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Preeclampsia is a multi-organ complication of pregnancy characterized by sudden hypertension and proteinuria that is among the leading causes of preterm delivery and maternal morbidity and mortality worldwide. The heterogeneity of preeclampsia poses a challenge for understanding its etiology and molecular basis. Intriguingly, risk for the condition increases in high-altitude regions such as the Peruvian Andes. To investigate the genetic basis of preeclampsia in a population living at high altitude, we characterized genome-wide variation in a cohort of preeclamptic and healthy Andean families (n = 883) from Puno, Peru, a city located above 3,800 meters of altitude. Our study collected genomic DNA and medical records from case-control trios and duos in local hospital settings. We generated genotype data for 439,314 SNPs, determined global ancestry patterns, and mapped associations between genetic variants and preeclampsia phenotypes. A transmission disequilibrium test (TDT) revealed variants near genes of biological importance for placental and blood vessel function. The top candidate region was found on chromosome 13 of the fetal genome and contains clotting factor genes PROZ, F7, and F10. These findings provide supporting evidence that common genetic variants within coagulation genes play an important role in preeclampsia. A selection scan revealed a potential adaptive signal around the ADAM12 locus on chromosome 10, implicated in pregnancy disorders. Our discovery of an association in a functional pathway relevant to pregnancy physiology in an understudied population of Native American origin demonstrates the increased power of family-based study design and underscores the importance of conducting genetic research in diverse populations.

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The American continent was the last to be occupied by modern humans, and native populations bear the marks of recent expansions, bottlenecks, natural selection, and population substructure. Here we investigate how this demographic history has shaped genetic variation at the strongly selected HLA loci. In order to disentangle the relative contributions of selection and demography process, we assembled a dataset with genome-wide microsatellites and HLA-A, -B, -C, and -DRB1 typing data for a set of 424 Native American individuals. We find that demographic history explains a sizeable fraction of HLA variation, both within and among populations. A striking feature of HLA variation in the Americas is the existence of alleles which are present in the continent but either absent or very rare elsewhere in the world. We show that this feature is consistent with demographic history (i.e., the combination of changes in population size associated with bottlenecks and subsequent population expansions). However, signatures of selection at HLA loci are still visible, with significant evidence selection at deeper timescales for most loci and populations, as well as population differentiation at HLA loci exceeding that seen at neutral markers.

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OBJECTIVES: This article aims to assess the contribution of genomic ancestry and socioeconomic status to obesity in a sample of admixed Latin Americans. METHODS: The study comprised 6776 adult volunteers from Brazil, Chile, Colombia, Mexico, and Peru. Each volunteer completed a questionnaire about socioeconomic variables. Anthropometric variables such as weight, height, waist, and hip circumference were measured to calculate body indices: body mass index, waist-to-hip ratio and waist-to-height ratio (WHtR). Genetic data were extracted from blood samples, and ancestry was estimated using chip genotypes. Multiple linear regression was used to evaluate the relationship between the indices and ancestry, educational level, and economic well-being. The body indices were dichotomized to obesity indices by using appropriate thresholds. Odds ratios were calculated for each obesity index. RESULTS: The sample showed high percentages of obesity by all measurements. However, indices did not overlap consistently when classifying obesity. WHtR resulted in the highest prevalence of obesity. Overall, women with low education level and men with high economic wellness were more likely to be obese. American ancestry was statistically associated with obesity indices, although to a lesser extent than socioeconomic variables. CONCLUSIONS: The proportion of obesity was heavily dependent on the index and the population. Genomic ancestry has a significant influence on the anthropometric measurements, especially on central adiposity. As a whole, we detected a large interpopulation variation that suggests that better approaches to overweight and obesity phenotypes are needed in order to obtain more precise reference values.

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INTRODUCTION: Pain constitutes a major component of the global burden of diseases. Recent studies suggest a strong genetic contribution to pain susceptibility and severity. Whereas most of the available evidence relies on candidate gene association or linkage studies, research on the genetic basis of pain sensitivity using genome-wide association studies (GWAS) is still in its infancy. This protocol describes a proposed GWAS on genetic contributions to baseline pain sensitivity and nociceptive sensitisation in a sample of unrelated healthy individuals of mixed Latin American ancestry. METHODS AND ANALYSIS: A GWAS on genetic contributions to pain sensitivity in the naïve state and following nociceptive sensitisation will be conducted in unrelated healthy individuals of mixed ancestry. Mechanical and thermal pain sensitivity will be evaluated with a battery of quantitative sensory tests evaluating pain thresholds. In addition, variation in mechanical and thermal sensitisation following topical application of mustard oil to the skin will be evaluated. ETHICS AND DISSEMINATION: This study received ethical approval from the University College London research ethics committee (3352/001) and from the bioethics committee of the Odontology Faculty at the University of Antioquia (CONCEPTO 01-2013). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations at international conferences.

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Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.

