A multi-ethnic reference panel to impute HLA classical and non-classical class I alleles in admixed samples: Testing imputation accuracy in an admixed sample from Brazil.

The MHC class I region contains crucial genes for the innate and adaptive immune response, playing a key role in susceptibility to many autoimmune and infectious diseases. Genome-wide association studies have identified numerous disease-associated SNPs within this region. However, these associations do not fully capture the immune-biological relevance of specific HLA alleles. HLA imputation techniques may leverage available SNP arrays by predicting allele genotypes based on the linkage disequilibrium between SNPs and specific HLA alleles. Successful imputation requires diverse and large reference panels, especially for admixed populations. This study employed a bioinformatics approach to call SNPs and HLA alleles in multi-ethnic samples from the 1000 genomes (1KG) dataset and admixed individuals from Brazil (SABE), utilising 30X whole-genome sequencing data. Using HIBAG, we created three reference panels: 1KG (n = 2504), SABE (n = 1171), and the full model (n = 3675) encompassing all samples. In extensive cross-validation of these reference panels, the multi-ethnic 1KG reference exhibited overall superior performance than the reference with only Brazilian samples. However, the best results were achieved with the full model. Additionally, we expanded the scope of imputation by developing reference panels for non-classical, MICA, MICB and HLA-H genes, previously unavailable for multi-ethnic populations. Validation in an independent Brazilian dataset showcased the superiority of our reference panels over the Michigan Imputation Server, particularly in predicting HLA-B alleles among Brazilians. Our investigations underscored the need to enhance or adapt reference panels to encompass the target population's genetic diversity, emphasising the significance of multiethnic references for accurate imputation across different populations.

Optimal population-specific HLA imputation with dimension reduction.

Human genomics has quickly evolved, powering genome-wide association studies (GWASs). SNP-based GWASs cannot capture the intense polymorphism of HLA genes, highly associated with disease susceptibility. There are methods to statistically impute HLA genotypes from SNP-genotypes data, but lack of diversity in reference panels hinders their performance. We evaluated the accuracy of the 1000 Genomes data as a reference panel for imputing HLA from admixed individuals of African and European ancestries, focusing on (a) the full dataset, (b) 10 replications from 6 populations, and (c) 19 conditions for the custom reference panels. The full dataset outperformed smaller models, with a good F1-score of 0.66 for HLA-B. However, custom models outperformed the multiethnic or population models of similar size (F1-scores up to 0.53, against up to 0.42). We demonstrated the importance of using genetically specific models for imputing populations, which are currently underrepresented in public datasets, opening the door to HLA imputation for every genetic population.

Characterization of pharmacogenomic variants in a Brazilian admixed cohort of elderly individuals based on whole-genome sequencing data.

Introduction: Research in the field of pharmacogenomics (PGx) aims to identify genetic variants that modulate response to drugs, through alterations in their pharmacokinetics (PK) or pharmacodynamics (PD). The distribution of PGx variants differs considerably among populations, and whole-genome sequencing (WGS) plays a major role as a comprehensive approach to detect both common and rare variants. This study evaluated the frequency of PGx markers in the context of the Brazilian population, using data from a population-based admixed cohort from Sao Paulo, Brazil, which includes variants from WGS of 1,171 unrelated, elderly individuals. Methods: The Stargazer tool was used to call star alleles and structural variants (SVs) from 38 pharmacogenes. Clinically relevant variants were investigated, and the predicted drug response phenotype was analyzed in combination with the medication record to assess individuals potentially at high-risk of gene-drug interaction. Results: In total, 352 unique star alleles or haplotypes were observed, of which 255 and 199 had a frequency < 0.05 and < 0.01, respectively. For star alleles with frequency > 5% (n = 97), decreased, loss-of-function and unknown function accounted for 13.4%, 8.2% and 27.8% of alleles or haplotypes, respectively. Structural variants (SVs) were identified in 35 genes for at least one individual, and occurred with frequencies >5% for CYP2D6, CYP2A6, GSTM1, and UGT2B17. Overall 98.0% of the individuals carried at least one high risk genotype-predicted phenotype in pharmacogenes with PharmGKB level of evidence 1A for drug interaction. The Electronic Health Record (EHR) Priority Result Notation and the cohort medication registry were combined to assess high-risk gene-drug interactions. In general, 42.0% of the cohort used at least one PharmGKB evidence level 1A drug, and 18.9% of individuals who used PharmGKB evidence level 1A drugs had a genotype-predicted phenotype of high-risk gene-drug interaction. Conclusion: This study described the applicability of next-generation sequencing (NGS) techniques for translating PGx variants into clinically relevant phenotypes on a large scale in the Brazilian population and explores the feasibility of systematic adoption of PGx testing in Brazil.

