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BACKGROUND: Instrumental variables (IVs) can be used to provide evidence as to whether a treatment has a causal effect on an outcome . Even if the instrument satisfies the three core IV assumptions of relevance, independence, and exclusion restriction, further assumptions are required to identify the average causal effect (ACE) of on . Sufficient assumptions for this include homogeneity in the causal effect of on ; homogeneity in the association of with ; and no effect modification. METHODS: We describe the no simultaneous heterogeneity assumption, which requires the heterogeneity in the - causal effect to be mean independent of (i.e., uncorrelated with) both and heterogeneity in the - association. This happens, for example, if there are no common modifiers of the - effect and the - association, and the - effect is additive linear. We illustrate the assumption of no simultaneous heterogeneity using simulations and by re-examining selected published studies. RESULTS: Under no simultaneous heterogeneity, the Wald estimand equals the ACE even if both homogeneity assumptions and no effect modification (which we demonstrate to be special cases of-and therefore stronger than-no simultaneous heterogeneity) are violated. CONCLUSIONS: The assumption of no simultaneous heterogeneity is sufficient for identifying the ACE using IVs. Since this assumption is weaker than existing assumptions for ACE identification, doing so may be more plausible than previously anticipated.
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Causalidade , HumanosRESUMO
BACKGROUND: Interpreting instrumental variable results often requires further assumptions in addition to the core assumptions of relevance, independence, and the exclusion restriction. METHODS: We assess whether instrument-exposure additive homogeneity renders the Wald estimand equal to the average derivative effect (ADE) in the case of a binary instrument and a continuous exposure. RESULTS: Instrument-exposure additive homogeneity is insufficient for ADE identification when the instrument is binary, the exposure is continuous, and the effect of the exposure on the outcome is nonlinear on the additive scale. For a binary exposure, the exposure-outcome effect is necessarily additive linear, so the homogeneity condition is sufficient. CONCLUSIONS: For binary instruments, instrument-exposure additive homogeneity identifies the ADE if the exposure is also binary. Otherwise, additional assumptions (such as additive linearity of the exposure-outcome effect) are required.
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Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined â¼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10-8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10-8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).
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Pressão Sanguínea/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Grupos Raciais/genética , Fumar/genética , Estudos de Coortes , Diástole/genética , Epistasia Genética , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Reprodutibilidade dos Testes , Sístole/genéticaRESUMO
OBJECTIVE: We aimed at evaluating the association of maternal pre-pregnancy nutritional status with offspring anthropometry and body composition. We also evaluated whether these associations were modified by gender, diet and physical activity and mediated by birth weight. DESIGN: Birth cohort study. SETTING: Waist circumference was measured with an inextensible tape, and fat and lean mass were measured using dual-energy X-ray absorptiometry. Multiple linear regression was used to adjust for possible confounders and allele score of BMI. We carried out mediation analysis using G-formula. PARTICIPANTS: In 1982, 1993 and 2004, all maternity hospitals in Pelotas (South Brazil) were visited daily and all live births whose families lived in the urban area of the city were evaluated. These subjects have been followed up at different ages. RESULTS: Offspring of obese mothers had on average higher BMI, waist circumference and fat mass index than those of normal weight mothers, and these differences were higher among daughters. The magnitudes of the association were similar in the cohorts, except for height, where the association pattern was not clear. In the 1982 cohort, further adjustment for a BMI allele score had no material influence on the magnitude of the associations. Mediation analyses showed that birth weight captured part of this association. CONCLUSIONS: Our findings suggest that maternal pre-pregnancy nutritional status is positively associated with offspring BMI and adiposity in offspring. And this association is higher among daughters whose mother was overweight or obese and, birth weight explains part of this association.
