Assortative mating and within-spouse pair comparisons.

Spousal comparisons have been proposed as a design that can both reduce confounding and estimate effects of the shared adulthood environment. However, assortative mating, the process by which individuals select phenotypically (dis)similar mates, could distort associations when comparing spouses. We evaluated the use of spousal comparisons, as in the within-spouse pair (WSP) model, for aetiological research such as genetic association studies. We demonstrated that the WSP model can reduce confounding but may be susceptible to collider bias arising from conditioning on assorted spouse pairs. Analyses using UK Biobank spouse pairs found that WSP genetic association estimates were smaller than estimates from random pairs for height, educational attainment, and BMI variants. Within-sibling pair estimates, robust to demographic and parental effects, were also smaller than random pair estimates for height and educational attainment, but not for BMI. WSP models, like other within-family models, may reduce confounding from demographic factors in genetic association estimates, and so could be useful for triangulating evidence across study designs to assess the robustness of findings. However, WSP estimates should be interpreted with caution due to potential collider bias.

Effects of early-life poverty on health and human capital in children and adolescents: analyses of national surveys and birth cohort studies in LMICs.

The survival and nutrition of children and, to a lesser extent, adolescents have improved substantially in the past two decades. Improvements have been linked to the delivery of effective biomedical, behavioural, and environmental interventions; however, large disparities exist between and within countries. Using data from 95 national surveys in low-income and middle-income countries (LMICs), we analyse how strongly the health, nutrition, and cognitive development of children and adolescents are related to early-life poverty. Additionally, using data from six large, long-running birth cohorts in LMICs, we show how early-life poverty can have a lasting effect on health and human capital throughout the life course. We emphasise the importance of implementing multisectoral anti-poverty policies and programmes to complement specific health and nutrition interventions delivered at an individual level, particularly at a time when COVID-19 continues to disrupt economic, health, and educational gains achieved in the recent past.

Health and development from preconception to 20 years of age and human capital.

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5-19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood.

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits.

Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E-04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E-03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E-06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.

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.

Geographic inequalities in health intervention coverage - mapping the composite coverage index in Peru using geospatial modelling.

BACKGROUND: The composite coverage index (CCI) provides an integrated perspective towards universal health coverage in the context of reproductive, maternal, newborn and child health. Given the sample design of most household surveys does not provide coverage estimates below the first administrative level, approaches for achieving more granular estimates are needed. We used a model-based geostatistical approach to estimate the CCI at multiple resolutions in Peru. METHODS: We generated estimates for the eight indicators on which the CCI is based for the departments, provinces, and areas of 5 × 5 km of Peru using data from two national household surveys carried out in 2018 and 2019 plus geospatial covariates. Bayesian geostatistical models were fit using the INLA-SPDE approach. We assessed model fit using cross-validation at the survey cluster level and by comparing modelled and direct survey estimates at the department-level. RESULTS: CCI coverage in the provinces along the coast was consistently higher than in the remainder of the country. Jungle areas in the north and east presented the lowest coverage levels and the largest gaps between and within provinces. The greatest inequalities were found, unsurprisingly, in the largest provinces where populations are scattered in jungle territory and are difficult to reach. CONCLUSIONS: Our study highlighted provinces with high levels of inequality in CCI coverage indicating areas, mostly low-populated jungle areas, where more attention is needed. We also uncovered other areas, such as the border with Bolivia, where coverage is lower than the coastal provinces and should receive increased efforts. More generally, our results make the case for high-resolution estimates to unveil geographic inequities otherwise hidden by the usual levels of survey representativeness.

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.

Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.

Patterns of Growth in Childhood in Relation to Adult Schooling Attainment and Intelligence Quotient in 6 Birth Cohorts in Low- and Middle-Income Countries: Evidence from the Consortium of Health-Oriented Research in Transitioning Societies (COHORTS).

