，可从马丁博士的网站http://electro.psi.vcu.edu/rmartin/获取。