Challenges in selecting admixture models and marker sets to infer genetic ancestry in a Brazilian admixed population.

The inference of genetic ancestry plays an increasingly prominent role in clinical, population, and forensic genetics studies. Several genotyping strategies and analytical methodologies have been developed over the last few decades to assign individuals to specific biogeographic regions. However, despite these efforts, ancestry inference in populations with a recent history of admixture, such as those in Brazil, remains a challenge. In admixed populations, proportion and components of genetic ancestry vary on different levels: (i) between populations; (ii) between individuals of the same population, and (iii) throughout the individual's genome. The present study evaluated 1171 admixed Brazilian samples to compare the genetic ancestry inferred by tri-/tetra-hybrid admixture models and evaluated different marker sets from those with small numbers of ancestry informative markers panels (AIMs), to high-density SNPs (HDSNP) and whole-genome-sequence (WGS) data. Analyses revealed greater variation in the correlation coefficient of ancestry components within and between admixed populations, especially for minority ancestral components. We also observed positive correlation between the number of markers in the AIMs panel and HDSNP/WGS. Furthermore, the greater the number of markers, the more accurate the tri-/tetra-hybrid admixture models.

Whole-genome sequencing of 1,171 elderly admixed individuals from São Paulo, Brazil.

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS.

HLA-G genetic diversity and evolutive aspects in worldwide populations.

HLA-G is a promiscuous immune checkpoint molecule. The HLA-G gene presents substantial nucleotide variability in its regulatory regions. However, it encodes a limited number of proteins compared to classical HLA class I genes. We characterized the HLA-G genetic variability in 4640 individuals from 88 different population samples across the globe by using a state-of-the-art method to characterize polymorphisms and haplotypes from high-coverage next-generation sequencing data. We also provide insights regarding the HLA-G genetic diversity and a resource for future studies evaluating HLA-G polymorphisms in different populations and association studies. Despite the great haplotype variability, we demonstrated that: (1) most of the HLA-G polymorphisms are in introns and regulatory sequences, and these are the sites with evidence of balancing selection, (2) linkage disequilibrium is high throughout the gene, extending up to HLA-A, (3) there are few proteins frequently observed in worldwide populations, with lack of variation in residues associated with major HLA-G biological properties (dimer formation, interaction with leukocyte receptors). These observations corroborate the role of HLA-G as an immune checkpoint molecule rather than as an antigen-presenting molecule. Understanding HLA-G variability across populations is relevant for disease association and functional studies.

Methodological Description of Mapping Brazilian Long-Term Care Facilities for Older Adults / Descrição Metodológica do Mapeamento das Instituições de Longa-Permanência para Idosos no Brasil

Aim: describe the methodological approach adopted to build a Brazilian database of LCTFs in the country. Methods: This exploratory research was conducted between August 2020 and 2021 based on primarily publicly accessible data. First, the database of the Sistema Único de Assistência Social for 2019 was adopted as the primary source of information. In addition, public agencies and managers were consulted and invited to share their databases. Likewise, researchers and private entities also collaborated by making their spreadsheets available. The information collected was placed in individual spreadsheets for each Brazilian state. LTCFs not catering to older adults (aged 60 and over) were excluded. Duplicate data were excluded when overlaps were identified for each new aggregated source. Results & Discussion: This brief communication describes the methodology adopted for mapping the current status of Brazilian LTCFs. Despite its caveats, this study represents an important advance in the identification, characterization, and monitoring of these services nationwide. A total of 5769 facilities were found in the 2019 SUAS census. After excluding facilities not caring for residents aged 60 or over, this total decreased to 2381 LTCFs. Consolidating and filtering the information from multiple data sources led to the identification of 7029 LTCFs for the country as a whole.