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Composição Corporal , Estado Nutricional , Peso ao Nascer , Índice de Massa Corporal , Brasil , Estudos de Coortes , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Studies on mental disorders prevalence and comorbidity, including suicidality, are scarce in low and middle-income settings. We aimed to describe the pattern of comorbidity between mental disorders and their association with suicidality. METHODS: In 1982, all hospital deliveries in Pelotas (Southern Brazil) were identified (nâ¯=â¯5914) and have been prospectively followed. Participants were evaluated for the presence of common mental disorders (CMD) at the ages of 18-19, 23 and 30â¯years. In 2012-13 (30â¯years of age), trained psychologists evaluated 3657 individuals for disorders using the Mini International Neuropsychiatric Interview. RESULTS: Prevalence of suicidal wishing, suicidal planning and lifetime suicidal attempt was 4.9%, 3.8% and 6.6%, respectively. Suicidal wishing was most strongly associated with having joint major depressive episode (MD) and lifetime suicidal attempt (ORâ¯=â¯26.4, 95%CI:13.9-50.4) with comorbid MD with mania/hypomania (ORâ¯=â¯21.2, 95%CI:6.93-65.1). Suicidal planning was most strongly associated with having joint MD and lifetime suicidal attempt (ORâ¯=â¯44.7, 95%CI:22.6-88.4), with comorbid MD and social anxiety disorder (ORâ¯=â¯30.6, 95%CI:13.0-72.0), and joint social anxiety disorder with lifetime suicidal attempt (ORâ¯=â¯26.3, 95%CI:8.33-82.7). Independently of other disorders, prospective and cross-sectional measures of CMD were associated with higher rates of suicidality. LIMITATIONS: We do not have data on suicide deaths in follow-up and the diagnostic instrument used at 30â¯years of age was not used in all previous follow-up. CONCLUSION: MD and social anxiety have independent and combined associations with suicidality, and also with they occur with lifetime suicidal attempt and other mental disorders.
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Transtorno Depressivo Maior , Transtornos Mentais , Suicídio , Adulto , Brasil/epidemiologia , Comorbidade , Estudos Transversais , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Estudos Prospectivos , Fatores de Risco , Ideação Suicida , Adulto JovemRESUMO
Mendelian randomization (MR) has been increasingly used to strengthen causal inference in observational epidemiology. Methodological developments in the field allow detecting and/or adjusting for different potential sources of bias, mainly bias due to horizontal pleiotropy (or "off-target" genetic effects). Another potential source of bias is nonrandom matching between spouses (i.e., assortative mating). In this study, we performed simulations to investigate the bias caused in MR by assortative mating. We found that bias can arise due to either cross-trait assortative mating (i.e., assortment on two phenotypes, such as highly educated women selecting taller men) or single-trait assortative mating (i.e., assortment on a single phenotype), even if the exposure and outcome phenotypes are not the phenotypes under assortment. The simulations also indicate that bias due to assortative mating accumulates over generations and that MR methods robust to horizontal pleiotropy are also affected by this bias. Finally, we show that genetic data from mother-father-offspring trios can be used to detect and correct for this bias.
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Viés , Análise da Randomização Mendeliana , Reprodução/genética , Estatura/genética , Criança , Simulação por Computador , Pai , Feminino , Genótipo , Humanos , Análise dos Mínimos Quadrados , Masculino , Modelos Genéticos , Mães , Fenótipo , Análise de RegressãoRESUMO
BACKGROUND/OBJECTIVES: Attention-deficit hyperactivity disorder (ADHD), one of the most common neurodevelopmental disorders in childhood and adolescence, is associated with obesity in observational studies. However, it is unclear whether ADHD contributes to, results from or is merely correlated with obesity. This study evaluates the presence and direction of a causal effect between ADHD and obesity. SUBJECTS/METHODS: We performed a bidirectional two-sample Mendelian randomization using summary data from consortia of genome-wide association studies to investigate if ADHD (N = 55,374) has a causal effect on body mass index (BMI) in childhood (N = 35,668) and adulthood (N = 322,154-500,000), and vice-versa. The main analysis was performed using the inverse variance weighted (IVW) method. As sensitivity analyses, we used other Mendelian randomization methods that are more robust to horizontal pleiotropy (i.e., MR-Egger, weighted mode, and penalized weighted median estimators), as well as stratified the analysis by the putative mechanisms of genetic instruments (i.e., pathways involved or not in neurological processes). RESULTS: The IVW method indicated a positive causal effect of BMI on ADHD: ß = 0.324 (95% CI 0.198 to 0.449, p < 0.001; expressed as change in ln(odds ratio) of ADHD per each additional SD unit of BMI). IVW estimates were directionally consistent with other methods. On the other hand, we did not find consistent evidence for a causal effect of ADHD genetic liability on BMI. CONCLUSIONS: The results suggested that higher BMI increases the risk of developing ADHD, but not the other way around.
