Evaluating gene by sex and age interactions on cardiovascular risk factors in Brazilian families

Abstract

BackgroundIn family studies, it is important to evaluate the impact of genes and environmental factors on traits of interest. In particular, the relative influences of both genes and the environment may vary in different strata of the population of interest, such as young and old individuals, or males and females.MethodsIn this paper, extensions of the variance components model are used to evaluate heterogeneity in the genetic and environmental variance components due to the effects of sex and age (the cutoff between young and old was 43 yrs). The data analyzed were from 81 Brazilian families (1,675 individuals) of the Baependi Family Heart Study.ResultsThe models allowing for heterogeneity of variance components by sex suggest that genetic and environmental variances are not different in males and females for diastolic blood pressure, LDL-cholesterol, and HDL-cholesterol, independent of the covariates included in the models. However, for systolic blood pressure, fasting glucose and triglycerides, the evidence for heterogeneity was dependent on the covariates in the model. For instance, in the presence of sex and age covariates, heterogeneity in the genetic variance component was suggested for fasting glucose. But, for systolic blood pressure, there was no evidence of heterogeneity in any of the two variance components. Except for the LDL-cholesterol, models allowing for heterogeneity by age provide evidence of heterogeneity in genetic variance for triglycerides and systolic and diastolic blood pressure. There was evidence of heterogeneity in environmental variance in fasting glucose and HDL-cholesterol.ConclusionsOur results suggest that heterogeneity in trait variances should not be ignored in the design and analyses of gene-finding studies involving these traits, as it may generate additional information about gene effects, and allow the investigation of more sophisticated models such as the model including sex-specific oligogenic variance components.

Heritability and Sex-Specific Genetic Effects of Self-Reported Physical Activity in a Brazilian Highly Admixed Population

“…Regarding the fixed effects (covariates) used in the model, we opted for sex, age, age 2 , and interactions between those, which comprise the model most recommended in genetic studies [15,16,23]. In order to account for the ancestry background in our sample, we also included and tested ancestry coefficients that are the two main principal components (pca1 and pca2) estimated for our sample from the Brazilian population as previously described [24].…”

“…The heritability estimates for PA traits were calculated through the variance components approach implemented in SOLAR-Eclipse 8.3.1 package. Assuming the trait follows a normal distribution, the covariance between traits for individuals i and i′ is given by [15]:…”

“…These study designs are especially suitable for the estimation of the proportion of phenotypic variance that is accounted for by additive genetic effects (heritability) and have, for instance, found values as high as 62 and 50% for vertical jump and flexibility, respectively [10,11]. Nonetheless, most of the genetic studies of PA-related phenotypes have been conducted in European and American cohorts [7,[12][13][14] and, to our knowledge, very few have focused on the Brazilian population [15,16]. This population is of particular interest because of its history of migration and high admixture, which accounts for its rich, unique, and diverse genetic background.…”

Cohort profile: the Baependi Heart Study—a family-based, highly admixed cohort study in a rural Brazilian town

“…Subsequent studies identified that age-at-onset is a useful trait for gene mapping of common complex diseases 21 and reported that heterogeneity in trait variances needs to be accounted for in the design and analyses of trait orientated gene finding studies. 22 Lifestyle factors, including physical activity 23 and smoking 24 have also been a focus of the study. The study has been extended to also include aspects of mental health, another major non-communicable disease complex forming a large burden to society.…”

THE BAEPENDI “LITTLE HEART” STUDY: Strategies in Child Education Related to Cardiometabolic Risk Factors for Reducing Morbidity and Mortality in a Developing Country

“…The Baependi Heart Study is the first studies in Brazil clustering families for analyze the relationship between genetic and cardiovascular risk factors [1][2][3][4][5][6]. It had started in 2005 with partnerships among some Brazilian Universities for research and outreach projects.…”