A comparative study of three methods for detecting association of quantitative traits in samples of related subjects
2009
Vitezica, Zulma | Martinez, Maria
We used Genetic Analysis Workshop 16 Problem 3 Framingham Heart Study simulated data set tocompare methods for association analysis of quantitative traits in related individuals. Morespecifically, we investigated type I error and relative power of three approaches: the measuredgenotype, the quantitative transmission-disequilibrium test (QTDT), and the quantitative traitlinkage-disequilibrium (QTLD) tests. We studied high-density lipoprotein and triglyceride (TG)lipid variables, as measured at Visit 1. Knowing the answers, we selected three true major genes forhigh-density lipoprotein and/or TG. Empirical distributions of the three association models werederived from the first 100 replicates. In these data, all three models were similar in error rates.Across the three association models, the power was the lowest for the functional SNP withsmallest size effects (i.e., a2), and for the less heritable trait (i.e., TG). Our results showed thatmeasured genotype outperformed the two orthogonal-based association models (QTLD, QTDT),even after accounting for population stratification. QTDT had the lowest power rates. This isconsistent with the amount of marker and trait data used by each association model. While theeffective sample sizes varied little across our tested variants, we observed some large power dropsand marked differences in performances of the models. We found that the performancescontrasted the most for the tightly linked, but not associated, functional variants.
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