Genetic signatures of gene flow and malaria-driven natural selection in sub-Saharan populations of the "endemic Burkitt Lymphoma belt".

Populations in sub-Saharan Africa have historically been exposed to intense selection from chronic infection with falciparum malaria. Interestingly, populations with the highest malaria intensity can be identified by the increased occurrence of endemic Burkitt Lymphoma (eBL), a pediatric cancer that affects populations with intense malaria exposure, in the so called "eBL belt" in sub-Saharan Africa. However, the effects of intense malaria exposure and sub-Saharan populations' genetic histories remain poorly explored. To determine if historical migrations and intense malaria exposure have shaped the genetic composition of the eBL belt populations, we genotyped ~4.3 million SNPs in 1,708 individuals from Ghana and Northern Uganda, located on opposite sides of eBL belt and with ≥ 7 months/year of intense malaria exposure and published evidence of high incidence of BL. Among 35 Ghanaian tribes, we showed a predominantly West-Central African ancestry and genomic footprints of gene flow from Gambian and East African populations. In Uganda, the North West population showed a predominantly Nilotic ancestry, and the North Central population was a mixture of Nilotic and Southern Bantu ancestry, while the Southwest Ugandan population showed a predominant Southern Bantu ancestry. Our results support the hypothesis of diverse ancestral origins of the Ugandan, Kenyan and Tanzanian Great Lakes African populations, reflecting a confluence of Nilotic, Cushitic and Bantu migrations in the last 3000 years. Natural selection analyses suggest, for the first time, a strong positive selection signal in the ATP2B4 gene (rs10900588) in Northern Ugandan populations. These findings provide important baseline genomic data to facilitate disease association studies, including of eBL, in eBL belt populations.

The Brazilian Longitudinal Study of Aging (ELSI-Brazil): Objectives and Design.

Brazil is experiencing among the world's fastest demographic aging worldwide. This demographic transition is occurring in a context of few resources and great social inequalities. The Brazilian Longitudinal Study of Aging (ELSI-Brazil) is a nationally representative study of 9,412 people aged 50 years or older, residing in 70 municipalities across the 5 Brazilian regions. ELSI-Brazil allows investigations of the aging process, its health, psychosocial and economic determinants, and societal consequences. The baseline examination (2015-2016) included detailed household and individual interviews and physical measurements (blood pressure, anthropometry, grip strength, and timed walk and balance tests). Blood tests and sample storage were performed in a subsample of study participants. Subsequent waves are planned for every 3 years. The study adopts a conceptual framework common to other large-scale longitudinal studies of aging in the world, such as the Health and Retirement Study, allowing cross-national comparisons. The goal of ELSI-Brazil is not only to build an understanding of aging in a large, Western, middle-income country in a rapid demographic transition but also to provide scientific data to support and study policy changes that may affect older adults. We describe the methodology of the study and some descriptive results of the baseline survey.

Origin and dynamics of admixture in Brazilians and its effect on the pattern of deleterious mutations.

While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study.

BACKGROUND: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. METHODS AND FINDINGS: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2-16 assessment waves (median = 3) and a follow-up duration of 2-15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. CONCLUSIONS: Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.

Genetics of Latin American Diversity Project: Insights into population genetics and association studies in admixed groups in the Americas.

Latin Americans are underrepresented in genetic studies, increasing disparities in personalized genomic medicine. Despite available genetic data from thousands of Latin Americans, accessing and navigating the bureaucratic hurdles for consent or access remains challenging. To address this, we introduce the Genetics of Latin American Diversity (GLAD) Project, compiling genome-wide information from 53,738 Latin Americans across 39 studies representing 46 geographical regions. Through GLAD, we identified heterogeneous ancestry composition and recent gene flow across the Americas. Additionally, we developed GLAD-match, a simulated annealing-based algorithm, to match the genetic background of external samples to our database, sharing summary statistics (i.e., allele and haplotype frequencies) without transferring individual-level genotypes. Finally, we demonstrate the potential of GLAD as a critical resource for evaluating statistical genetic software in the presence of admixture. By providing this resource, we promote genomic research in Latin Americans and contribute to the promises of personalized medicine to more people.

Socioeconomic inequalities in health in older adults in Brazil and England.