Biased pathogenic assertions of loss of function variants challenge molecular diagnosis of admixed individuals.

Diagnosis of individuals affected by monogenic disorders was significantly improved by next-generation sequencing targeting clinically relevant genes. Whole exomes yield a large number of variants that require several filtering steps, prioritization, and pathogenicity classification. Among the criteria recommended by ACMG, those that rely on population databases critically affect analyses of individuals with underrepresented ancestries. Population-specific allelic frequencies need consideration when characterizing potential deleteriousness of variants. An orthogonal input for classification is annotation of variants previously classified as pathogenic as a criterion that provide supporting evidence widely sourced at ClinVar. We used a whole-genome dataset from a census-based cohort of 1,171 elderly individuals from São Paulo, Brazil, highly admixed, and unaffected by severe monogenic disorders, to investigate if pathogenic assertions in ClinVar are enriched with higher proportions of European ancestry, indicating bias. Potential loss of function (pLOF) variants were filtered from 4,250 genes associated with Mendelian disorders and annotated with ClinVar assertions. Over 1,800 single nucleotide pLOF variants were included, 381 had non-benign assertions. Among carriers (N = 463), average European ancestry was significantly higher than noncarriers (N = 708; p = .011). pLOFs in genomic contexts of non-European local ancestries were nearly three times less likely to have any ClinVar entry (OR = 0.353; p <.0001). Independent pathogenicity assertions are useful for variant classification in molecular diagnosis. However, European overrepresentation of assertions can promote distortions when classifying variants in non-European individuals, even in admixed samples with a relatively high proportion of European ancestry. The investigation and deposit of clinically relevant findings of diverse populations is fundamental improve this scenario.

Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass and fat mass indexes.

BACKGROUND/OBJECTIVES: Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely underrepresented in genomic studies. Here, we study the genetic architecture of BMI in children, young adults, and elderly individuals from the admixed population of Brazil. SUBJECTS/METHODS: Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European, and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of body mass index (BMI) in three Brazilian population-based cohorts from Northeast (Salvador), Southeast (Bambuí), and South (Pelotas). RESULTS: We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p = 2.76e-06). This variant is rare in Europeans but with frequencies of ~3% in West Africa and has a strong female-specific effect (95% CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among women with morbid obesity from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five times higher than the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects. CONCLUSIONS: We identified six candidate SNPs associated with BMI. rs114066381 stands out for its high effect that was replicated and its high frequency in women with morbid obesity. We demonstrate how admixed populations are a source of new relevant phenotype-associated genetic variants.

Structural variation of the malaria-associated human glycophorin A-B-E region.

BACKGROUND: Approximately 5% of the human genome shows common structural variation, which is enriched for genes involved in the immune response and cell-cell interactions. A well-established region of extensive structural variation is the glycophorin gene cluster, comprising three tandemly-repeated regions about 120 kb in length and carrying the highly homologous genes GYPA, GYPB and GYPE. Glycophorin A (encoded by GYPA) and glycophorin B (encoded by GYPB) are glycoproteins present at high levels on the surface of erythrocytes, and they have been suggested to act as decoy receptors for viral pathogens. They are receptors for the invasion of the protist parasite Plasmodium falciparum, a causative agent of malaria. A particular complex structural variant, called DUP4, creates a GYPB-GYPA fusion gene known to confer resistance to malaria. Many other structural variants exist across the glycophorin gene cluster, and they remain poorly characterised. RESULTS: Here, we analyse sequences from 3234 diploid genomes from across the world for structural variation at the glycophorin locus, confirming 15 variants in the 1000 Genomes project cohort, discovering 9 new variants, and characterising a selection of these variants using fibre-FISH and breakpoint mapping at the sequence level. We identify variants predicted to create novel fusion genes and a common inversion duplication variant at appreciable frequencies in West Africans. We show that almost all variants can be explained by non-allelic homologous recombination and by comparing the structural variant breakpoints with recombination hotspot maps, confirm the importance of a particular meiotic recombination hotspot on structural variant formation in this region. CONCLUSIONS: We identify and validate large structural variants in the human glycophorin A-B-E gene cluster which may be associated with different clinical aspects of malaria.

