Camila Maciel de Oliveira

Heritability of cardiovascular risk factors in a Brazilian population: Baependi Heart Study

BackgroundThe heritability of cardiovascular risk factors is expected to differ between populations because of the different distribution of environmental risk factors, as well as the genetic make-up of different human populations.MethodsThe purpose of this analysis was to evaluate genetic and environmental influences on cardiovascular risk factor traits, using a variance component approach, by estimating the heritability of these traits in a sample of 1,666 individuals in 81 families ascertained randomly from a highly admixed population of a city in a rural area in Brazil.ResultsBefore adjustment for sex, age, age2, and age × sex interaction, polygenic heritability of systolic (SBP) and diastolic (DBP) blood pressure were 15.0% and 16.4%, waist circumference 26.1%, triglycerides 25.7%, fasting glucose 32.8%, HDL-c 31.2%, total cholesterol 28.6%, LDL-c 26.3%, BMI 39.1%. Adjustment for covariates increased polygenic heritability estimates for all traits mainly systolic and diastolic blood pressure (25.9 and 26.2%, respectively), waist circumference (40.1%), and BMI (51.0%).ConclusionHeritability estimates for cardiovascular traits in the Brazilian population are high and not significantly different from other studied worldwide populations. Mapping efforts to identify genetic loci associated with variability of these traits are warranted.

Body mass index, waist circumference, body adiposity index, and risk for type 2 diabetes in two populations in Brazil: general and Amerindian.

Objective The use of the anthropometric indices of adiposity, especially body mass index and waist circumference in the prediction of diabetes mellitus has been widely explored. Recently, a new body composition index, the body adiposity index was proposed. The aim of this study was to compare the effectiveness of body mass index, waist circumference, and body adiposity index in the risk assessment for type 2 diabetes mellitus. Design and methods A total of 1,572 individuals from the general population of Vitoria City, Brazil and 620 Amerindians from the Aracruz Indian Reserve, Brazil were randomly selected. BMI, waist circumference, and BAI were determined according to a standard protocol. Type 2 diabetes mellitus was diagnosed by the presence of fasting glucose ≥126 mg/dL or by the use of antidiabetic drugs. Results The area under the curve was similar for all anthropometric indices tested in the Amerindian population, but with very different sensitivities or specificities. In women from the general population, the area under the curve of waist circumference was significantly higher than that of the body adiposity index. Regarding risk assessment for type 2 diabetes mellitus, the body adiposity index was a better risk predictor than body mass index and waist circumference in the Amerindian population and was the index with highest odds ratio for type 2 diabetes mellitus in men from the general population, while in women from the general population waist circumference was the best risk predictor. Conclusion Body adiposity index was the best risk predictor for type 2 diabetes mellitus in the Amerindian population and men from the general population. Our data suggest that the body adiposity index is a useful tool for the risk assessment of type 2 diabetes mellitus in admixture populations.

Heritability of physical activity traits in Brazilian families: the Baependi Heart Study

BackgroundIt is commonly recognized that physical activity has familial aggregation; however, the genetic influences on physical activity phenotypes are not well characterized. This study aimed to (1) estimate the heritability of physical activity traits in Brazilian families; and (2) investigate whether genetic and environmental variance components contribute differently to the expression of these phenotypes in males and females.MethodsThe sample that constitutes the Baependi Heart Study is comprised of 1,693 individuals in 95 Brazilian families. The phenotypes were self-reported in a questionnaire based on the WHO-MONICA instrument. Variance component approaches, implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package, were applied to estimate the heritability and to evaluate the heterogeneity of variance components by gender on the studied phenotypes.ResultsThe heritability estimates were intermediate (35%) for weekly physical activity among non-sedentary subjects (weekly PA_NS), and low (9-14%) for sedentarism, weekly physical activity (weekly PA), and level of daily physical activity (daily PA). Significant evidence for heterogeneity in variance components by gender was observed for the sedentarism and weekly PA phenotypes. No significant gender differences in genetic or environmental variance components were observed for the weekly PA_NS trait. The daily PA phenotype was predominantly influenced by environmental factors, with larger effects in males than in females.ConclusionsHeritability estimates for physical activity phenotypes in this sample of the Brazilian population were significant in both males and females, and varied from low to intermediate magnitude. Significant evidence for heterogeneity in variance components by gender was observed. These data add to the knowledge of the physical activity traits in the Brazilian study population, and are concordant with the notion of significant biological determination in active behavior.