BACKGROUND: Growth faltering has been associated with poor intellectual performance. The relative strengths of associations between growth in early and in later childhood remain underexplored. OBJECTIVES: We examined the association between growth in childhood and adult human capital in 5 low- and middle-income countries (LMICs). METHODS: We analyzed data from 9503 participants in 6 prospective birth cohorts from 5 LMICs (Brazil, Guatemala, India, the Philippines, and South Africa). We used linear and quasi-Poisson regression models to assess the associations between measures of height and relative weight at 4 age intervals [birth, age ∼2 y, midchildhood (MC), adulthood] and 2 dimensions of adult human capital [schooling attainment and Intelligence Quotient (IQ)]. RESULTS: Meta-analysis of site- and sex-specific estimates showed statistically significant associations between size at birth and height at ∼2 y and the 2 outcomes (P < 0.001). Weight and length at birth and linear growth from birth to ∼2 y of age (1 z-score difference) were positively associated with schooling attainment (ß: 0.13; 95% CI: 0.08, 0.19, ß: 0.17; 95% CI: 0.07, 0.32, and ß: 0.25, 95% CI: 0.10, 0.40, respectively) and adult IQ (ß: 0.74, 95% CI: 0.35, 1.14, ß: 0.73, 95% CI: 0.35, 1.10, and ß: 1.52, 95% CI: 0.96, 2.08, respectively). Linear growth from age 2 y to MC and from MC to adulthood was not associated with higher school attainment or IQ. Change in relative weight in early childhood, MC, and adulthood was not associated with either outcome. CONCLUSIONS: Linear growth in the first 1000 d is a predictor of schooling attainment and IQ in adulthood in LMICs. Linear growth in later periods was not associated with either of these outcomes. Changes in relative weight across the life course were not associated with schooling and IQ in adulthood.

Slow Spread of SARS-CoV-2 in Southern Brazil Over a 6-Month Period: Report on 8 Sequential Statewide Serological Surveys Including 35 611 Participants.

Objectives. To evaluate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over 6 months in the Brazilian State of Rio Grande do Sul (population 11.3 million), based on 8 serological surveys. Methods. In each survey, 4151 participants in round 1 and 4460 participants in round 2 were randomly sampled from all state regions. We assessed presence of antibodies against SARS-CoV-2 using a validated lateral flow point-of-care test; we adjusted figures for the time-dependent decay of antibodies. Results. The SARS-CoV-2 antibody prevalence increased from 0.03% (95% confidence interval [CI] = 0.00%, 0.34%; 1 in every 3333 individuals) in mid-April to 1.89% (95% CI = 1.36%, 2.54%; 1 in every 53 individuals) in early September. Prevalence was similar across gender and skin color categories. Older adults were less likely to be infected than younger participants. The proportion of the population who reported leaving home daily increased from 21.4% (95% CI = 20.2%, 22.7%) to 33.2% (95% CI = 31.8%, 34.5%). Conclusions. SARS-CoV-2 infection increased slowly during the first 6 months in the state, differently from what was observed in other Brazilian regions. Future survey rounds will continue to document the spread of the pandemic.

[Prevalence of antibodies against SARS-CoV-2 according to socioeconomic and ethnic status in a nationwide Brazilian surveyPrevalência de anticorpos contra o SARS-CoV-2 de acordo com o status socioeconômico e étnico em uma pesquisa nacional no Brasil]. / Prevalencia de anticuerpos contra el SARS-CoV-2 según el estatus socioeconómico y étnico en una encuesta nacional de Brasil.