Gender Differences in the Incidence and Determinants of Components of the Frailty Phenotype Among Older Adults: Findings From the SABE Study.

OBJECTIVE: To analyze gender differences in incidence and determinants of the components of the frailty phenotype. METHOD: A total of 1,413 older adults were selected in 2006. To estimate the incidence of each frailty component, only individuals who did not exhibit a given component at baseline (independently of the presence of other components) were included in the study. The variables of interest were socioeconomic, behavioral, clinical, anthropometric factors and physical performance. The incidence of each component in 2010 was the outcome. RESULTS: Unintentional weight loss and slowness were more incident in men up to 74 years of age. The other frailty components were more incident in women at all age groups, except weakness. Besides age, the determinants of incidence of the components of frailty were different between genders. DISCUSSION: Strategies for preventing or delaying the installation of frailty need to address gender differences, considering the greater complexity in the network determinants among women.

Female double incontinence: prevalence, incidence, and risk factors from the SABE (Health, Wellbeing and Aging) study.

INTRODUCTION AND HYPOTHESIS: Double Incontinence (DI) is incontinence of urine and stool and is an extreme manifestation of pelvic floor dysfunction. The objective of this study was to estimate the prevalence and incidence of DI and the risk factors in elderly women in São Paulo, Brazil. METHODS: This was a prospective study in women aged 65 years or older evaluated in 2006 and re-evaluated in 2010. The sample was selected by two-phase stratified sampling with replacement and probability proportional to size. The likelihood ratio test was performed and Cox regression curves were generated to evaluate the equality of survival. Poisson's regression was used to evaluate risk factors. RESULTS: This is the first study on the incidence of DI in elderly women. A total of 864 elderly women were interviewed in 2006. The prevalence rate of DI was 4.9%. The incidence rate of DI in the period between 2006 and 2010 was 13.8/1,000 person-years. Associated factors were the presence of chronic obstructive pulmonary disease, hypertension, difficulty with basic activities of daily living (BADL) and instrumental activities of daily living (IADL), polypharmacy and falls in the last year. Poisson's regression analysis showed that falls in the last year and difficulty with at least three IADL were risk factors for DI. CONCLUSIONS: The incidence of DI seems to be high in this population. Falls in the last year and difficulty with at least three IADL were identified as risk factors. Preventive measures must be implemented with public health policies to prevent increases in DI.

IHH Gene Mutations Causing Short Stature With Nonspecific Skeletal Abnormalities and Response to Growth Hormone Therapy.

Context: Genetic evaluation has been recognized as an important tool to elucidate the causes of growth disorders. Objective: To investigate the cause of short stature and to determine the phenotype of patients with IHH mutations, including the response to recombinant human growth hormone (rhGH) therapy. Patients and Methods: We studied 17 families with autosomal-dominant short stature by using whole exome sequencing and screened IHH defects in 290 patients with growth disorders. Molecular analyses were performed to evaluate the potential impact of N-terminal IHH variants. Results: We identified 10 pathogenic or possibly pathogenic variants in IHH, an important regulator of endochondral ossification. Molecular analyses revealed a smaller potential energy of mutated IHH molecules. The allele frequency of rare, predicted to be deleterious IHH variants found in short-stature samples (1.6%) was higher than that observed in two control cohorts (0.017% and 0.08%; P < 0.001). Identified IHH variants segregate with short stature in a dominant inheritance pattern. Affected individuals typically manifest mild disproportional short stature with a frequent finding of shortening of the middle phalanx of the fifth finger. None of them have classic features of brachydactyly type A1, which was previously associated with IHH mutations. Five patients heterozygous for IHH variants had a good response to rhGH therapy. The mean change in height standard deviation score in 1 year was 0.6. Conclusion: Our study demonstrated the association of pathogenic variants in IHH with short stature with nonspecific skeletal abnormalities and established a frequent cause of growth disorder, with a preliminary good response to rhGH.

Aging and decreased glomerular filtration rate: An elderly population-based study.

