A Whole-Genome Scan for Stroke or Myocardial Infarction in Family Blood Pressure Program Families

Abstract

Atherothrombotic diseases, including stroke and myocardial infarction, share a common pathogenesis. Chromosomal regions have been linked to atherothrombotic diseases in family studies, and association studies have identified candidate gene polymorphisms that affect the risk of stroke and/or myocardial infarction. Using data from the Family Blood Pressure Program, we tested for chromosomal regions linked to the composite phenotype of stroke or myocardial infarction in a large set of hypertensive families. Nonparametric linkage analysis was implemented in MERLIN, which tests for excess allele-sharing among affected siblings. Empirical distributions based on gene dropping simulations were constructed for each test statistic, and the -log(10) of the associated probability values were compared. Analyses were based on 9607 individuals in 226 black, 395 Hispanic, and 207 white families; 106 families had multiple affected individuals. Several regions showed linkage to stroke or myocardial infarction, most significantly in Hispanics on chromosomes 2p21 (-log(10) P=3.0) and 7q21.1 (-log(10) P=2.8), 9q32 in blacks and Hispanics (-log(10) P=3.0), 11p13 in blacks (-log(10) P=2.1), and 12q24.33 in whites (-log(10) P=3.0). There is statistically significant evidence for loci affecting stroke or myocardial infarction on chromosomes 2, 9, and 12.