OBJECTIVES: To investigate socioeconomic and ethnic group inequalities in prevalence of antibodies against SARS-CoV-2 in the 27 federative units of Brazil. METHODS: In this cross-sectional study, three household surveys were carried out on May 14-21, June 4-7, and June 21-24, 2020 in 133 Brazilian urban areas. Multi-stage sampling was used to select 250 individuals in each city to undergo a rapid antibody test. Subjects answered a questionnaire on household assets, schooling and self-reported skin color/ethnicity using the standard Brazilian classification in five categories: white, black, brown, Asian or indigenous. Principal component analyses of assets was used to classify socioeconomic position into five wealth quintiles. Poisson regression was used for the analyses. RESULTS: 25 025 subjects were tested in the first, 31 165 in the second, and 33 207 in the third wave of the survey, with prevalence of positive results equal to 1.4%, 2.4%, and 2.9% respectively. Individuals in the poorest quintile were 2.16 times (95% confidence interval 1.86; 2.51) more likely to test positive than those in the wealthiest quintile, and those with 12 or more years of schooling had lower prevalence than subjects with less education. Indigenous individuals had 4.71 (3.65; 6.08) times higher prevalence than whites, as did those with black or brown skin color. Adjustment for region of the country reduced the prevalence ratios according to wealth, education and ethnicity, but results remained statistically significant. CONCLUSIONS: The prevalence of antibodies against SARS-CoV-2 in Brazil shows steep class and ethnic gradients, with lowest risks among white, educated and wealthy individuals.

OBJETIVOS: Investigar as desigualdades socioeconômicas e étnicas na prevalência de anticorpos contra SARS-CoV-2 nas 27 unidades federativas do Brasil. MÉTODOS: Neste estudo transversal, três pesquisas domiciliares foram realizadas de 14 a 21 de maio, 4 a 7 de junho, e 21-24 de junho, 2020 em 133 áreas urbanas brasileiras. Amostragem em várias etapas foi utilizada para selecionar 250 indivíduos em cada cidade para se submeter a um teste rápido de anticorpos. Os sujeitos responderam a um questionário sobre bens domésticos, escolaridade e cor da pele/etnicidade (auto-relatada utilizando a classificação padrão brasileira de cinco categorias: branco, preto, pardo, asiático ou indígena). A análise dos componentes principais dos ativos foi utilizada para classificar a posição socioeconómica em cinco quintis de riqueza. A regressão de Poisson foi utilizada para as análises. RESULTADOS: 25 025 indivíduos foram testados na primeira pesquisa, 31 165 na segunda, e 33 207 na terceira, com prevalência de resultados positivos de 1,4%, 2,4% e 2,9%, respectivamente. Indivíduos no quintil mais pobre tinham 2,16 vezes (intervalo de confiança de 95% 1,86; 2,51) mais probabilidade de ter um resultado positivo do que aqueles do quintil mais rico, e aqueles com 12 ou mais anos de escolaridade tinham uma prevalência menor do que aqueles com menos educação. Os indivíduos indígenas tinham 4,71 (3,65; 6,08) vezes mais prevalência do que os brancos, assim como aqueles com cor da pele preta ou parda. O ajuste regional reduziu as taxas de prevalência de acordo com a riqueza, educação e etnia, mas os resultados permaneceram estatisticamente significativos. CONCLUSÕES: A prevalência de anticorpos contra a SARS-CoV-2 no Brasil mostra gradientes relacionados com a posição socioeconómica e a etnia muito acentuados, com os menores riscos entre os indivíduos brancos, educados e ricos.

Geospatial estimation of reproductive, maternal, newborn and child health indicators: a systematic review of methodological aspects of studies based on household surveys.

BACKGROUND: Geospatial approaches are increasingly used to produce fine spatial scale estimates of reproductive, maternal, newborn and child health (RMNCH) indicators in low- and middle-income countries (LMICs). This study aims to describe important methodological aspects and specificities of geospatial approaches applied to RMNCH coverage and impact outcomes and enable non-specialist readers to critically evaluate and interpret these studies. METHODS: Two independent searches were carried out using Medline, Web of Science, Scopus, SCIELO and LILACS electronic databases. Studies based on survey data using geospatial approaches on RMNCH in LMICs were considered eligible. Studies whose outcomes were not measures of occurrence were excluded. RESULTS: We identified 82 studies focused on over 30 different RMNCH outcomes. Bayesian hierarchical models were the predominant modeling approach found in 62 studies. 5 × 5 km estimates were the most common resolution and the main source of information was Demographic and Health Surveys. Model validation was under reported, with the out-of-sample method being reported in only 56% of the studies and 13% of the studies did not present a single validation metric. Uncertainty assessment and reporting lacked standardization, and more than a quarter of the studies failed to report any uncertainty measure. CONCLUSIONS: The field of geospatial estimation focused on RMNCH outcomes is clearly expanding. However, despite the adoption of a standardized conceptual modeling framework for generating finer spatial scale estimates, methodological aspects such as model validation and uncertainty demand further attention as they are both essential in assisting the reader to evaluate the estimates that are being presented.