BACKGROUND: Although a reduced glomerular filtration rate (GFR) in old people has been attributed to physiologic aging, it may be associated with kidney disease or superimposed comorbidities. This study aims to assess the prevalence of decreased GFR in a geriatric population in a developing country and its prevalence in the absence of simultaneous diseases. STUDY DESIGN AND METHODS: This is a cross-sectional study of data from the Saúde, Bem-Estar e Envelhecimento cohort study (SABE study[Health, Well-Being and Aging]), a multiple cohorts study. A multistage cluster sample composed of 1,253 individuals representative of 1,249,388 inhabitants of São Paulo city aged ≥60 years in 2010 was analyzed. The participants answered a survey on socio-demographic factors and health, had blood pressure measured and urine and blood samples collected. GFR was estimated and defined as decreased when <60 mL/min/1.73m2. Kidney damage was defined as dipstick-positive hematuria or urinary protein:creatinine > 0.20 g/g. RESULTS: The prevalence of GFR <60 mL/min/1.73m2 was 19.3%. Individuals with GFR <60 mL/min/1.73m2 were older (75±1 versus 69±1 years, p<0.001), had lower schooling (18 versus 30% with complete 8-year basic cycle, p = 0.010), and higher prevalence of hypertension (82 versus 63%, p<0.001), diabetes (34 versus 26%, p = 0.021), cardiovascular disease (43 versus 24%, p<0.001) and kidney damage (35% versus 15%, p<0.001). Only 0.7% of the entire studied population had GFR <60 mL/min/1.73m2 without simultaneous diseases or kidney damage. Among the individuals with GFR <60 mL/min/1.73m2, 3.5% had neither renal damage nor associated comorbidities, whereas among those with GFR ≥60 mL/min/1.73m2, 11.0% had none of these conditions. Logistic regression showed that older age, cardiovascular disease and hypertension were associated with GFR<60 mL/min/1.73m2. CONCLUSIONS: Decreased GFR was highly prevalent among the geriatric population in a megalopolis of a developing country. It was rarely present without simultaneous chronic comorbidities or kidney damage.

Exomic variants of an elderly cohort of Brazilians in the ABraOM database.

Brazilians are highly admixed with ancestry from Europe, Africa, America, and Asia and yet still underrepresented in genomic databanks. We hereby present a collection of exomic variants from 609 elderly Brazilians in a census-based cohort (SABE609) with comprehensive phenotyping. Variants were deposited in ABraOM (Online Archive of Brazilian Mutations), a Web-based public database. Population representative phenotype and genotype repositories are essential for variant interpretation through allele frequency filtering; since elderly individuals are less likely to harbor pathogenic mutations for early- and adult-onset diseases, such variant databases are of great interest. Among the over 2.3 million variants from the present cohort, 1,282,008 were high-confidence calls. Importantly, 207,621 variants were absent from major public databases. We found 9,791 potential loss-of-function variants with about 300 mutations per individual. Pathogenic variants on clinically relevant genes (ACMG) were observed in 1.15% of the individuals and were correlated with clinical phenotype. We conducted incidence estimation for prevalent recessive disorders based upon heterozygous frequency and concluded that it relies on appropriate pathogenicity assertion. These observations illustrate the relevance of collecting demographic data from diverse, poorly characterized populations. Census-based datasets of aged individuals with comprehensive phenotyping are an invaluable resource toward the improved understanding of variant pathogenicity.

Comprehensive assessment of the disputed RET Y791F variant shows no association with medullary thyroid carcinoma susceptibility.

Accurate interpretation of germline mutations of the rearranged during transfection (RET) proto-oncogene is vital for the proper recommendation of preventive thyroidectomy in medullary thyroid carcinoma (MTC)-prone carriers. To gain information regarding the most disputed variant of RET, ATA-A Y791F, we sequenced blood DNA samples from a cohort of 2904 cancer-free elderly individuals (1261 via Sanger sequencing and 1643 via whole-exome/genome sequencing). We also accessed the exome sequences of an additional 8069 individuals from non-cancer-related laboratories and public databanks as well as genetic results from the Catalogue of Somatic Mutations in Cancer (COSMIC) project. The mean allelic frequency observed in the controls was 0.0031, with higher occurrences in Central European populations (0.006/0.008). The prevalence of RET Y791F in the control databases was extremely high compared with the 40 known RET pathogenic mutations (P=0.00003), while no somatic occurrence has been reported in tumours. In this study, we report new, unrelated Brazilian individuals with germline RET Y791F-only: two tumour-free elderly controls; two individuals with sporadic MTC whose Y791F-carrying relatives did not show any evidence of tumours; and a 74-year-old phaeochromocytoma patient without MTC. Furthermore, we showed that the co-occurrence of Y791F with the strong RET C634Y mutation explains the aggressive MTC phenotypes observed in a large affected family that was initially reported as Y791F-only. Our literature review revealed that limited analyses have led to the misclassification of RET Y791F as a probable pathogenic variant and, consequently, to the occurrence of unnecessary thyroidectomies. The current study will have a substantial clinical influence, as it reveals, in a comprehensive manner, that RET Y791F only shows no association with MTC susceptibility.