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Transtorno do Deficit de Atenção com Hiperatividade , Índice de Massa Corporal , Obesidade , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Pré-Escolar , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Obesidade/complicações , Obesidade/epidemiologia , População BrancaRESUMO
BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , Inibidores de PCSK9 , Polimorfismo de Nucleotídeo Único , Pró-Proteína Convertase 9/genética , Inibidores de Serina Proteinase/uso terapêutico , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/prevenção & controle , Regulação para Baixo , Dislipidemias/sangue , Dislipidemias/epidemiologia , Estudo de Associação Genômica Ampla , Humanos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Inibidores de Serina Proteinase/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND: Evidence suggests that there is an association between ethnicity/skin color and depression; however, many contextual and individual variables, like sense of discrimination and socioeconomic position (SEP), might influence the direction of this association. We assessed the association between African ancestry and major depression among young adults that have been followed-up since birth in a Southern Brazilian city, and the mediating effect of SEP and discrimination. METHODS: In 1982, all hospital deliveries in Pelotas (Southern Brazil) were identified; liveborns were examined and their mothers interviewed (n = 5914). In 2012-13, at 30 years of age, we used the Mini International Neuropsychiatric Interview (MINI) for major depression diagnosis. In addition, DNA samples were genotyped for approximately 2.5 million single nucleotide polymorphisms (SNPs) using Illumina (CA, USA) HumanOmni2.5-8v1 array. Genomic ancestry estimation was based on approximately 370 000 single nucleotide polymorphisms (SNPs) mutually available for the Pelotas cohort and selected samples (used as reference panels) of the HapMap and Human Genome Diversity (HGDP). We estimated prevalence ratios (PR) using Poisson regression models and evaluated the association between percentage of African ancestry and major depression. We used G-computation for mediation analysis. RESULTS: At 30 years, 3576 individuals were evaluated for major depression (prevalence = 7.9 %). Only individuals in the highest SEP, who had a percentage of African ancestry between >5-30 % and >30 % had a prevalence of major depression 2.16 (PR = 2.16 95 % CI [1.05-4.45]) and 2.74 (PR = 2.74 95 % CI [1.06-7.06]) times higher, than those with 5 % or less, respectively. Among these subjects, sense of discrimination by skin color, captured 84 % of the association between African ancestry and major depression. CONCLUSION: SEP is an important effect modifier of the positive association between African ancestry and major depression. In addition, this association is predominantly mediated by the sense of feeling discriminated by skin color.
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População Negra/genética , Transtorno Depressivo Maior/etnologia , Estudos de Associação Genética , Genótipo , Adulto , Brasil , Transtorno Depressivo Maior/genética , Feminino , Humanos , Masculino , Prevalência , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
Partnership between early childhood development interventions and primary health care services can help catalyse health care uptake by socially vulnerable families. This study aimed to assess the real-life effects of a large-scale home visiting programme [Primeira Infância Melhor (PIM)] in Brazil on the use of preventive (prenatal visits, well child visits, dentist visits and vaccination) and recovery (emergency room visits and hospitalization) health services. A quasi-experiment nested in a population-based birth cohort study was conducted. The intervention group was firstly defined as all children enrolled in PIM up to age 6 months, and afterwards stratified between those enrolled during pregnancy or after birth up to 6 months. Children receiving PIM were matched with controls on propensity scores based on 27 confounders to estimate effects on health service use from prenatal to age 2 years. Double adjustment was applied in outcome Quasi-Poisson regressions. No evidence was found for effects of PIM starting anytime up to 6 months (262 pairs), or for the children enrolled only after birth (133 pairs), on outcomes occurring after age 6 months. When the programme started during pregnancy (129 pairs), there was a 13% higher prevalence of adequate prenatal visits (prevalence ratio = 1.13; 95% confidence interval 1.01-1.27), but no effect on use of any other health service. Sensitivity analyses suggested longer participation in the programme with reduced visitor turnover might improve its impact on prenatal visits. Integration between PIM and primary health care was not adequate to affect overall patterns of contacts with health services. Nevertheless, prenatal home visits showed potential to increase health service contact during a sensitive period of development, indicating the need to start such programmes before birth, when there is more time for maternal care, and family engagement in a network of services is facilitated.