OBJECTIVES: We examined socioeconomic inequalities in health among older adults in England and Brazil. METHODS: We analyzed nationally representative samples of residents aged 50 years and older in 2008 data from the Brazilian National Household Survey (n = 75,527) and the English Longitudinal Study of Ageing (n = 9589). We estimated prevalence ratios for self-rated health, functional limitations, and reported chronic diseases, by education level and household income tertiles. RESULTS: Brazilians reported worse health than did English respondents. Country-specific differences were higher among the poorest, but also affected the wealthiest persons. We observed a strong inverse gradient of similar magnitude across education and household income levels for most health indicators in each country. Prevalence ratios (lowest vs highest education level) of poor self-rated health were 3.24 in Brazil and 3.50 in England; having 2 or more functional limitations, 1.81 in Brazil and 1.96 in England; and having 1 or more diseases, 1.14 in Brazil and 1.36 in England. CONCLUSIONS: Socioeconomic inequalities in health affect both populations, despite a less pronounced absolute difference in household income and education in Brazil than in England.

Which older Brazilians will accept a COVID-19 vaccine? Cross-sectional evidence from the Brazilian Longitudinal Study of Aging (ELSI-Brazil).

OBJECTIVES: Vaccine hesitancy may represent a barrier to effective COVID-19 immunisation campaigns. This study assesses individual, disease-specific and contextual factors associated with COVID-19 vaccine acceptance among a nationally representative sample of older Brazilian adults. DESIGN: Cross-sectional analysis of data from household interviews and a supplementary telephone survey. SETTING: Brazil and its five geographic regions. PARTICIPANTS: Data are derived from 6584 individuals aged 50 years and over who participated in the second wave of the Brazilian Longitudinal Study of Aging. PRIMARY AND SECONDARY OUTCOME MEASURES: Survey-weighted multinomial logistic regression assesses factors associated with intending, not intending or being uncertain about one's intention to vaccinate against COVID-19. FINDINGS: Seventy-one per cent of study participants intend to receive a COVID-19 vaccine once available, while 17% (representative of nearly 9 million people) have no intention to vaccinate, and 12% are still undecided. Besides age, demographic and health-related factors related to COVID-19 severity and complications were not associated with intention to vaccinate. Those who most trusted social media or friends and family for COVID-19 information and those who did not trust any information source were 68% and 78% more likely to refuse vaccination, respectively, as compared with those who trusted official information sources. People who inconsistently used face masks when outside were 3.4 times more likely than consistent face mask users to intend to refuse vaccination. Higher municipal COVID-19 fatality rates were negatively associated with vaccine refusal. CONCLUSIONS: Most national COVID-19 immunisation strategies identify older individuals as among those prioritised for early vaccination, given their increased risk of more severe symptoms and complications of the disease. Because individual, disease-specific, and contextual factors were associated with vaccine acceptance, there is a clear need for multilevel and multichannel information and outreach campaigns to increase COVID-19 vaccine acceptance among vulnerable older populations.

Tracing the Distribution of European Lactase Persistence Genotypes Along the Americas.

In adulthood, the ability to digest lactose, the main sugar present in milk of mammals, is a phenotype (lactase persistence) observed in historically herder populations, mainly Northern Europeans, Eastern Africans, and Middle Eastern nomads. As the -13910∗T allele in the MCM6 gene is the most well-characterized allele responsible for the lactase persistence phenotype, the -13910C > T (rs4988235) polymorphism is commonly evaluated in lactase persistence studies. Lactase non-persistent adults may develop symptoms of lactose intolerance when consuming dairy products. In the Americas, there is no evidence of the consumption of these products until the arrival of Europeans. However, several American countries' dietary guidelines recommend consuming dairy for adequate human nutrition and health promotion. Considering the extensive use of dairy and the complex ancestry of Pan-American admixed populations, we studied the distribution of -13910C > T lactase persistence genotypes and its flanking haplotypes of European origin in 7,428 individuals from several Pan-American admixed populations. We found that the -13910∗T allele frequency in Pan-American admixed populations is directly correlated with allele frequency of the European sources. Moreover, we did not observe any overrepresentation of European haplotypes in the -13910C > T flanking region, suggesting no selective pressure after admixture in the Americas. Finally, considering the dominant effect of the -13910∗T allele, our results indicate that Pan-American admixed populations are likely to have higher frequency of lactose intolerance, suggesting that general dietary guidelines deserve further evaluation across the continent.

Mild and moderate cognitive impairment and mortality among Brazilian older adults in long-term follow-up: The Bambui Health Aging Study.

