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Recent developments in genetic sequencing technology now make it possible to genotype large numbers of single nucleotide polymorphisms (SNPs) in large samples. Many association studies using SNP data are now being carried out. Typically, these observational studies establish whether certain haplotypes or individual SNPs are associated with a health outcome. Few methods exist for finding interaction effects among multiple SNPs or between SNPs and environmental factors. In this paper, the authors describe logic regression, an exploratory method with which to identify interactions for further research. They illustrate this method using data from a US case-control study of myocardial infarction and stroke (1995–1999) carried out among 1,614 persons in Washington State who were genotyped for 32 SNPs on five genes in the renin-angiotensin system. [ABSTRACT FROM AUTHOR]

The products of the renin-angiotensin system (RAS) play an important role in the pathogenesis of cardiovascular disease. Studies examining RAS gene variants and cardiovascular disease have focused on single-nucleotide polymorphisms (SNPs) rather than haplotypes, which better characterize the patterns of genetic variation. The authors conducted a population-based, case-control study at Group Health (Seattle, Washington) between 1995 and 1999 to determine whether common haplotypes in the angiotensinogen gene (AGT), the renin gene, the angiotensin-converting enzyme gene, and the angiotensin II receptor type 1 and receptor type 2 genes were associated with the risk of myocardial infarction and stroke among pharmacologically treated hypertensive patients. SNP discovery was done using 23 European-origin samples. Thirty tagSNPs (the minimum sets of SNPs that capture most of the haplotype diversity within a block) were genotyped in cases and controls. Haplotypes were inferred using the program PHASE (http://www.stat.washington.edu/stephens/software.html). The authors used weighted logistic regression to estimate associations and conducted a permutation test to estimate the probability of a chance finding. AGT haplotype B was associated with the risk of myocardial infarction (odds ratio = 1.58, 95% confidence interval: 1.06, 2.35); however, results were not statistically significant given the number of tests performed (permutation p = 0.17). In this case-control study, RAS gene haplotypes were not significantly associated with increased risks of myocardial infarction or stroke. [ABSTRACT FROM AUTHOR]