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Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data1. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Here, using ancestry deconvolution and inference of identity-by-descent segments, we inferred ancestral population sizes across Mesoamerican regions over time, unravelling Indigenous, colonial and postcolonial demographic dynamics2-6. We observed variation in runs of homozygosity among genomic regions with different ancestries reflecting distinct demographic histories and, in turn, different distributions of rare deleterious variants. We conducted genome-wide association studies (GWAS) for 22 complex traits and found that several traits are better predicted using the Mexican Biobank GWAS compared to the UK Biobank GWAS7,8. We identified genetic and environmental factors associating with trait variation, such as the length of the genome in runs of homozygosity as a predictor for body mass index, triglycerides, glucose and height. This study provides insights into the genetic histories of individuals in Mexico and dissects their complex trait architectures, both crucial for making precision and preventive medicine initiatives accessible worldwide.
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Bancos de Espécimes Biológicos , Genética Médica , Genoma Humano , Genômica , Hispânico ou Latino , Humanos , Glicemia/genética , Glicemia/metabolismo , Estatura/genética , Índice de Massa Corporal , Interação Gene-Ambiente , Marcadores Genéticos/genética , Estudo de Associação Genômica Ampla , Hispânico ou Latino/classificação , Hispânico ou Latino/genética , Homozigoto , México , Fenótipo , Triglicerídeos/sangue , Triglicerídeos/genética , Reino Unido , Genoma Humano/genéticaRESUMO
Demographic models of Latin American populations often fail to fully capture their complex evolutionary history, which has been shaped by both recent admixture and deeper-in-time demographic events. To address this gap, we used high-coverage whole-genome data from Indigenous American ancestries in present-day Mexico and existing genomes from across Latin America to infer multiple demographic models that capture the impact of different timescales on genetic diversity. Our approach, which combines analyses of allele frequencies and ancestry tract length distributions, represents a significant improvement over current models in predicting patterns of genetic variation in admixed Latin American populations. We jointly modeled the contribution of European, African, East Asian, and Indigenous American ancestries into present-day Latin American populations. We infer that the ancestors of Indigenous Americans and East Asians diverged â¼30 thousand years ago, and we characterize genetic contributions of recent migrations from East and Southeast Asia to Peru and Mexico. Our inferred demographic histories are consistent across different genomic regions and annotations, suggesting that our inferences are robust to the potential effects of linked selection. In conjunction with published distributions of fitness effects for new nonsynonymous mutations in humans, we show in large-scale simulations that our models recover important features of both neutral and deleterious variation. By providing a more realistic framework for understanding the evolutionary history of Latin American populations, our models can help address the historical under-representation of admixed groups in genomics research and can be a valuable resource for future studies of populations with complex admixture and demographic histories.
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Genética Populacional , Genoma Humano , Humanos , América Latina , Genoma Humano/genética , Demografia , BrancosRESUMO
Tuberculosis (TB) associated with diabetes mellitus (DM) is a growing problem, particularly in low- and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment (TPT) with isoniazid (INH) or rifampicin (RIF) in people with type 2 DM. Participants were assigned six months of INH 300 mg/day plus pyridoxine 75 mg or three months of RIF 600 mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TPT using INH or RIF is not safe enough to be considered a universal indication to patients with type 2 DM and TB infection. These results underline the need to search for alternative TB preventions with better safety profiles for type 2 DM patients.
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INTRODUCTION: Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients, particularly in people living with human immunodeficiency virus (HIV). TMP/SMX use entails different adverse effects, and its association with early neutropenia is minimally documented. This study aimed to identify the risk of early neutropenia associated with TMP/SMX use in adults living with HIV in Mexico. METHODS: A prospective cohort study was conducted in TMP/SMX-naïve adults living with HIV admitted to a third-level hospital between August 2019 and March 2020. Socio-demographic, clinical, and laboratory data were collected. According to patients' diagnostic, if they required treatment or prophylaxis against PCP, medical staff decided to prescribe TMP/SMX, as it is the first-line treatment. The risk of TMP/SMX induced early neutropenia, as well as associated factors were analyzed through a bivariate model and a multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval. RESULTS: 57 patients were enrolled in the study, of whom 40 patients were in the TMP/SMX treatment-group for treatment or prophylaxis of PCP (204.8 person-years of observation, median 26.5 days) and 17 patients were in the non-treatment group because they did not need the drug for treatment or prophylaxis of PCP (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX-treatment group versus non-treatment group was 7.81 and 1.15 cases per 100 person-years, respectively. After adjusting for stage 3 of HIV infection and neutrophil count <1,500 cells/mm3 at hospital admission, the current use of TMP/SMX was not associated with an increase in the incidence rate ratio of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p = 0.352). CONCLUSIONS: The current use of TMP/SMX in Mexican adults living with HIV was not associated with an increase in the incidence rate ratio of early neutropenia.