OBJECTIVE: To compare mortality in older adults with and without mild or moderate cognitive impairment over 15 years of follow-up in a middle-income country, where little information on this subject is available. METHODS: A total of 1,281 community-dwelling older adults were followed-up for a median of 13.3 years. We evaluated their cognitive impairment using the Mini-Mental State Examination, categorizing it as none (1.0 SD above cutoff means), mild (1.0 SD below cutoff means) or moderate (2.0 SD below cutoff means). The date of death was determined by reviewing death certificates. Cox's proportional hazards models were used to evaluate the risk of mortality in participants with cognitive impairment. RESULTS: Participants with mild or moderate cognitive impairment had a higher mortality risk than those without it in the unadjusted model, but these associations did not remain in the final model. After sex stratification, only men with moderate cognitive impairment had a higher mortality risk in the final model. CONCLUSION: The findings suggest an association between moderate cognitive impairment and all-cause mortality in men in a large Brazilian cohort of older adults.

A population-based study of the association between Trypanosoma cruzi infection and cognitive impairment in old age (the Bambuí Study).

BACKGROUND: Limited clinical data suggest that chronic Trypanosoma cruzi infection, which causes Chagas' disease (ChD), is associated with cognitive impairment. This study investigated this association in a large population-based sample of older adults. METHODS: Participants in this cross-sectional study comprised 1,449 persons aged > or = 60 years from a Brazilian endemic area (Bambuí). Cognitive functioning was ascertained by the Mini-Mental State Examination (MMSE), considering its score in percentiles [< or =14 (<5th percentile), 15-22 (5th to <25th) and > or =23]. Hypothesized risk factors were T. cruzi infection, ChD-related electrocardiographic (ECG) abnormalities and use of digoxin medication. Potential confounders included depressive symptoms, smoking, stroke, hemoglobin, HDL cholesterol, blood glucose, systolic blood pressure, and use of psychoactive medication. RESULTS: The prevalence of T. cruzi infection was 37.6%. There was a graded and independent association between infection and the MMSE score (adjusted odds ratios estimated by ordinal logistic regression = 1.99; 95% CI 1.43-2.76). No significant associations between the MMSE score and ECG abnormalities or digoxin medication use were found. CONCLUSIONS: This study provides for the first time epidemiological evidence of an association between T. cruzi infection and cognitive impairment which was not mediated by either ChD-related ECG abnormalities or digoxin medication use.

Genomic African and Native American Ancestry and 15-Year Cognitive Trajectory: Bambui Study, Brazil.

OBJECTIVES: To investigate the association between African and Native American genomic ancestry and long-term cognitive trajectories in admixed Brazilians. DESIGN: Population-based longitudinal study. SETTING: Bambui-Epigen (Brazil) cohort study. PARTICIPANTS: Adults aged 60 and older (N=1,215) MEASUREMENTS: Participants were followed from January 1997 to December 2011. Cognitive function was assessed annually using the Mini-Mental State Examination (MMSE), totaling 12,208 measurements. We used linear mixed-effects pattern models to assess MMSE score trajectories. Ancestry was assessed using a genome-wide approach. RESULTS: After adjustments for covariates, the highest quintile of African ancestry was associated with poorer baseline cognitive performance (ß=-0.73, 95% confidence interval (CI)=-1.36 to -0.11) but not with cognitive trajectory. Educational level modified the baseline association between highest African ancestry and cognitive performance in that the association was observed only in those with very low (<4 years) education (ß=-1.13, 95% CI=-2.02 to -0.23). No association was found between Native American ancestry and baseline cognitive function or its trajectory. CONCLUSION: Genomic African and Native American ancestry levels had no prognostic value for age-related cognitive decline in this admixed population.

Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America.

The genetic architecture of asthma was relatively well explored. However, some work remains in the field to improve our understanding on asthma genetics, especially in non-Caucasian populations and with regards to commonly neglected genetic variants, such as Copy Number Variations (CNVs). In the present study, we investigated the contribution of CNVs on asthma risk among Latin Americans. CNVs were inferred from SNP genotyping data. Genome wide burden and association analyses were conducted to evaluate the impact of CNVs on asthma outcome. We found no significant difference in the numbers of CNVs between asthmatics and non-asthmatics. Nevertheless, we found that CNVs are larger in patients then in healthy controls and that CNVs from cases intersect significantly more genes and regulatory elements. We also found that a deletion at 6p22.1 is associated with asthma symptoms in children from Salvador (Brazil) and in young adults from Pelotas (Brazil). To support our results, we conducted an in silico functional analysis and found that this deletion spans several regulatory elements, including two promoter elements active in lung cells. In conclusion, we found robust evidence that CNVs could contribute for asthma susceptibility. These results uncover a new perspective on the influence of genetic factors modulating asthma risk.

