X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.

BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Origins, Admixture Dynamics, and Homogenization of the African Gene Pool in the Americas.

The Transatlantic Slave Trade transported more than 9 million Africans to the Americas between the early 16th and the mid-19th centuries. We performed a genome-wide analysis using 6,267 individuals from 25 populations to infer how different African groups contributed to North-, South-American, and Caribbean populations, in the context of geographic and geopolitical factors, and compared genetic data with demographic history records of the Transatlantic Slave Trade. We observed that West-Central Africa and Western Africa-associated ancestry clusters are more prevalent in northern latitudes of the Americas, whereas the South/East Africa-associated ancestry cluster is more prevalent in southern latitudes of the Americas. This pattern results from geographic and geopolitical factors leading to population differentiation. However, there is a substantial decrease in the between-population differentiation of the African gene pool within the Americas, when compared with the regions of origin from Africa, underscoring the importance of historical factors favoring admixture between individuals with different African origins in the New World. This between-population homogenization in the Americas is consistent with the excess of West-Central Africa ancestry (the most prevalent in the Americas) in the United States and Southeast-Brazil, with respect to historical-demography expectations. We also inferred that in most of the Americas, intercontinental admixture intensification occurred between 1750 and 1850, which correlates strongly with the peak of arrivals from Africa. This study contributes with a population genetics perspective to the ongoing social, cultural, and political debate regarding ancestry, admixture, and the mestizaje process in the Americas.

Depressive Symptoms and Self-Rated Health among Brazilian Older Adults: Baseline Data from the Elsi Brazil Study.

OBJECTIVE: This study investigates whether having a higher number of depressive symptoms is associated with negative self-rated health even in the presence of illnesses. METHODS: This is a secondary analysis of the baseline data from the Longitudinal Study of the Health of Elderly Brazilians (ELSI - Brazil), conducted in 2015-2016, using a national sample of 9,412 people aged 50 or over. Self-rated health was dichotomized into "bad or very bad" and "very good or excellent, good or average". Depressive symptoms were assessed through the eight-item Center for Epidemiologic Studies Depression (CES-D8). Sociodemographic variables, information about unhealthy behaviours, and the number of chronic conditions were also analysed. RESULTS: Having depressive symptoms was strongly associated with bad or very bad self-rated health both in the unadjusted and adjusted analyses. There was a reduction in the magnitude of the association when the number of chronic illnesses was included in the multivariate analysis, along with the other sociodemographic variables and unhealthy behaviours (OR 1,35 95% CI 1,31 - 1,39). CONCLUSION: Having depressive symptoms may contribute towards having a poorer perception of health, even in the absence of health conditions. Self-rated health is a multidimensional construct that can accurately reflect a person's state of general mental health.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson Disease.

Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals. We used data from three admixed cohorts: (i) Latin American Research consortium on the GEnetics of Parkinson's Disease (n=1,504) as discover cohort and (ii) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (iii) Bambui Aging cohort (n= 1,442) as replication cohorts. After developing a X-chromosome framework specifically designed for admixed populations, we identified eight linkage disequilibrium regions associated with PD. We fully replicated one of these regions (top variant rs525496; discovery OR [95%CI]: 0.60 [0.478 - 0.77], p = 3.13 × 10 -5 ; replication OR: 0.60 [0.37-0.98], p = 0.04). rs525496 is an expression quantitative trait loci for several genes expressed in brain tissues, including RAB9B, H2BFM, TSMB15B and GLRA4 . We also replicated a previous XWAS finding (rs28602900), showing that this variant is associated with PD in non-European populations. Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies.

Access to, use of and satisfaction with health services among adults enrolled in Brazil's Family Health Strategy: evidence from the 2008 National Household Survey.

OBJECTIVE: To assess the effects of participation in Brazil's primary healthcare programme (the Family Health Strategy or FHS) on access, use and satisfaction with health services among adults. METHODS: Data are from the 2008 National Household Survey (PNAD) on 264 754 adults. This cross-sectional analysis compares FHS enrollees to both non-enrollees and those with private health plans. We calculated predicted probabilities of each outcome stratified by household wealth quintile, rural/urban location and sex using robust Poisson regression. We performed propensity score analysis to assess the differences in access among FHS enrollees and the rest of the population, once relevant socio-demographic characteristics and other determinants of access were balanced. RESULTS: Compared to families with neither FHS enrolment nor private health plans, adult FHS enrollees were generally more likely to have a usual source of care, to have visited a doctor or dentist in the past 12 months, to have access to needed medications and to be satisfied with the care they received. The FHS effect was largest among urban dwellers and the poorest. CONCLUSIONS: The FHS appears to be associated with enhanced access to and utilization of health services in Brazil. However, it has not yet been able to match levels of access experienced by those with private health plans, perhaps because the population served by the FHS is among the poorest, most rural and least healthy in the country.

The influence of primary care and hospital supply on ambulatory care-sensitive hospitalizations among adults in Brazil, 1999-2007.

OBJECTIVES: We assessed the influence of changes in primary care and hospital supply on rates of ambulatory care-sensitive (ACS) hospitalizations among adults in Brazil. METHODS: We aggregated data on nearly 60 million public sector hospitalizations between 1999 and 2007 to Brazil's 558 microregions. We modeled adult ACS hospitalization rates as a function of area-level socioeconomic factors, health services supply, Family Health Program (FHP) availability, and health needs by using dynamic panel estimation techniques to control for endogenous explanatory variables. RESULTS: The ACS hospitalization rates declined by more than 5% annually. When we controlled for other factors, FHP availability was associated with lower ACS hospitalization rates, whereas private or nonprofit hospital beds were associated with higher rates. Areas with highest predicted ACS hospitalization rates were those with the highest private or nonprofit hospital bed supply and with low (< 25%) FHP coverage. The lowest predicted rates were seen for areas with high (> 75%) FHP coverage and very few private or nonprofit hospital beds. CONCLUSIONS: These results highlight the contribution of the FHP to improved health system performance and reflect the complexity of the health reform processes under way in Brazil.