Genetic analyses of smoking initiation, persistence, quantity, and age-at-onset of regular cigarette use in Brazilian families: the Baependi Heart Study

BackgroundThe purpose of this study was to estimate the genetic influences on the initiation of cigarette smoking, the persistence, quantity and age-at-onset of regular cigarette use in Brazilian families.MethodsThe data set consisted of 1,694 individuals enrolled in the Baependi Heart Study. The heritability and the heterogeneity in genetic and environmental variance components by gender were estimated from variance components approaches, using the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package. The mixed-effects Cox model was used for the genetic analysis of the age-at onset of regular cigarette use.ResultsThe heritability estimates were high (> 50%) for smoking initiation and were intermediate, ranging from 23.4 to 31.9%, for smoking persistence and quantity. Significant evidence for heterogeneity in variance components by gender was observed for smoking initiation and age-at-onset of regular cigarette use. Genetic factors play an important role in the interindividual variation of these phenotypes in females, while in males there is a predominant environmental component, which could be explained by greater social influences in the initiation of tobacco use.ConclusionsSignificant heritabilities were observed in smoking phenotypes for both males and females from the Brazilian population. These data add to the literature and are concordant with the notion of significant biological determination in smoking behavior. Samples from the Baependi Heart Study may be valuable for the mapping of genetic loci that modulate this complex biological trait.

Shared Genetic Factors of Anxiety and Depression Symptoms in a Brazilian Family-Based Cohort, the Baependi Heart Study.

To investigate the phenotypic and genetic overlap between anxiety and depression symptoms in an admixed population from extended family pedigrees. Participants (n = 1,375) were recruited from a cohort of 93 families (mean age±SD 42±16.3, 57% female) in the rural town of Baependi, Brazil. The Hospital Anxiety and Depression Scale (HADS) was used to assess depression and anxiety symptoms. Heritability estimates were obtained by an adjusted variance component model. Bivariate analyses were performed to obtain the partition of the covariance of anxiety and depression into genetic and environmental components, and to calculate the genetic contribution modulating both sets of symptoms. Anxiety and depression scores were 7.49±4.01 and 5.70±3.82, respectively. Mean scores were affected by age and were significantly higher in women. Heritability for depression and anxiety, corrected for age and sex, were 0.30 and 0.32, respectively. Significant genetic correlations (ρg = 0.81) were found between anxiety and depression scores; thus, nearly 66% of the total genetic variance in one set of symptoms was shared with the other set. Our results provided strong evidence for a genetic overlap between anxiety and depression symptoms, which has relevance for our understanding of the biological basis of these constructs and could be exploited in genome-wide association studies.

Endurance training inhibits insulin clearance and IDE expression in Swiss mice.

Introduction Endurance training improves peripheral insulin sensitivity in the liver and the skeletal muscle, but the mechanism for this effect is poorly understood. Recently, it was proposed that insulin clearance plays a major role in both glucose homeostasis and insulin sensitivity. Therefore, our goal was to determine the mechanism by which endurance training improves insulin sensitivity and how it regulates insulin clearance in mice. Methods Mice were treadmill-trained for 4 weeks at 70–80% of maximal oxygen consumption (VO2 max) for 60 min, 5 days a week. The glucose tolerance and the insulin resistance were determined using an IPGTT and an IPITT, respectively, and the insulin decay rate was calculated from the insulin clearance. Protein expression and phosphorylation in the liver and the skeletal muscle were ascertained by Western blot. Results Trained mice exhibited an increased VO2 max, time to exhaustion, glucose tolerance and insulin sensitivity. They had smaller fat pads and lower plasma concentrations of insulin and glucose. Endurance training inhibited insulin clearance and reduced expression of IDE in the liver, while also inhibiting insulin secretion by pancreatic islets. There was increased phosphorylation of both the canonical (IR-AKT) and the non-canonical (CaMKII-AMPK-ACC) insulin pathways in the liver of trained mice, whereas only the CaMKII-AMPK pathway was increased in the skeletal muscle. Conclusion Endurance training improved glucose homeostasis not only by increasing peripheral insulin sensitivity but also by decreasing insulin clearance and reducing IDE expression in the liver.

Genetic analysis of age-at-onset for cardiovascular risk factors in a Brazilian family study.

Background/Aims: Statistical analysis of age-at-onset involving family data is particularly complicated because there is a correlation pattern that needs to be modeled and also because there are measurements that are censored. In this paper, our main purpose was to evaluate the effect of genetic and shared family environmental factors on age-at-onset of three cardiovascular risk factors: hypertension, diabetes and high cholesterol. Methods: The mixed-effects Cox model proposed by Pankratz et al. [2005] was used to analyze the data from 81 families, involving 1,675 individuals from the village of Baependi, in the state of Minas Gerais, Brazil. Results: The analyses performed showed that the polygenic effect plays a greater role than the shared family environmental effect in explaining the variability of the age-at-onset of hypertension, diabetes and high cholesterol. The model which simultaneously evaluated both effects indicated that there are individuals which may have risk of hypertension due to polygenic effects 130% higher than the overall average risk for the entire sample. For diabetes and high cholesterol the risks of some individuals were 115 and 45%, respectively, higher than the overall average risk for the entire population. Conclusions: Results showed evidence of significant polygenic effects indicating that age-at-onset is a useful trait for gene mapping of the common complex diseases analyzed. In addition, we found that the polygenic random component might absorb the effects of some covariates usually considered in the risk evaluation, such as gender, age and BMI.

