COMPARISON OF A UNIFIED APPROACH AND THE TDT IN THE FRAMINGHAM HEART STUDY

Case Western Reserve University, Cleveland OH

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Population stratification is one of the major causes of spurious associations in association studies. A unified association approach (FamCC) based on principal component analysis can overcome the effect of population stratification, as well as make use of both family and unrelated samples combined to increase power. In this study, we compared FamCC and the transmission disequilibrium test (TDT) using data on hypertension, systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the Framingham heart study. Our study indicated FamCC has reasonable type I error for both unrelated samples and family samples for all three traits. For the binary trait hypertension, we found results from FamCC were inconsistent with those from the TDT. We discuss the reasons for this inconsistency. After correcting for multiple tests, we did not detect any significant SNPs by either FamCC or the TDT. The results from FamCC and the TDT were most consistent for the quantitative trait DBP and least consistent for the binary trait hypertension.