Prevalence of antibodies against SARS-CoV-2 according to socioeconomic and ethnic status in a nationwide Brazilian survey.

OBJECTIVES: To investigate socioeconomic and ethnic group inequalities in prevalence of antibodies against SARS-CoV-2 in the 27 federative units of Brazil. METHODS: In this cross-sectional study, three household surveys were carried out on May 14-21, June 4-7, and June 21-24, 2020 in 133 Brazilian urban areas. Multi-stage sampling was used to select 250 individuals in each city to undergo a rapid antibody test. Subjects answered a questionnaire on household assets, schooling and self-reported skin color/ethnicity using the standard Brazilian classification in five categories: white, black, brown, Asian or indigenous. Principal component analyses of assets was used to classify socioeconomic position into five wealth quintiles. Poisson regression was used for the analyses. RESULTS: 25 025 subjects were tested in the first, 31 165 in the second, and 33 207 in the third wave of the survey, with prevalence of positive results equal to 1.4%, 2.4%, and 2.9% respectively. Individuals in the poorest quintile were 2.16 times (95% confidence interval 1.86; 2.51) more likely to test positive than those in the wealthiest quintile, and those with 12 or more years of schooling had lower prevalence than subjects with less education. Indigenous individuals had 4.71 (3.65; 6.08) times higher prevalence than whites, as did those with black or brown skin color. Adjustment for region of the country reduced the prevalence ratios according to wealth, education and ethnicity, but results remained statistically significant. CONCLUSIONS: The prevalence of antibodies against SARS-CoV-2 in Brazil shows steep class and ethnic gradients, with lowest risks among white, educated and wealthy individuals.

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

A Genome-Wide Association Study in Hispanics/Latinos Identifies Novel Signals for Lung Function. The Hispanic Community Health Study/Study of Latinos.

RATIONALE: Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry. OBJECTIVES: Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations. METHODS: GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies. MEASUREMENTS AND MAIN RESULTS: Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for FEV1 in ZSWIM7 (rs4791658; P = 4.99 × 10-9) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with FEV1/FVC (P = 9.59 × 10-9) in a region previously identified for COPD-related phenotypes; it remained significant in conditional analyses but did not replicate. Admixture mapping identified a novel region, with a variant in AGMO (rs41331850), associated with Amerindian ancestry and FEV1, which replicated. A novel locus for FEV1 identified among ever smokers (rs291231; P = 1.92 × 10-8) approached statistical significance for replication in admixed populations of African ancestry, and a novel SNP for COPD in PDZD2 (rs7709630; P = 1.56 × 10-8) regionally replicated. In addition, loci previously identified for lung function in European samples were associated in Hispanic/Latino participants in the Hispanic Community Health Study/Study of Latinos at the genome-wide significance level. CONCLUSIONS: We identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing to genetic etiologies of COPD.

African ancestry, lung function and the effect of genetics.

African-Americans have smaller lung function compared with European-Americans. The aim of this study was to disentangle the contribution of genetics from other variables on lung function. A cohort was followed from birth to 30 years of age in Brazil. Several variables were collected: genomic analysis based on DNA; forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) obtained by spirometry; height measured by anthropometrists; and thorax circumference evaluated by photonic scanner. Crude and adjusted linear regression models were calculated according to African ancestry. The sample comprised 2869 participants out of 3701 members of the cohort. Males with higher African ancestry by DNA analysis had a smaller FEV1 (-0.13 L, 95% CI -0.23- -0.03 L) and FVC (-0.21 L, 95% CI -0.32- -0.09 L) compared with those with less African ancestry, having accounted for height, sitting to standing height ratio and other confounders. Similar effects were seen in females. After adjustment, ancestry remained significantly associated with lung function, but the large effect of adjustment for confounding among males (but not females) does not allow us to exclude the possibility that residual confounding may still account for these findings.