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Infecções por HIV , Neutropenia , Pneumonia por Pneumocystis , Humanos , Adulto , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Estudos de Coortes , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/epidemiologia , Pneumonia por Pneumocystis/complicações , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Prospectivos , México/epidemiologia , Estudos Retrospectivos , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Neutropenia/complicaçõesRESUMO
OBJECTIVES: To analyse the relationship between the Frailty Index and 10 oral conditions controlling for nutritional status among Mexican community-dwelling older people. BACKGROUND: Studies suggest that the association between frailty and oral conditions are mediated by nutrition. MATERIALS AND METHODS: This cross-sectional analysis includes 487 community-dwelling men and women aged ≥70 years old. Interview and clinical examinations were performed at participants' homes. Objective (number of natural teeth, root remnants, dental condition, utilisation and functionality of removable dental prostheses and periodontitis) and subjective (utilisation of dental services, self-rated oral health, chewing difficulties and xerostomia) oral variables were collected by trained personnel. The Frailty Index was calculated considering 35 deficits. Nutritional status measured with the Mini-Nutritional assessment (MNA), age, sex, education, and marital status were included as covariates. We fitted 11 multivariate generalised linear models (one for each oral condition), assuming gamma distribution for Frailty Index as the outcome. RESULTS: Participants average age was 78.1 years, 52.1% were women. We observed a higher Frailty Index among those rating their oral health as worse than others their age (5.1%), reporting chewing difficulties often (4.9%) and fairly and very often (7.0%), and xerostomia (4.8%). Age, gender and MNA were consistently associated with the Frailty Index. CONCLUSION: Subjective oral conditions are compatible with the Frailty Index after controlling for older people's nutritional status and covariates.
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Fragilidade , Doenças da Boca , Xerostomia , Masculino , Humanos , Feminino , Idoso , Estudos de Coortes , Estudos Transversais , Fragilidade/epidemiologia , Doenças da Boca/epidemiologia , Saúde Bucal , Estado Nutricional , Xerostomia/complicações , Xerostomia/epidemiologia , Avaliação Geriátrica , Idoso FragilizadoRESUMO
Salivary gland neoplasms are a heterogeneous neoplasm group, including mucoepidermoid carcinoma (MECa), adenoid cystic carcinoma (AdCC), and many others. OBJECTIVE: We aimed to identify new critical genes of MECa and AdCC using bioinformatics analysis. METHODS: Gene expression profile of GSE153283 was analyzed by the GEO2R online tool to use the DAVID software for their subsequent enrichment. Protein-protein interactions (PPI) were visualized using String. Cytoscape with MCODE plugin followed by Kaplan-Meier online for overall survival analysis were performed. RESULTS: 97 upregulated genes were identified for MECa and 86 for AdCC. PPI analysis revealed 22 genes for MECa and 63 for AdCC that were validated by Kaplan-Meier that showed FN1 and SPP1 for MECa, and EGF and ERBB2 for AdCC as more significant candidate genes for each neoplasm. CONCLUSION: With bioinformatics methods, we identify upregulated genes in MECa and AdCC. The resulting candidate genes as possible therapeutic targets were FN1, SPP1, EGF, and ERBB2, and all those genes had been tested as a target in other neoplasm kinds but not salivary gland neoplasm. The bioinformatic evidence is a solid strategy to select them for more extensive research with clinical impact.