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Desenvolvimento Infantil , Serviços de Saúde Materna , Gravidez , Criança , Feminino , Humanos , Pré-Escolar , Lactente , Brasil , Estudos de Coortes , Cuidado Pré-Natal , Visita DomiciliarRESUMO
BACKGROUND: The scale-up of parenting programmes to support early childhood development (ECD) is poorly understood. Little is known about how and when early interventions are most effective. Sustainability of ECD programming requires a better understanding of the mechanisms of real-world interventions. We examined the effects on caregiving practices of Primeira Infância Melhor (PIM), a state-wide home-visiting programme in Brazil. METHODS: This propensity score matched, longitudinal, quasiexperimental study uses data from the 2015 Pelotas Birth Cohort. We matched children who received PIM at any age with other cohort children on 25 key covariates. Sensitivity, guidance and responsiveness were assessed using video-recorded play tasks. Coerciveness and the parent-child relationship were assessed using the Parenting and Family Adjustment Scales. All parenting outcomes were examined at age 4 years. Separate moderation analyses were conducted for each effect modifier: family income, child age and duration of participation. RESULTS: Out of 4275 children in the cohort, 797 were enrolled in PIM up to age 4 years. 3018 children (70.6%) were included in the analytic sample, of whom 587 received PIM and 2431 were potential controls. We found a positive effect of PIM on responsiveness (ß=0.08, 95% CIs 0.002 to 0.16) and sensitivity (ß=0.10, 95% CIs 0.02 to 0.19). No effect was found for any secondary outcomes. Moderation analyses revealed a stronger positive effect on sensitivity for low-income parents (ß=0.18, 95% CIs 0.03 to 0.34). CONCLUSION: A state-wide, home-visiting programme in Brazil improved aspects of responsive caregiving. Effects were more pronounced for low-income families, suggesting benefits of purposeful targeting.
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Desenvolvimento Infantil , Poder Familiar , Humanos , Pré-Escolar , Brasil , PobrezaRESUMO
Background: Women's health and well-being (WHW) have been receiving growing attention, but limited progress has been made on how to measure its different domains in low- and middle-income countries (LMICs). We used data from five long-term birth cohorts in Brazil, Guatemala, the Philippines and South Africa to explore different domains of adult WHW, and how these domains relate to early life exposures. Methods: Based upon an a priori conceptualisation of eight postulated WHW outcomes available in the data, we grouped them as follows: human capital (intelligence quotient, schooling, height, and teenage childbearing), metabolic health (body mass index and metabolic syndrome score), and psychological (happiness and Self-Reported Questionnaire (SRQ) scores). Correlation analyses confirmed the variables theoretically belonging to the same dimension of WHW were statistically related. We then applied principal component analysis to each group of variables separately and used the first principal component as a summary quantitative measure of the corresponding WHW dimension. Finally, we assessed the association of each domain with a range of early-life factors: wealth, maternal education, maternal height, water, and sanitation, birthweight, length at two years and development quotient in mid-childhood. Results: The three domains were largely uncorrelated. Early determinants were positively associated with human capital, while birth order was negatively associated. Fewer associations were found for the metabolic or psychological components. Birthweight and weight at age two years were inversely associated with metabolic health. Maternal education was associated with better psychological health. Conclusions: Our findings indicate that WHW is multidimensional, with most women in the cohorts being compromised in one or more domains while few women scored highly in all three domains. Our analyses are limited by lack of data on adolescent exposures and on other relevant WHW dimensions such as safety, agency, empowerment, and violence. Further research is needed in LMICs for identifying and measuring the multiple domains of WHW.
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Países em Desenvolvimento , Saúde da Mulher , Humanos , Feminino , Adulto , Filipinas/epidemiologia , Brasil/epidemiologia , Guatemala , África do Sul , Coorte de Nascimento , Adolescente , Adulto Jovem , Estudos de Coortes , Fatores SocioeconômicosRESUMO
Maternal mental health during different stages of life can have a significant impact on a child's cognitive development. This study aimed to investigate the association between maternal CMD at two distinct stages of the offspring's life (at 3 months and 11 years) and their IQ scores at 6 and 18 years across two birth cohorts. The study utilized data from two Brazilian birth cohorts: the 1993 cohort (full sample: N = 3719, subsample: N = 436), and the 2004 Pelotas Birth Cohort (N = 3440). IQ assessments were conducted at ages 18 and 6, employing the Wechsler Adult Intelligence Scale, third version (WAIS-III), and Wechsler Intelligence Scale for Children, third version (WISC-III), respectively. The presence of maternal CMD at 3 months and 11 years of age was evaluated using the Brazilian version of the Self-Reporting Questionnaire (SRQ-20). After adjustment, participants whose mothers experienced CMD at 3 months had average IQ scores 1.74 (95 % CI: -2.83 to -0.67) and 2.79 (95 % CI: -5.54 to -0.04) points lower at ages 6 (2004 cohort) and 18 (1993 cohort subsample), respectively. Furthermore, in the 1993 cohort (both full and subsample), maternal CMD at 11 years was associated with lower IQ scores at age 18. Understanding the mechanisms underlying this association, emphasized by these findings, is crucial for promoting children's cognitive development, educational achievement, and overall well-being.
