Biology subjects

Horta, B. L.

Publications and source records attributed to Horta, B. L..

7 recordsLinked to original sources

bioRxiv2024

Comparing the effect of imputation reference panel composition in four distinct Latin American cohorts

Genome-wide association studies have been useful in identifying genetic risk factors for various phenotypes. These studies rely on imputation and many existing panels are largely composed of individuals of European ancestry, resulting in lower levels of imputation quality in underrepresented populations. We aim to analyze how the composition of imputation reference panels affects imputation quality in four target Latin American cohorts. We compared imputation quality for chromosomes 7 and X when altering the imputation reference panel by: 1) increasing the number of Latin American individuals; 2) excluding either Latin American, African, or European individuals, or 3) increasing the Indigenous American (IA) admixture proportions of included Latin Americans. We found that increasing the number of Latin Americans in the reference panel improved imputation quality in the four populations; however, there were differences between chromosomes 7 and X in some cohorts. Excluding Latin Americans from analysis resulted in worse imputation quality in every cohort, while differential effects were seen when excluding Europeans and Africans between and within cohorts and between chromosomes 7 and X. Finally, increasing IA-like admixture proportions in the reference panel increased imputation quality at different levels in different populations. The difference in results between populations and chromosomes suggests that existing and future reference panels containing Latin American individuals are likely to perform differently in different Latin American populations.

genomics↗

bioRxiv2020

Whole-genome sequencing of 1,171 elderly admixed individuals from the largest Latin American metropolis (Sao 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 enabled identifying ~2,000 novel mobile element insertions, nearly 5Mb of genomic segments absent from human genome reference, and over 140 novel alleles from HLA genes. We reclassified and curated nearly four hundred variant's pathogenicity assertions in genes associated with dominantly inherited Mendelian disorders and calculated the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observed 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.

genomics↗

bioRxiv2019

The genomic impact of European colonization of the Americas

The human genetic diversity of the Americas has been shaped 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.\n\nHere 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 i) the genetic structure, ii) the admixture profile, iii) the demographic history and iv) sex-biased gene-flow dynamics, of the Americas.\n\nWe 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.

genomics↗

bioRxiv2019

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 genome-wide analysis of 6,267 individuals from 22 populations and observed an enrichment in West-African ancestry in northern latitudes of the Americas, whereas South/East African ancestry is more prevalent in southern South-America. This pattern results from distinct geographic and geopolitical factors leading to population differentiation. However, we observed a decrease of 68% in the African gene pool between-population diversity within the Americas when compared to 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 is consistent with the excess of West-Central Africa ancestry (the most prevalent in the Americas) in the US and Southeast-Brazil, respect to historical-demography expectations. Also, in most of the Americas, admixture intensification occurred between 1,750 and 1,850, 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, race, and admixture in the Americas.\n\nSignificance StatementDifferently from most genetic studies, that have estimated the overall African ancestry in the Americas, we perform a finer geographic analysis and infer how different African groups contributed to North-, South-American and Caribbean populations, in the context of geographic and geopolitical factors. We also perform a formal comparison of information from demographic history records of the Transatlantic Slave Trade with inferences based on genomic diversity of current populations. Our approach reveals the distinct regional African ancestry roots of different populations from North-, South-America and the Caribe and other important aspects of the historical process of mestizaje and its dynamics in the American continent.

genetics↗

bioRxiv2017

Effect modification of FADS2 polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis

BackgroundAccumulating evidence suggests that breastfeeding benefits the childrens intelligence. Long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk may explain part of this association. Under a nutritional adequacy hypothesis, an interaction between breastfeeding and genetic variants associated with endogenous LC-PUFAs synthesis might be expected. However, the literature on this topic is controversial.\n\nMethods and FindingsWe investigated this GenexEnvironment interaction in a de novo meta-analysis involving >12,000 individuals in the primary analysis, and >45,000 individuals in a secondary analysis using relaxed inclusion criteria. Our primary analysis used ever breastfeeding, FADS2 polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores. Using random effects meta-analysis, ever breastfeeding was associated with 0.17 (95% CI: 0.03; 0.32) higher Z scores in IQ, or about 2.1 points. There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e., difference between genetic groups of the difference in IQZ scores comparing ever with never breastfed individuals) of 0.12 (95% CI: -0.19; 0.43) and 0.06 (95% CI: -0.16; 0.27) for the rs174575 and rs1535 variants, respectively. Secondary analyses corroborated these results. In studies with >5.85 and <5.85 months of breastfeeding duration, pooled estimates for the rs174575 variant were 0.50 (95% CI: -0.06; 1.06) and 0.14 (95% CI: -0.10; 0.38), respectively, and 0.27 (95% CI: -0.28; 0.82) and -0.01 (95% CI: -0.19; 0.16) for the rs1535 variant. However, between-group comparisons were underpowered.\n\nConclusionsOur findings do not support an interaction between ever breastfeeding and FADS2 polymorphisms. However, our subgroup analysis raises the possibility that breastfeeding supplies LC-PUFAs requirements for cognitive development (if such threshold exists) if it lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and would improve our understanding on the role of breastfeeding duration in the breastfeedingxFADS2 interaction.

epidemiology↗

bioRxiv2017

Metabolic profiling of adiponectin levels in adults: Mendelian randomization analysis

BackgroundAdiponectin, a circulating adipocyte-derived protein has insulin-sensitizing, anti-inflammatory, anti-atherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown.\n\nObjectivesOur aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile.\n\nMethodsWe applied multivariable regression in up to 5,906 adults and Mendelian randomization (using cis-acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analysing the causal effect of adiponectin in the metabolic profile of up to 38,058 adults. Participants were largely European from six longitudinal studies and one genome-wide association consortium.\n\nResultsIn the multivariable regression analyses, higher circulating adiponectin was associated with higher HDL lipids and lower VLDL lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high risk groups (defined by age and occurrence of previous cardiovascular event) and one study with admixed population.\n\nConclusionOur findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant.

epidemiology↗

bioRxiv2017

Association Between Genetically Elevated Levels Of Inflammatory Biomarkers And Risk Of Schizophrenia: A Two-Sample Mendelian Randomisation Study

BackgroundPositive associations between inflammatory biomarkers and risk of psychiatric disorders, including schizophrenia, have been reported in observational studies. However, conventional observational studies are prone to bias such as reverse causation and residual confounding.\n\nMethodsIn this study, we used summary data to evaluate the association of genetically elevated C reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra) and soluble interleukin-6 receptor (IL-6R) levels with schizophrenia in a two-sample Mendelian randomisation design.\n\nResultsThe pooled odds ratio estimate using 18 CRP genetic instruments was 0.90 (95% CI: 0.84; 0.97) per two-fold increment in CRP levels; consistent results were obtained using different Mendelian randomisation methods and a more conservative set of instruments. The odds ratio for soluble IL-6R was 1.06 (95% CI: 1.01; 1.12) per two-fold increment. Estimates for IL-1Ra were inconsistent among instruments and pooled estimates were imprecise and centred on the null.\n\nConclusionUnder Mendelian randomisation assumptions, our findings suggest a protective causal effect of CRP and a risk-increasing causal effect of soluble IL-6R (potentially mediated at least in part by CRP) on schizophrenia risk.

epidemiology↗