Genomic African and Native American Ancestry and Chagas Disease: The Bambui (Brazil) Epigen Cohort Study of Aging.

BACKGROUND: The influence of genetic ancestry on Trypanosoma cruzi infection and Chagas disease outcomes is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual proportions of African, European and Native American genomic ancestry with T. cruzi infection and related outcomes in 1,341 participants (aged ≥ 60 years) of the Bambui (Brazil) population-based cohort study of aging. Potential confounding variables included sociodemographic characteristics and an array of health measures. The prevalence of T. cruzi infection was 37.5% and 56.3% of those infected had a major ECG abnormality. Baseline T. cruzi infection was correlated with higher levels of African and Native American ancestry, which in turn were strongly associated with poor socioeconomic circumstances. Cardiomyopathy in infected persons was not significantly associated with African or Native American ancestry levels. Infected persons with a major ECG abnormality were at increased risk of 15-year mortality relative to their counterparts with no such abnormalities (adjusted hazard ratio = 1.80; 95% 1.41, 2.32). African and Native American ancestry levels had no significant effect modifying this association. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that African and Native American ancestry have no influence on the presence of major ECG abnormalities and had no influence on the ability of an ECG abnormality to predict mortality in older people infected with T. cruzi. In contrast, our results revealed a strong and independent association between prevalent T. cruzi infection and higher levels of African and Native American ancestry. Whether this association is a consequence of genetic background or differential exposure to infection remains to be determined.

Socioeconomic Position, But Not African Genomic Ancestry, Is Associated With Blood Pressure in the Bambui-Epigen (Brazil) Cohort Study of Aging.

The study objective is to examine the role of African genome origin on baseline and 11-year blood pressure trajectories in community-based ethnoracially admixed older adults in Brazil. Data come from 1272 participants (aged ≥60 years) of the Bambui cohort study of aging during 11 years of follow-up. Outcome measures were systolic blood pressure, diastolic blood pressure, and hypertension control. Potential confounding variables were demographic characteristics, socioeconomic position (schooling and household income), and health indicators (smoking, sedentary lifestyle, high-density lipoprotein cholesterol, waist circumference, diabetes mellitus, and cardiovascular diseases), including antihypertensive drug use. We used 370 539 single-nucleotide polymorphisms to estimate each individual's African, European, and Native American trihybrid ancestry proportions. Median African, European, and Native American ancestry were 9.6%, 84.0%, and 5.3%, respectively. Among those with African ancestry, 59.4% came from East and 40.6% from West Africa. Baseline systolic and diastolic blood pressure, controlled hypertension, and their respective trajectories, were not significantly (P>0.05) associated with level (in quintiles) of African genomic ancestry. Similar results were found for West and East African subcontinental origins. Lower schooling level (<4 years versus higher) showed a significant and positive association with systolic blood pressure (Adjusted ß=2.92; 95% confidence interval, 0.85-4.99). Lower monthly household income per capita (

Mild and moderate cognitive impairment and mortality among Brazilian older adults in long-term follow-up: The bambui health aging study

Objective: To compare mortality in older adults with and without mild or moderate cognitive impairment over 15 years of follow-up in a middle-income country, where little information on this subject is available. Methods: A total of 1,281 community-dwelling older adults were followed-up for a median of 13.3 years. We evaluated their cognitive impairment using the Mini-Mental State Examination, categorizing it as none (1.0 SD above cutoff means), mild (1.0 SD below cutoff means) or moderate (2.0 SD below cutoff means). The date of death was determined by reviewing death certificates. Cox's proportional hazards models were used to evaluate the risk of mortality in participants with cognitive impairment. Results: Participants with mild or moderate cognitive impairment had a higher mortality risk than those without it in the unadjusted model, but these associations did not remain in the final model. After sex stratification, only men with moderate cognitive impairment had a higher mortality risk in the final model. Conclusion: The findings suggest an association between moderate cognitive impairment and all-cause mortality in men in a large Brazilian cohort of older adults.

