Abstract
Previous genetic association studies have overlooked the potential for biased results when analyzing different population structures in ethnically diverse populations. The purpose of the present study was to quantify this bias in two-locus association studies conducted on an admixtured urban population. We studied the genetic structure distribution of angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen methionine/threonine (M/T) polymorphisms in 382 subjects from three subgroups in a highly admixtured urban population. Group I included 150 white subjects; group II, 142 mulatto subjects, and group III, 90 black subjects. We conducted sample size simulation studies using these data in different genetic models of gene action and interaction and used genetic distance calculation algorithms to help determine the population structure for the studied loci. Our results showed a statistically different population structure distribution of both ACE I/D (P = 0.02, OR = 1.56, 95% CI = 1.05-2.33 for the D allele, white versus black subgroup) and angiotensinogen M/T polymorphism (P = 0.007, OR = 1.71, 95% CI = 1.14-2.58 for the T allele, white versus black subgroup). Different sample sizes are predicted to be determinant of the power to detect a given genotypic association with a particular phenotype when conducting two-locus association studies in admixtured populations. In addition, the postulated genetic model is also a major determinant of the power to detect any association in a given sample size. The present simulation study helped to demonstrate the complex interrelation among ethnicity, power of the association, and the postulated genetic model of action of a particular allele in the context of clustering studies. This information is essential for the correct planning and interpretation of future association studies conducted on this population.
Highlights
Previous genetic association studies have overlooked the potential for biased results when analyzing different population structures in ethnically diverse populations
We studied the genetic structure distribution of angiotensin-converting enzyme insertion/deletion (ACE I/ D) and angiotensinogen methionine/threonine (M/T) polymorphisms in 382 subjects from three subgroups in a highly admixtured urban population
We conducted sample size simulation studies using these data in different genetic models of gene action and interaction and used genetic distance calculation algorithms to help determine the population structure for the studied loci
Summary
Previous genetic association studies have overlooked the potential for biased results when analyzing different population structures in ethnically diverse populations. Studies with putative genetic risk factors for hypertension have been criticized by many investigators because their results have not been consistent [1]. Variants of the renin-angiotensin system (RAS) genes have the potential to reveal certain aspects of the genesis of some cardiovascular diseases. Two of these allelic variants have been undoubtedly associated with particular intermediate phenotypes that could help explain the RAS role in some of the pathophysiological derangements observed in cardiovascular homeostasis in a number of diseases [2,3]. Its role in predicting hypertension and other cardiovascular diseases (e.g., myocardial infarction, cardiac hypertrophy) [4,5,6,7,8,9,10] remains
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