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Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuals can be of help to characterize the impact of a genome's heterozygosity on the developmental basis of both fluctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do so, three-dimensional (3D) facial shape attributes were explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual ancestry and heterozygosity was estimated using more than 730,000 genome-wide markers. Multivariate techniques applied to geometric morphometric data were used to evaluate the magnitude and significance of directional and fluctuating asymmetry (FA), as well as correlations and multiple regressions aimed to estimate the relationship between facial FA scores and heterozygosity and a set of covariates. Results indicate that directional and FA are both significant, the former being the strongest expression of asymmetry in this sample. In addition, our analyses suggest that there are some specific patterns of facial asymmetries characterizing the different ancestry groups. Finally, we find that more heterozygous individuals exhibit lower levels of asymmetry. Our results highlight the importance of including ancestry-admixture estimators, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise.

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The understanding of the complex genotype-phenotype architecture of human pigmentation has clear implications for the evolutionary history of humans, as well as for medical and forensic practices. Although dozens of genes have previously been associated with human skin color, knowledge about this trait remains incomplete. In particular, studies focusing on populations outside the European-North American axis are rare, and, until now, admixed populations have seldom been considered. The present study was designed to help fill this gap. Our objective was to evaluate possible associations of 18 single nucleotide polymorphisms (SNPs), located within nine genes, and one pseudogene with the Melanin Index (MI) in two admixed Brazilian populations (Gaucho, N = 352; Baiano, N = 148) with different histories of geographic and ethnic colonization. Of the total sample, four markers were found to be significantly associated with skin color, but only two (SLC24A5 rs1426654, and SLC45A2 rs16891982) were consistently associated with MI in both samples (Gaucho and Baiano). Therefore, only these 2 SNPs should be preliminarily considered to have forensic significance because they consistently showed the association independently of the admixture level of the populations studied. We do not discard that the other two markers (HERC2 rs1129038 and TYR rs1126809) might be also relevant to admixed samples, but additional studies are necessary to confirm the real importance of these markers for skin pigmentation. Finally, our study shows associations of some SNPs with MI in a modern Brazilian admixed sample, with possible applications in forensic genetics. Some classical genetic markers in Euro-North American populations are not associated with MI in our sample. Our results point out the relevance of considering population differences in selecting an appropriate set of SNPs as phenotype predictors in forensic practice.

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Objetivo: Identificar factores asociados al éxito de la investigación en salud mental en América Latina y el Caribe, como base para el fortalecimiento de las capacidades de investigación en la región. Material y métodos: Se envió un cuestionario a 792 investigadores y se recibió respuesta de 216. Los probandos fueron clasificados en base a los montos de financiamiento de sus investigaciones y número de publicaciones, en: [1] investigadores con financiamiento superior a USD 5,000 en el último año y con al menos 2 publicaciones internacionales en los últimos 5 años (n=50), [2] investigadores con menor financiamiento/publicaciones (n=88). Setenta y ocho investigadores fueron excluidos de la clasificación por tener información incompleta en estos parámetros. Resultados: Tanto los investigadores en el grupo 1 (IG1) como aquellos en el grupo 2 (IG2) declararon como filiación principal una institución universitaria (66% y 50%, respectivamente); la segunda filiación fue con institutos de investigación en el caso de los de IG1 (48%), y con hospitales (32%) o el sector privado (30%) para los de IG2. Comparativamente, los miembros de IG1 mostraron mayor participación en la formación de recursos humanos (76 vs 47%), consultorías (58 vs 36%), redes colaborativas (78 vs 51%), edición (86 vs 57%) y revisión científica (80 vs 43%); en cuanto a disponibilidad de recursos para investigación, los de IG1 indicaron tener mayor acceso a recursos de internet (66vs.33%), a revistas especializadas (64 vs 43%); a apoyo en epidemiología/bioestadística (82 vs 67%) y ciencias básicas (80 vs 41%), y un mayor número de estudiantes graduados (84 vs 41%). Los grupos difirieron en su percepción de los retos para lograr una eficiente implementación de la investigación en salud mental: IG1 identificaron la falta de recursos humanos capacitados como el principal reto, mientras que IG2, la falta de cultura de investigación en sus instituciones.

Objective: To identify factors associated to success in Mental Health (MH) research in the Latin America and Caribbean region, in order to use them as a basis for the strengthening of research capacities. Material and methods: A questionnaire was sent to 792 researchers in the region. Respondents (n=216) were classified according to their research success in: Group 1 researchers (G1Rs): funded with more than USD 5,000 in the last year, authors of at least 2 international publications in the past 5 years (n=50). Group 2 researchers (G2Rs): those reporting less funding or publications (n=88). Researchers who showed missing data in either parameter were excluded (n=78). Results: The main affiliation of both G1Rs and G2Rs were universities (66% and 50%, respectively); the second affiliation of G1Rs were research institutes (48%) while G2Rs were affiliated to hospitals (32%) or the private sector (30%). Compared to G2Rs, G1Rs had higher involvement in human resource training (76 vs 47%), consultantions (58 vs 36%), networking with colleagues (78 vs 51%), participation as scientific editors (86 vs 57%) or reviewers (80 vs 43%), more access to paid internet resources (66 vs 33%), specialized journals (64 vs 43%). In terms of research resources, GR1s declared having more support in epidemiology/biostatistics (82 vs 67%) and basic sciences (80 vs 41%); and more graduate students (84 vs 41%). G1Rs and G2Rs also differed in prioritizing the challenges they envisage for implementing mental health research: G1Rs ranked the lack of trained resources as the main challenge, while G2Rs remarked on the lack of research culture in their institutions. Conclusions: Our results identify mental health care institutions as the main focus for strengthening of research capacity . This task could be achieved through an intensive interactive work with already stronger universities and research institutes in the region.