Does undiagnosed diabetes mitigate the association between diabetes and cognitive impairment? Findings from the ELSI-Brazil study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment. However, most of the evidence has been based on self-reported T2DM, and undiagnosed diabetes has not been considered as a separate category. We aimed to examine the extent to which undiagnosed diabetes modifies the association between diabetes and cognitive impairment in a representative sample of Brazilian adults aged 50 years and older. METHODS: We analyzed baseline data from 1944 participants of the Brazilian Longitudinal Study of Aging (ELSI-Brazil) conducted from 2015 to 2016. Diabetes was evaluated based on self-reported doctor diagnosis and glycosylated hemoglobin levels. Participants were classified as diabetics (D), undiagnosed diabetics (UDD), or nondiabetics (ND). Cognitive function was assessed by word list learning and verbal fluency tests. Three multiple logistic regression models were used to evaluate the changes in the strength of the associations. RESULTS: Participants with diabetes had 49% greater odds of exhibiting impaired memory than nondiabetics (odds ratio [OR] = 1.49; 95% CI: 1.01-2.20). By combining UDD and ND, the association between diabetes and impaired memory was attenuated by 2.0%, losing its statistical significance (OR = 1.46; 95% CI: 0.98-2.17). By combining UDD and D, the association was attenuated by 7.4% (OR = 1.38; 95% CI: 1.01-1.90). No significant association was found between T2DM and impaired verbal fluency. CONCLUSION: This study found an association between T2DM and impaired memory but not with impaired verbal fluency. When UDD individuals are considered diabetics, this association is attenuated; when UDD individuals are considered as ND, this association is attenuated to the extent that it loses its statistical significance, affecting thus the clinical interpretation.

Depressive symptoms and self-rated health among Brazilian older adults: baseline data from the ELSI-Brazil study

Objective: To investigate whether having a higher number of depressive symptoms is associated with negative self-rated health (SRH) even in the absence of illness. Methods: This is a secondary analysis of baseline data from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), conducted in 2015-2016, using a national sample of 9,412 people aged 50 or over. SRH was dichotomized into poor or very poor and very good or excellent, good, or average. Depressive symptoms were assessed through the eight-item Center for Epidemiologic Studies Depression Scale (CES-D8). Sociodemographic variables, information about unhealthy behaviors, and the number of chronic conditions were also analyzed. Results: Having depressive symptoms was strongly associated with poor or very poor SRH both in the unadjusted and adjusted analyses. The magnitude of the association was reduced when the number of chronic illnesses was included in the multivariate analysis, along with the other sociodemographic variables and unhealthy behaviors (OR 1.35, 95%CI 1.31-1.39). Conclusion: Having depressive symptoms may contribute towards having a poorer perception of health, even in the absence of health conditions. SRH is a multidimensional construct that can accurately reflect a person's state of general mental health.

The Genomic Impact of European Colonization of the Americas.

The human genetic diversity of the Americas has been affected by several events of gene flow that have continued since the colonial era and the Atlantic slave trade. Moreover, multiple waves of migration followed by local admixture occurred in the last two centuries, the impact of which has been largely unexplored. Here, we compiled a genome-wide dataset of ∼12,000 individuals from twelve American countries and ∼6,000 individuals from worldwide populations and applied haplotype-based methods to investigate how historical movements from outside the New World affected (1) the genetic structure, (2) the admixture profile, (3) the demographic history, and (4) sex-biased gene-flow dynamics of the Americas. We revealed a high degree of complexity underlying the genetic contribution of European and African populations in North and South America, from both geographic and temporal perspectives, identifying previously unreported sources related to Italy, the Middle East, and to specific regions of Africa.

A minimum set of ancestry informative markers for determining admixture proportions in a mixed American population: the Brazilian set.

The Brazilian population is considered to be highly admixed. The main contributing ancestral populations were European and African, with Amerindians contributing to a lesser extent. The aims of this study were to provide a resource for determining and quantifying individual continental ancestry using the smallest number of SNPs possible, thus allowing for a cost- and time-efficient strategy for genomic ancestry determination. We identified and validated a minimum set of 192 ancestry informative markers (AIMs) for the genetic ancestry determination of Brazilian populations. These markers were selected on the basis of their distribution throughout the human genome, and their capacity of being genotyped on widely available commercial platforms. We analyzed genotyping data from 6487 individuals belonging to three Brazilian cohorts. Estimates of individual admixture using this 192 AIM panels were highly correlated with estimates using ~370 000 genome-wide SNPs: 91%, 92%, and 74% of, respectively, African, European, and Native American ancestry components. Besides that, 192 AIMs are well distributed among populations from these ancestral continents, allowing greater freedom in future studies with this panel regarding the choice of reference populations. We also observed that genetic ancestry inferred by AIMs provides similar association results to the one obtained using ancestry inferred by genomic data (370 K SNPs) in a simple regression model with rs1426654, related to skin pigmentation, genotypes as dependent variable. In conclusion, these markers can be used to identify and accurately quantify ancestry of Latin Americans or US Hispanics/Latino individuals, in particular in the context of fine-mapping strategies that require the quantification of continental ancestry in thousands of individuals.