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(Reference retrieved automatically from SciELO through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Effect of race, genetic population structure, and genetic models in two-locus association studies: clustering of functional renin-angiotensin system gene variants in hypertension association studies

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Author(s):
A.C. Pereira [1] ; G.A. Mota [2] ; I. Benseñor [3] ; P.A. Lotufo [4] ; J.E. Krieger
Total Authors: 5
Affiliation:
[1] Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração - Brasil
[2] Universidade de São Paulo. Faculdade de Medicina. Instituto do Coração - Brasil
[3] Universidade de São Paulo. Faculdade de Medicina. Departamento de Clínica Médica - Brasil
[4] Universidade de São Paulo. Faculdade de Medicina. Departamento de Clínica Médica - Brasil
Total Affiliations: 5
Document type: Journal article
Source: Brazilian Journal of Medical and Biological Research; v. 34, n. 11, p. 1421-1428, 2001-11-00.
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. (AU)

FAPESP's process: 01/00009-0 - An integrated approach for the dissection of primary hypertension: molecular and functional characterization of the cardiovascular system
Grantee:Eduardo Moacyr Krieger
Support Opportunities: Research Projects - Thematic Grants