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Coorte de Nascimento , Saúde Mental , Criança , Feminino , Adulto , Humanos , Adolescente , Brasil/epidemiologia , Inteligência , Mães/psicologiaRESUMO
BACKGROUND: A large-scale parenting programme with weekly home visits (Primeira Infância Melhor (PIM)) has been implemented in the south of Brazil for nearly two decades, but lacks evaluation of its effects on early childhood development (ECD). This quasi-experimental study aimed to assess the effects of PIM in real-life settings within a population-based birth cohort study. METHODS: Data from the 2015 Pelotas Birth Cohort Study and the state programme information system were linked to identify study children who received PIM. Propensity score matching was used to create a comparable control group (using one-to-one matching) to estimate the effect of PIM on ECD measured at age 4 years. First, the impact of any enrolment in PIM was evaluated; then the intervention group was stratified according to whether enrolment occurred during pregnancy or after birth. Double adjustment was applied in linear regression to analyse child development scores, and Poisson regression for delayed development (below the 10th percentile of whole cohort). Effect modification due to family income was explored. RESULTS: There was no evidence that any enrolment in PIM (601 pairs) by age 4 years was associated with child development. However, PIM starting during pregnancy (estimated for 121 pairs) predicted higher development scores (0.27 SD; 95% CI 0.02 to 0.52), and 71% lower prevalence of delayed development (prevalence ratio=0.29; 95% CI 0.13 to 0.69), compared with the control group. There was strong statistical evidence (p=0.003, test of interaction) that the effect of PIM starting in pregnancy was larger than when starting after birth (480 pairs). The effect of PIM starting during pregnancy was found to be restricted to poorer families. CONCLUSIONS: In a real-life setting, PIM was effective only when starting during pregnancy and only for poorer families. A higher-quality programme might be more effective with a broader population.
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Coorte de Nascimento , Desenvolvimento Infantil , Brasil , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Poder Familiar , GravidezRESUMO
Studies leveraging gene-environment (GxE) interactions within Mendelian randomization (MR) analyses have prompted the emergence of two similar methodologies: MR-GxE and MR-GENIUS. Such methods are attractive in allowing for pleiotropic bias to be corrected when using individual instruments. Specifically, MR-GxE requires an interaction to be explicitly identified, while MR-GENIUS does not. We critically examine the assumptions of MR-GxE and MR-GENIUS in the absence of a pre-defined covariate, and propose sensitivity analyses to evaluate their performance. Finally, we explore the effect of body mass index (BMI) upon systolic blood pressure (SBP) using data from the UK Biobank, finding evidence of a positive effect of BMI on SBP. We find both approaches share similar assumptions, though differences between the approaches lend themselves to differing research settings. Where a suitable gene-by-covariate interaction is observed MR-GxE can produce unbiased causal effect estimates. MR-GENIUS can circumvent the need to identify interactions, but as a consequence relies on either the MR-GxE assumptions holding globally, or additional information with respect to the distribution of pleiotropic effects in the absence of an explicitly defined interaction covariate.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Viés , Pressão Sanguínea/genética , Índice de Massa Corporal , Causalidade , Análise da Randomização Mendeliana/métodosRESUMO
BACKGROUND: Two-sample Mendelian randomization (MR) allows the use of freely accessible summary association results from genome-wide association studies (GWAS) to estimate causal effects of modifiable exposures on outcomes. Some GWAS adjust for heritable covariables in an attempt to estimate direct effects of genetic variants on the trait of interest. One, both or neither of the exposure GWAS and outcome GWAS may have been adjusted for covariables. METHODS: We performed a simulation study comprising different scenarios that could motivate covariable adjustment in a GWAS and analysed real data to assess the influence of using covariable-adjusted summary association results in two-sample MR. RESULTS: In the absence of residual confounding between exposure and covariable, between exposure and outcome, and between covariable and outcome, using covariable-adjusted summary associations for two-sample MR eliminated bias due to horizontal pleiotropy. However, covariable adjustment led to bias in the presence of residual confounding (especially between the covariable and the outcome), even in the absence of horizontal pleiotropy (when the genetic variants would be valid instruments without covariable adjustment). In an analysis using real data from the Genetic Investigation of ANthropometric Traits (GIANT) consortium and UK Biobank, the causal effect estimate of waist circumference on blood pressure changed direction upon adjustment of waist circumference for body mass index. CONCLUSIONS: Our findings indicate that using covariable-adjusted summary associations in MR should generally be avoided. When that is not possible, careful consideration of the causal relationships underlying the data (including potentially unmeasured confounders) is required to direct sensitivity analyses and interpret results with appropriate caution.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Viés , Índice de Massa Corporal , Causalidade , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: Describing the prevalence of chronic diseases and associated socioeconomic and demographic factors, evaluating the patterns of social distancing and the antibodies prevalence against SARS-CoV-2 and COVID-19 symptoms in carriers and non-carriers of chronic diseases. METHODS: Data from 77,075 individuals aged 20 to 59 from three steps of the EPICOVID-19 Brazil (a nationwide serological survey conducted between May and June, 2021) were assessed. The presence of antibodies against SARS-CoV-2 was examined by rapid tests. Self-reported prevalence of hypertension, diabetes, asthma, cancer, chronic kidney disease and heart disease were investigated. The prevalence of mask use, adherence to isolation measures and antibodies were evaluated separately amid carriers and non-carriers of chronic diseases. The prevalence of symptoms was analyzed among carriers and non-carriers of chronic diseases with antibodies. RESULTS: The prevalence of at least one chronic disease was 43%, higher in the Southeast region, among white and indigenous individuals, women, less schooled and in lower socioeconomic position. The use of masks when leaving home was similar among carriers and non-carriers of chronic diseases (98%). The proportion of participants who reported adherence to isolation measures was higher amid carriers (15.9%) than non-carriers (24.9%) of chronic diseases. The prevalence of antibodies to SARS-CoV-2 was similar amongst carriers and non-carriers (2.4% and 2.3%). The prevalence of cough, dyspnea, palpitations and myalgia was significantly higher among carriers, but the proportion of symptomatic patients was similar between groups. CONCLUSION: The prevalence of chronic diseases in Brazil is high and the COVID-19 pandemic affects carriers and non-carriers of chronic diseases similarly. Carriers present more severe forms of COVID-19 and higher prevalence of symptoms. Greater adherence to social distancing measures among chronic patients is disassociated from a lower incidence of COVID-19 in this group.
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COVID-19 , Doenças não Transmissíveis , Brasil/epidemiologia , Feminino , Humanos , Pandemias , SARS-CoV-2RESUMO
This study aims to assess the association between mode of delivery and human capital among young adults enrolled in the 1982 and 1993 Pelotas birth cohorts, Rio Grande do Sul State, Brasil. In 1982 and 1993, the maternity hospitals of the municipality were daily visited, the births identified, and those live births, whose family lived in the urban area of Pelotas, were examined and their mothers interviewed. Information on mode of delivery, vaginal or cesarean, was provided by the mother in the perinatal study. Performance in intelligence tests achieved schooling and income were evaluated in the 30 years visit at the 1982 cohort. At the 1993 cohort, schooling and income were assessed at the 22 years visit, whereas IQ was evaluated at 18 years. Tobacco smoking in adulthood and type of school was used as negative outcomes to strength causal inference. Initially, cesarean section was positively associated with human capital at adulthood, with the exception of income in the 1993 cohort. After controlling for confounders, the magnitude of the associations was strongly reduced, and the regression coefficients were close to the null value. The negative outcome analysis showed that, after controlling for confounding variables, the mode of delivery was not associated with tobacco smoking and type of school. Suggesting that the variables included in the regression model to control for confounding, provided an adequate adjustment and it is unlikely that the results are due to residual confounding by socioeconomic status. On the other hand, considering the short- and long-term risks and the epidemic of cesarean sections, measures should be implemented to reduce its prevalence.