Ewing Sarcoma: influence of TP53 Arg72Pro and MDM2 T309G SNPs.

The Ewing Sarcoma is an important tumor of bone and soft tissue. The SNPs Arg72Pro of TP53 and T309G of MDM2 have been associated with many cancer types and have been differently distributed among populations worldwide. Based on a case-control design, this study aimed to assess the role of these SNPs in 24 Ewing Sarcoma patients, compared to 91 control individuals. DNA samples were extracted from blood and genotyped for both SNPs by PCR-RFLP and confirmed by DNA sequencing. The results showed an association between the G allele of the T309G and Ewing Sarcoma (P=0.02). Comparing to the TT carriers, the risk of G allele carriers was 3.35 (95% CI=1.22-9.21) with P=0.02. At the genotypic level, an association of the TT genotype with the control group (P=0.03) was found. Comparing to the TT genotype, the risk of TG and GG was 2.97 (95% CI=1.03-8.58) with P=0.04 and 5.00 (95% CI=1.23-20.34) with P=0.02, respectively. No associations regarding the Arg72Pro SNP were found. Considering that the T309G has been associated with several types of cancer, including sarcomas, our results indicate that this SNP may also be important to Ewing Sarcoma predisposition.

Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci.

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: "Some College" (yes/no, for any education beyond high school) and "Graduated College" (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10-8) and suggestive (p < 1 × 10-6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

COVID-19 and outpatient care: a nationwide household survey.

We aimed to assess the proportion of the population in 133 Brazilian municipalities who - from March to August 2020 - had a health problem but failed to seek care or failed to attend to a health service for routine appointment or examination. We conducted a household survey from August 24-27 in 133 Brazilian cities by asking the subjects if, since the beginning of the COVID-19 pandemic in March 2020, they had suffered from a health problem but did not seek care or failed to attend to a routine or screening examination. Poisson regression was used for the analyses. We interviewed 33,250 subjects and 11.8% (95%CI: 11.4-12.1) reported that, since March 2020, they failed to seek care despite being ill, 17.3% (95%CI: 16.9-17.7) failed to attend to a routine or screening examination and 23.9% (95%CI: 23.4-24.4) reported one or both outcomes. Health service closure and fear of the COVID-19 infection were the main reasons for not seeking care. Women and the poorest were more likely to not look for a health service, despite having a health problem or a scheduled routine appointment. On the other hand, those subjects who self-identified as white were less likely to not look for a health service. The COVID-19 pandemic is more critical for the indigenous people and the poorest, and these people are also more likely to not seek care for other health conditions during the pandemic.

[Mask use during the COVID-19 pandemic in Brazil: results of the EPICOVID19-BR study]. / Uso de máscara durante a pandemia de COVID-19 no Brasil: resultados do estudo EPICOVID19-BR.

By March 3, 2022, the COVID-19 pandemic has caused more than 399 million infections and claimed the lives of more than five million people worldwide. To reduce infection rates, a series of prevention measures indicated by the World Health Organization (WHO) were adopted by countries, including the use of masks. This study aims to describe mask use in Brazil via data analysis from the EPICOVID19-BR, a population-based study conducted in 133 cities in the country in four phases between March and August 2020. The proportion of individuals who reported wearing a mask when they left their homes was 97.9% (95%CI: 97.8-98.0). The interviewer did not see interviewees' mask in 50% (95%CI: 49.9-51.1) of the cases at the time of the interview. However, between phase one and four of the survey, we observed a 4.4% decrease in the proportion of interviewees who failed to wear masks at the time of the interview. Mask non-visualization was more prominent in women, participants aged 10-19 and 20-29 years of indigenous, black, and brown skin color, and those with elementary and high school education and in the Central-West Region. The use of cloth masks showed a 91.4% predominance (95%CI: 91.2-1.5) with a 4.9% increase between phases 1 and 4. The results of the study bring important information to reinforce COVID-19 control policies in Brazil. The high percentage of people who failed to wear masks at the time of the interview suggests that it is still important to reinforce prevention and self-care, rather than relating mask wear to a mandatory measure.