Genomic ancestry and ethnoracial self-classification based on 5,871 community-dwelling Brazilians (The Epigen Initiative).

Brazil never had segregation laws defining membership of an ethnoracial group. Thus, the composition of the Brazilian population is mixed, and its ethnoracial classification is complex. Previous studies showed conflicting results on the correlation between genome ancestry and ethnoracial classification in Brazilians. We used 370,539 Single Nucleotide Polymorphisms to quantify this correlation in 5,851 community-dwelling individuals in the South (Pelotas), Southeast (Bambui) and Northeast (Salvador) Brazil. European ancestry was predominant in Pelotas and Bambui (median = 85.3% and 83.8%, respectively). African ancestry was highest in Salvador (median = 50.5%). The strength of the association between the phenotype and median proportion of African ancestry varied largely across populations, with pseudo R(2) values of 0.50 in Pelotas, 0.22 in Bambui and 0.13 in Salvador. The continuous proportion of African genomic ancestry showed a significant S-shape positive association with self-reported Blacks in the three sites, and the reverse trend was found for self reported Whites, with most consistent classifications in the extremes of the high and low proportion of African ancestry. In self-classified Mixed individuals, the predicted probability of having African ancestry was bell-shaped. Our results support the view that ethnoracial self-classification is affected by both genome ancestry and non-biological factors.

Genomic Ancestry, Self-Rated Health and Its Association with Mortality in an Admixed Population: 10 Year Follow-Up of the Bambui-Epigen (Brazil) Cohort Study of Ageing.

BACKGROUND: Self-rated health (SRH) has strong predictive value for mortality in different contexts and cultures, but there is inconsistent evidence on ethnoracial disparities in SRH in Latin America, possibly due to the complexity surrounding ethnoracial self-classification. MATERIALS/METHODS: We used 370,539 Single Nucleotide Polymorphisms (SNPs) to examine the association between individual genomic proportions of African, European and Native American ancestry, and ethnoracial self-classification, with baseline and 10-year SRH trajectories in 1,311 community dwelling older Brazilians. We also examined whether genomic ancestry and ethnoracial self-classification affect the predictive value of SRH for subsequent mortality. RESULTS: European ancestry predominated among participants, followed by African and Native American (median = 84.0%, 9.6% and 5.3%, respectively); the prevalence of Non-White (Mixed and Black) was 39.8%. Persons at higher levels of African and Native American genomic ancestry, and those self-identified as Non-White, were more likely to report poor health than other groups, even after controlling for socioeconomic conditions and an array of self-reported and objective physical health measures. Increased risks for mortality associated with worse SRH trajectories were strong and remarkably similar (hazard ratio ~3) across all genomic ancestry and ethno-racial groups. CONCLUSIONS: Our results demonstrated for the first time that higher levels of African and Native American genomic ancestry--and the inverse for European ancestry--were strongly correlated with worse SRH in a Latin American admixed population. Both genomic ancestry and ethnoracial self-classification did not modify the strong association between baseline SRH or SRH trajectory, and subsequent mortality.

The influence of socioeconomic status on the predictive power of self-rated health for 6-year mortality in English and Brazilian older adults: the ELSA and Bambui cohort studies.

PURPOSE: There is mixed evidence that socioeconomic status (SES) affects the predictive power of self-rated health (SRH) for mortality. We sought to compare the predictive value of SRH for 6-year mortality in English and Brazilian older adults, and to assess whether this association varies by SES in these populations. METHODS: Data came from the English and the Bambui (Brazil) cohort studies of aging. Potential confounding variables included sociodemographic characteristics, lifestyle, self-reported diseases, physical functioning, mental symptoms, and selected biomarker measures. RESULTS: Participants were 5183 English and 1499 Brazilians aged 60 years and over. Low health ratings were independently associated with subsequent mortality in both populations. However, the predictive power of poor SRH for death was much higher for English (a population with higher SES level) than for Brazilians (adjusted hazard ratios 4.45 [95% confidence interval, 3.04-6.51] and 1.88 [1.25-2.81], respectively). In both populations, the predictive value of SRH for mortality was higher among those in the highest income tertile. CONCLUSIONS: Our results suggest that the association between SRH and mortality is underestimated in populations and in subgroups of population with low SES level. Further international research is needed to examine the generalizability of this pattern.