Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.

Metabolic syndrome alters relationships between cardiometabolic variables, cognition and white matter hyperintensity load.

Cardiometabolic risk factors influence white matter hyperintensity (WMH) development: in metabolic syndrome (MetS), higher WMH load is often reported but the relationships between specific cardiometabolic variables, WMH load and cognitive performance are uncertain. We investigated these in a Brazilian sample (aged 50-85) with (N = 61) and without (N = 103) MetS. Stepwise regression models identified effects of cardiometabolic and demographic variables on WMH load (from FLAIR MRI) and verbal recall performance. WMH volume was greater in MetS, but verbal recall performance was not impaired. Age showed the strongest relationship with WMH load. Across all participants, systolic blood pressure (SBP) and fasting blood glucose were also contributors, and WMH volume was negatively associated with verbal recall performance. In non-MetS, higher HbA1c, SBP, and number of MetS components were linked to poorer recall performance while higher triglyceride levels appeared to be protective. In MetS only, these relationships were absent but education exerted a strongly protective effect on recall performance. Thus, results support MetS as a construct: the clustering of cardiometabolic variables in MetS alters their individual relationships with cognition; instead, MetS is characterised by a greater reliance on cognitive reserve mechanisms. In non-MetS, strategies to control HbA1c and SBP should be prioritised as these have the largest impact on cognition.

Heritability of semantic verbal fluency task using time-interval analysis.

Individual variability in word generation is a product of genetic and environmental influences. The genetic effects on semantic verbal fluency were estimated in 1,735 participants from the Brazilian Baependi Heart Study. The numbers of exemplars produced in 60 s were broken down into time quartiles because of the involvement of different cognitive processes-predominantly automatic at the beginning, controlled/executive at the end. Heritability in the unadjusted model for the 60-s measure was 0.32. The best-fit model contained age, sex, years of schooling, and time of day as covariates, giving a heritability of 0.21. Schooling had the highest moderating effect. The highest heritability (0.17) was observed in the first quartile, decreasing to 0.09, 0.12, and 0.0003 in the following ones. Heritability for average production starting point (intercept) was 0.18, indicating genetic influences for automatic cognitive processes. Production decay (slope), indicative of controlled processes, was not significant. The genetic influence on different quartiles of the semantic verbal fluency test could potentially be exploited in clinical practice and genome-wide association studies.

Phenotypic and genetic correlations for body structure scores (frame) with productive traits and index for CEIP classification in Nellore beef cattle.

The present study was carried out to estimate both (co)variance components and genetic parameters for frame scores obtained using two methods (FRAME_GMA and FRAME_BIF) as well as phenotypic and genetic correlations with traits such as weaning weight, weight gain from weaning to yearling, scrotal circumference, muscle score, and an empiric index for animal classification for the Special Certificate of Identification and Production (CEIP). Data on 12,728 animals, raised in Southeastern Brazil, with ages from 490 to 610 days were analyzed. Estimates of heritability for FRAME_GMA and FRAME_BIF in multi-trait analysis were 0.28 and 0.24, respectively. Genetic correlation coefficients between frame scores and the growth trait were of medium magnitude, which indicates that genetic selection for weight resulted in undesirable responses, increasing the animals' frames. Small changes should be expected in the frame of animals that have been submitted to a genetic selection regarding muscle score and scrotal circumference. The low magnitude of phenotypic and genetic correlation between frame scores and the empirical selection index that classifies animals for CEIP, a Brazilian official certificate that recognizes the value of seedstock that is not registered at breeders associations, but is genetically evaluated, does not indicate important responses in giving a CEIP to animals that have been directly or indirectly selected for frame. Other studies must be performed to determine estimates of the genetic parameters for frame scores in other beef cattle populations.

Estimation of genetic parameters for a new model for defining body structure scores (frame scores) in Nellore cattle.

