Visscher Peter M, Duffy David L
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia.
Genet Epidemiol. 2006 Jan;30(1):30-6. doi: 10.1002/gepi.20124.
The additional statistical power of association studies for quantitative traits was derived when ungenotyped relatives with phenotypes are included in the analysis. It was shown that the extra power is a simple function of the coefficient of additive genetic relationship and the phenotypic correlation coefficient between the genotyped and ungenotyped relatives. For close relatives, such as pairs of fullsibs and identical twin pairs, gains in power in the range of 10 to 30% are achieved if only one of the pair is genotyped. The theoretical results were verified by simulations. It was shown that ignoring the error in estimating the genotype of the ungenotyped relative has little impact on the estimates and on statistical power, consistent with results from quantitative trait loci (QTL) linkage studies. For genome-wide association studies in which not all relatives with phenotypes can be genotyped, our study provides a prediction of the additional power of an analysis that includes phenotypes on ungenotyped individuals, and can be used in experimental design. We show that a two-step procedure, in which missing genotypes are imputed and subsequently an association analysis is performed, is efficient and powerful.
当将具有表型的未分型亲属纳入分析时，数量性状关联研究的额外统计效能得以推导得出。结果表明，额外效能是加性遗传关系系数以及分型亲属与未分型亲属之间表型相关系数的简单函数。对于近亲，如全同胞对和同卵双胞胎对，如果仅对其中一对中的一个进行基因分型，则效能可提高10%至30%。理论结果通过模拟得到了验证。结果表明，忽略未分型亲属基因型估计中的误差对估计值和统计效能影响很小，这与数量性状基因座（QTL）连锁研究的结果一致。对于并非所有具有表型的亲属都能进行基因分型的全基因组关联研究，我们的研究提供了对包含未分型个体表型的分析的额外效能的预测，可用于实验设计。我们表明，两步法，即先推算缺失基因型，随后进行关联分析，是高效且有力的。