Past and present: conditions of life during childhood and mortality of older adults.

OBJECTIVE: To analyze whether socioeconomic and health conditions during childhood are associated with mortality during old age. METHODS: Data were extracted from the SABE Study (Saúde, Bem-estar e Envelhecimento - Health, Welfare and Aging), which were performed in 2000 and 2006. The sample consisted of 2004 (1,355 living and 649 dead) older adults. The statistical analysis was performed based on Poisson regression models, taking into account the time variation of risk observed. Older adults' demographic characteristics and life conditions were evaluated, as were the socioeconomic and lifestyle conditions they acquired during their adult life. RESULTS: Only the area of residence during childhood (rural or urban) remained as a factor associated with mortality at advanced ages. However, this association lost significance when the variables acquired during adulthood were added to the model. CONCLUSIONS: Despite the information regarding the conditions during childhood being limited and perhaps not accurately measure the socioeconomic status and health in the first years of life, the findings of this study suggest that improving the environmental conditions of children and creating opportunities during early adulthood may contribute to greater survival rates for those of more advanced years.

Past and present: conditions of life during childhood and mortality of older adults / Passado e presente: condições de vida na infância e mortalidade de idosos

ABSTRACT OBJECTIVE: To analyze whether socioeconomic and health conditions during childhood are associated with mortality during old age. METHODS: Data were extracted from the SABE Study (Saúde, Bem-estar e Envelhecimento - Health, Welfare and Aging), which were performed in 2000 and 2006. The sample consisted of 2004 (1,355 living and 649 dead) older adults. The statistical analysis was performed based on Poisson regression models, taking into account the time variation of risk observed. Older adults' demographic characteristics and life conditions were evaluated, as were the socioeconomic and lifestyle conditions they acquired during their adult life. RESULTS: Only the area of residence during childhood (rural or urban) remained as a factor associated with mortality at advanced ages. However, this association lost significance when the variables acquired during adulthood were added to the model. CONCLUSIONS: Despite the information regarding the conditions during childhood being limited and perhaps not accurately measure the socioeconomic status and health in the first years of life, the findings of this study suggest that improving the environmental conditions of children and creating opportunities during early adulthood may contribute to greater survival rates for those of more advanced years.

RESUMO OBJETIVO: Analisar se as condições socioeconômicas e de saúde na infância estão associadas à mortalidade em idosos. MÉTODOS: Utilizaram-se os dados do Estudo SABE (Saúde, Bem-estar e Envelhecimento) realizado em 2000 e 2006. A amostra foi composta por 2004 idosos, sendo 1.355 idosos sobreviventes e 649 óbitos. Modelos de Regressão de Poisson foram estimados, levando-se em consideração a variação do tempo de risco. Foram avaliadas características demográficas, condições no início da vida do idoso e condições socioeconômicas e de estilo de vida adquiridos na fase adulta. RESULTADOS: Situação de residência (rural ou urbano) quando criança associou-se à mortalidade nas idades avançadas. No entanto, essa variável perdeu significância quando variáveis que representam características adquiridas na fase adulta foram adicionadas ao modelo. CONCLUSÕES: Mesmo que as informações disponíveis sobre condições na infância sejam limitadas e possam não medir com precisão o status socioeconômico e de saúde nos primeiros anos de vida, os achados sugerem que melhorias nas condições ambientais das crianças e a criação de oportunidades no início da vida adulta podem contribuir para maior sobrevivência nas idades mais avançadas.