Rare genetic variant analysis on blood pressure in related samples.

The genetic variants associated with blood pressure identified so far explain only a small proportion of the total heritability of this trait. With recent advances in sequencing technology and statistical methodology, it becomes feasible to study the association between blood pressure and rare genetic variants. Using real baseline phenotype data and imputed dosage data from Genetic Analysis Workshop 18, we performed a candidate gene association analysis. We focused on 8 genes shown to be associated with either systolic or diastolic blood pressure to identify the association with both common and rare genetic variants, and then did a genome-wide rare-variant analysis on blood pressure. We performed association analysis for rare coding and splicing variants within each gene region and all rare variants in each sliding window, using either burden tests or sequence kernel association tests accounting for familial correlation. With a sample size of only 747, we failed to find any novel associated genetic loci. Consequently, we performed analyses on simulated data, with knowledge of the underlying simulating model, to evaluate the type I error rate and power for the methods used in real data analysis.