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OBJECTIVE: To determine the prevalence and factors related to depressive symptoms in older Mexican adults in urban and rural areas. MATERIALS AND METHODS: Cross-sectional study. We examined older adults from a sample taken from the Mexican Health and Aging Study (MHAS-2018). 14 230 older Mexicans were screened for self-reported depressive symptoms. RESULTS: The prevalence of depressive symptoms was 29.8% (33.4% rural vs. 28.9% urban). In the rural and urban population, the probability of a high prevalence of depressive symptoms was higher in older adults with multimorbidity ≥3, severe pain, and fair/poor SRH. Only in the urban population the prevalence of depressive symptoms increased with lower schooling. CONCLUSION: Identification of the factors related to depressive symptoms may help healthcare professionals provide better treatment for specific groups in the population.
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Depressão , População Rural , Idoso , Envelhecimento , Estudos Transversais , Depressão/epidemiologia , Humanos , PrevalênciaRESUMO
Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.
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Measles continues to be one of the leading causes of child mortality worldwide, even though a highly effective vaccine has existed for more than 40 years. We aimed to describe the seroprevalence of measles antibodies in Mexico in 2012 and the risk factors associated with susceptibility. A total of 7,785 serum samples were analyzed from the National Health and Nutrition Survey in Mexico. This national survey is representative of the general population, including noninstitutionalized adult, adolescent, and child populations. Antibody titers were classified into protective (> 120 mIU/mL) or susceptible (≤ 120 mIU/mL) levels. The weighted seroprevalence and susceptibility of the overall population were 99.37% (95% CI 99.07-99.58) and 0.63% (95% CI 0.42-0.93), respectively. Among 1-to-4-year-old children, 2.18% (95% CI 1.36-3.48) were susceptible to measles. Among adolescents and young adults, the prevalence of susceptibility was as follows: those 15-19 years of age had a prevalence of 0.22% (95% CI 0.09-0.57), and those 30-39 years of age had a prevalence of 1.17% (95% CI 0.47-2.85). Susceptibility was associated with young age, living in Mexico City, living in crowded households and unknown or nonvaccinated status among 1- to 5-year-old children. Although the overall sample population seroprevalence for measles is above 95%, increased susceptibility among younger children signals the importance of the timely administration of the first vaccine dose at 12 months of age. Furthermore, increased susceptibility among specific subgroups indicates the need to reinforce current vaccination policies, including the immunization of unvaccinated or incompletely vaccinated individuals from 10 to 39 years of age.
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Anticorpos Antivirais/sangue , Suscetibilidade a Doenças/sangue , Sarampo/imunologia , Sarampo/prevenção & controle , Estudos Soroepidemiológicos , Adolescente , Adulto , Criança , Pré-Escolar , Suscetibilidade a Doenças/imunologia , Feminino , Humanos , Lactente , Masculino , Vacina contra Sarampo/uso terapêutico , México , Análise Multivariada , Testes de Neutralização , Prevalência , Probabilidade , Tamanho da Amostra , Classe Social , Vacinação/estatística & dados numéricos , Adulto JovemRESUMO
Background: We aimed to elucidate household and community-level shedding and transmission of trivalent oral polio vaccine (tOPV) in communities with inactivated polio vaccine (IPV) routine immunization after tOPV is administered during a national health week (NHW). Methods: We conducted a 3-arm, randomized trial with data collected at baseline through 10 weeks post-NHW in households with at least 1 child <5 years old in 3 semi-rural communities in Orizaba, Mexico. Selected communities were geographically isolated but socio-demographically similar. Each community was assigned an oral polio vaccine (OPV) immunization rate: 10, 30, or 70% of participating households. From 2653 households in the 3 communities, ~150 households per community were selected, for 466 in total. Households were randomized as vaccinated or unvaccinated, with only 1 child under 5 in the vaccinated household receiving OPV during the February 2015 NHW. No other community members received OPV during this NHW. Stool samples were collected up to 10 weeks post-vaccination for all members of the 466 study households and were analyzed for the presence of OPV serotypes using a multiplex polymerase chain reaction assay. Results: We will report on the factors associated with, and incidence and duration of, household and community shedding and transmission of OPV. The secondary outcomes will characterize temporal and geospatial OPV serotype shedding patterns. Conclusions: The current global polio eradication plan relies on transitioning away from OPV to IPV. This study contributes to understanding patterns of OPV shedding and transmission dynamics in communities with primary IPV immunity, in order to optimize the reduction of OPV transmission.