Heritability of arterial stiffness in a Brazilian population: Baependi Heart Study.

Background: Increased arterial stiffness is an important determinant of cardiovascular disease risk. In addition, it has been recognized that arterial stiffness has familial aggregation; however, there are no studies involving Brazilian families. Thus, the aim of this study was to evaluate the heritability of arterial stiffness in a Brazilian population. Methods: In this study, 1675 eligible individuals (both sexes and aged 18–102 years) were distributed in 125 families resident in the municipality of Baependi, a city located in the southeast of Brazil. Carotid–femoral pulse wave velocity (PWV) was measured with a noninvasive automatic device (Complior; Artech Medical, Pantin, France). Variance component approaches, implemented in the SOLAR computer package (San Antonio, Texas, USA), were applied to estimate the heritability of the studied phenotype under different statistical models. Results: Heritability estimates for carotid–femoral PWV stratified by age ranging from 11 to 35% (higher in individuals aged ⩽45 years and lower in individuals aged 18–102 years). Age and hypertension showed significant effects on the PWV trait and significantly affect heritability estimates in all models. Conclusion: We conclude that the heritability of carotid–femoral PWV in a Brazilian population is intermediate, and therefore genetic studies evolving arterial stiffness phenotypes should be encouraged.

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

Purpose Cardiovascular disease (CVD) is a major challenge to global health. The same epidemiological transition scenario is replayed as countries develop, but with variations based on environment, culture and ethnic mixture. The Baependi Heart Study was set up in 2005 to develop a longitudinal family-based cohort study that reflects on some of the genetic and lifestyle-related peculiarities of the Brazilian populations, in order to evaluate genetic and environmental influences on CVD risk factor traits. Participants Probands were recruited in Baependi, a small rural town in the state of Minas Gerais, Brazil, following by first-degree and then increasingly more distant relatives. The first follow-up wave took place in 2010, and the second in 2016. At baseline, the study evaluated 1691 individuals across 95 families. Cross-sectional data have been collected for 2239 participants. Findings to date Environmental and lifestyle factors and measures relevant to cardiovascular health have been reported. Having expanded beyond cardiovascular health outcomes, the phenotype datasets now include genetics, biochemistry, anthropometry, mental health, sleep and circadian rhythms. Many of these have yielded heritability estimates, and a shared genetic background of anxiety and depression has recently been published. In spite of universal access to electricity, the population has been found to be strongly shifted towards morningness compared with metropolitan areas. Future plans A new follow-up, marking 10 years of the study, is ongoing in 2016, in which data are collected as in 2010 (with the exception of the neuropsychiatric protocol). In addition to this, a novel questionnaire package collecting information about intelligence, personality and spirituality is being planned. The data set on circadian rhythms and sleep will be amended through additional questionnaires, actimetry, home sleep EEG recording and dim light melatonin onset (DLMO) analysis. Finally, the anthropometric measures will be expanded by adding three-dimensional facial photography, voice recording and anatomical brain MRI.

Association between anthropometric indicators of adiposity and hypertension in a Brazilian population: Baependi Heart Study.

Background Recently, some studies have evaluated the role of adiposity measures in the prediction of hypertension risk, but the results are conflicting. Thus, the aim of this study was to compare which of the four indicators of adiposity (waist circumference–WC, body mass index–BMI, body adiposity index–BAI, and visceral adiposity index–VAI) were better associated with hypertension in a Brazilian population. Methods and findings For this study, were selected 1627 individuals (both genders, and aged over 18 years) resident in the municipality of Baependi, a city located in the Southeast of Brazil. WC, BMI, BAI and VAI were determined according to a standard protocol. Hypertension was defined as mean systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, and/or antihypertensive drug use. The indicators of adiposity WC, BMI, BAI, and VAI were higher in hypertensive when compared to non-hypertensive individuals. In addition, WC and BMI were most strongly associated with hypertension in men and women, respectively. The area under the curve (AUC) of WC was significantly higher than VAI in men. In women, both AUC of BMI and WC showed higher discriminatory power to predict hypertension than BAI and VAI. Conclusions The indicators of adiposity WC and BMI were better associated with hypertension than BAI and VAI, in both genders, and it could be a useful tools for the screening of hypertensive patients.