Models for estimation of frame scores in Nellore beef cattle (FRAME_GMA) were developed, comparing them with frame scores estimated using equations proposed by the Beef Improvement Federation (FRAME_BIF, USA). Correlation among frame scores obtained by these two methodologies, along with the independent variables considered in the estimation models, were also studied. A data set with 12,728 animals, with ages between 490 and 610 days, was used. The models that best adjusted to FRAME_GMA included hip height, weight and interaction between height and weight. Estimates of heritability for FRAME_GMA and FRAME_BIF were 0.26 +/- 0.03 and 0.23 +/- 0.03, respectively, in single trait analysis, and 0.28 and 0.24, respectively, in multi-trait analysis. Phenotypic Pearson and Spearman correlation coefficients between FRAME_GMA and FRAME_BIF for males were 0.87 and 0.83, respectively, being lower than those found for females (0.92 for both coefficients). Genetic correlation between the frame scores did not differ between genders, with values of 0.92 for the Pearson coefficient and 0.91 for the Spearman coefficient. We concluded that FRAME_GMA was better adapted to this data set than FRAME_BIF. Other studies need to be made to evaluate the applicability of this proposed model to other populations of Nellore beef cattle and for other age groups.

Timing and quality of sleep in a rural Brazilian family-based cohort, the Baependi Heart Study.

Sleep is modulated by several factors, including sex, age, and chronotype. It has been hypothesised that contemporary urban populations are under pressure towards shorter sleep duration and poorer sleep quality. Baependi is a small town in Brazil that provides a window of opportunity to study the influence of sleep patterns in a highly admixed rural population with a conservative lifestyle. We evaluated sleep characteristics, excessive daytime sleepiness, and chronotype using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Morningness-Eveningness Questionnaire questionnaires, respectively. The sample consisted of 1,334 subjects from the Baependi Heart study (41.5% male; age: 46.5 ± 16.2 y, range: 18-89 years). Average self-reported sleep duration was 07:07 ± 01:31 (bedtime 22:32 ± 01:27, wake up time: 06:17 ± 01:25 hh:min), sleep quality score was 4.9 + 3.2, chronotype was 63.6 ± 10.8 and daytime sleepiness was 7.4 ± 4.8. Despite a shift towards morningness in the population, chronotype remained associated with reported actual sleep timing. Age and sex modulated the ontogeny of sleep and chronotype, increasing age was associated with earlier sleep time and shorter sleep duration. Women slept longer and later, and reported poorer sleep quality than men (p < 0.0001). This study provides indirect evidence in support of the hypothesis that sleep timing was earlier prior to full urbanisation.

Phenotypic and genetic correlations for body structure scores (frame) with productive traits and index for CEIP classification in Nellore beef cattle

The present study was carried out to estimate both (co)variance components and genetic parameters for frame scores obtained using two methods (FRAME_GMA and FRAME_BIF) as well as phenotypic and genetic correlations with traits such as weaning weight, weight gain from weaning to yearling, scrotal circumference, muscle score, and an empiric index for animal classification for the Special Certificate of Identification and Production (CEIP). Data on 12,728 animals, raised in Southeastern Brazil, with ages from 490 to 610 days were analyzed. Estimates of heritability for FRAME_GMA and FRAME_BIF in multi-trait analysis were 0.28 and 0.24, respectively. Genetic correlation coefficients between frame scores and the growth trait were of medium magnitude, which indicates that genetic selection for weight resulted in undesirable responses, increasing the animals’ frames. Small changes should be expected in the frame of animals that have been submitted to a genetic selection regarding muscle score and scrotal circumference. The low magnitude of phenotypic and genetic correlation between frame scores and the empirical selection index that classifies animals for CEIP, a Brazilian official certificate that recognizes the value of seedstock that is not registered at breeders associations, but is genetically evaluated, does not indicate important responses in giving a CEIP to animals that have been directly or indirectly selected for frame. Other studies must be performed to determine estimates of the genetic parameters for frame scores in other beef cattle populations