A pandemia de COVID-19 já causou mais de 399 milhões de infecções e custou a vida de mais de cinco milhões de pessoas no mundo, até 3 de março de 2022. Para reduzir a taxa de infecção, uma série de medidas de prevenção indicadas pela Organização Mundial da Saúde (OMS) foram adotadas pelos países, entre elas, o uso de máscara. O objetivo deste estudo é descrever a utilização de máscara na população brasileira, através da análise de dados do EPICOVID19-BR, um estudo de base populacional realizado em 133 cidades do país, em quatro fases entre março e agosto de 2020. A proporção de indivíduos que preferiram usar máscara quando saíam de casa foi de 97,9% (IC95%: 97,8-98,0). O entrevistador não visualizou a máscara do entrevistado em 50% (IC95%: 49,9-51,1) dos casos no momento da entrevista, no entanto, entre a fase uma e quatro da pesquisa, observou-se uma diminuição de 4,4 pontos percentuais na proporção de entrevistados que não usaram máscara no momento da entrevista. A não visualização da máscara foi mais observada em mulheres, participantes com idade entre 10-19 e 20-29 anos, de cor de pele indígena, preta, e parda, entre as pessoas com Ensinos Fundamental e Médio e na Região Centro-oeste. O uso de máscara de tecido foi predominante 91,4% (IC95%: 91,2-91,5) com um aumento de 4,9 pontos percentuais entre as fases 1 e 4. Os resultados do estudo trazem informações importantes para reforçar as políticas de controle de COVID-19 no Brasil. O alto percentual de pessoas sem máscara na hora da entrevista sugere que ainda é importante reforçar o aspecto preventivo e de autocuidado, não fazendo do uso da máscara algo apenas ligado à obrigatoriedade.

La pandemia del COVID-19 ha provocado más de 399 millones de infecciones y se ha cobrado la vida de más de cinco millones de personas en todo el mundo hasta el 3 de Marzo de 2022. Para reducir la tasa de contagios, los países adoptaron una serie de medidas de prevención indicadas por la Organización Mundial de la Salud (OMS), entre ellas el uso de mascarillas. El objetivo de este estudio es describir el uso de mascarillas en la población brasileña, utilizando el análisis de datos de EPICOVID19-BR, un estudio de base poblacional realizado en 133 ciudades del país, en cuatro fases entre marzo y agosto de 2020. La proporción de personas que informaron usar mascarillas al salir de casa fue del 97,9% (IC95%: 97,8-98,0). El entrevistador no vio la mascarilla del entrevistado en el 50% (IC95%: 49,9-51,1) de los casos al momento de la entrevista, sin embargo entre las fases uno y cuatro de la investigación se observó una disminución de 4,4 puntos porcentuales en la proporción de los encuestados que no llevaban mascarilla durante la entrevista. Se observó una mayor visualización de falta de uso de mascarillas en las mujeres, en participantes con edades entre 10-19 y 20-29 años, de color de piel indígena, negra y parda, entre personas con educación primaria y secundaria y en la Región Centro-oeste. Hubo un mayor predominio de uso de mascarillas de tela en el 91,4% (IC95%: 91,2-91,5) con un aumento de 4,9 puntos porcentuales entre las fases 1 y 4. Los resultados muestran la importancia de fortalecer las políticas de prevención del COVID-19 en Brasil. El alto porcentaje de personas sin mascarilla al momento de la entrevista sugiere que es importante reforzar la prevención y el autocuidado en general no solo relacionado a la obligatoriedad en el uso de mascarillas.