Comparison of a unified analysis approach for family and unrelated samples with the transmission-disequilibrium test to study associations of hypertension in the Framingham Heart Study

Population stratification is one of the major causes of spurious associations in association studies. A unified association approach 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 (family-case-control, or FamCC). In this study, we compared FamCC and the transmission-disequilibrium test (TDT) using data on hypertension, systolic blood pressure, and diastolic blood pressure in the Framingham Heart Study. Our study indicated FamCC has reasonable type I error for both the unrelated sample and the family sample for all three traits. For these three traits, 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 single-nucleotide polymorphisms by either FamCC or the TDT.