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Objetivo: evaluar el estado de la investigación en ciencias básicas (CB) dentro del ámbito de la salud mental (SM), en países de América Latina y el Caribe (pALC). Material y métodos: Se recopiló información de bases de datos de publicaciones (PubMed/PsycINFO), mediante buscadores de internet y muestreo bola de nieve, para identificar investigadores y otros actores involucrados en la gestión de la salud mental. Los 2555 actores identificados recibieron un cuestionario dirigido a evaluar su capacidad personal/ institucional para realizar investigación en SM. Tanto la base de datos de publicaciones como las respuestas al cuestionario fueron utilizadas para el análisis. Resultados: Se identificó 2397 publicaciones en SM, de las cuales 222 estuvieron vinculadas a las CB. Sólo 9 de los 30 ALC tenían publicaciones en esta área. Uno de cada cuatro investigadores en Sm de la región la mayoría psiquiatras y neurólogos declaró tener entrenamiento formal en Cb. El 41% de los investigadores declaró contar con apoyo técnico para la investigación en CB en sus instituciones. Sólo 10% de los proyectos de investigación realizados en os últimos 5 años estuvieron relacionados a las CB. De estos, un 62% se realizó con colaboración local, y 30% con colaboradores de países desarrollados. La financiación provino principalmente de fundaciones, ONGs y universidades. Las principales motivaciones de los investigadores de SM en el área de las CB fueron el interés personal (77%), y la carga de enfermedad (63%). La investigación en CB no fue considerada una prioridad por la mayor parte de los investigadores (55%) y tomadores de decisión (56%). Los investigadores con entrenamiento formal en CB tuvieron más publicaciones y accedieron a mayores fondos de investigación que el resto de investigadores. Conclusiones: La investigación en CB en el área de SM permanece relegada en la región.

Objective: To evaluate the status of basic science (BSci) research in mental health (MH) in Latin American and the Caribbean (LAC) countries. Material and methods: A questionnaire was sent to 2555 MH researchers and stakeholders identified by a mapping process through publication databases (PubMed/PsycINFO), internet searches of institutions, and snowball sampling. The Questionnaire was designed to obtain information about their capacity for MH research. Both, the publication database and the questionnaire responses were the basis for all analyses. Results: Two hundred twenty-two out of 2397 MH publications were related to BSci. Only 9 LAC countries had MH publications in this area. One out of four researchers in MH in the region most of them psychiatrists and neurologists had formal training in BSci research methods. Forty one percent of them declared to have technical support for BSci research from their institutions. Barely 10% of the research projects in the past 5 year had a BSci approach. From them, 62% were local projects, and% were done in collaborations with developed countries, being funded mainly by NGOs or foundations. The main motivations for research in BSci were personal interest (77%) and burden of disease (63%). BSci research was not considered a priority by most researchers (55%) or stakeholders (56%). BSci researchers published more and had better financing than non-BSci is an integral component of MH research and cannot de set aside when establishing agendas and setting priorities in this health area. Given their characteristics, BSci researchers could effectively contribute to improve MH research capacity in the region.

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OBJECTIVE: The World Health Organization Atlas Project identified important deficiencies in world mental and neurological health resources. These deficiencies, especially evident in low and middle-income countries, can be overcome by improving research capacity. The objective of this study is to assess the status of mental and neurological research in Latin American countries and identify the main difficulties encountered in conducting research, publishing results, and shaping health policies, interventions, and programs. METHOD: Semi-structured interviews were conducted with 34 key informants from 13 Latin American countries. RESULTS: Participants reported that production of mental and neurological research in Latin American countries is low. Lack of financial and human resources, including lack of support from government agencies, were identified as the main factors contributing to the dearth of local research. The few research projects that do take place in Latin American countries are often funded at researchers' personal expense. Few policies, interventions, or programs are generated from research results. To address these deficiencies, participants called for training in research methodology, mechanisms for identifying funding opportunities, and greater recognition of their research products. CONCLUSIONS: Researchers and stakeholders recognize the need to mobilize local and international efforts aimed at strengthening research capacity and results implementation. This will lead to an overall optimization of mental and neurological research in the region.

OBJETIVO: El proyecto Atlas de la Organización Mundial de la Salud identifica importantes deficiencias en salud mental y neurológica. Estas deficiencias, especialmente evidentes en países de medianos y bajos ingresos, pueden resolverse mejorando las capacidades en investigación. El objetivo de este estudio es evaluar el estado de la investigación en salud mental y neurológica en países Latinoamericanos, e identificar las principales dificultades encontradas al hacer investigación, publicar resultados, y generar políticas, intervenciones, y programas. MÉTODO: Entrevistas semi-estructuradas fueron realizadas a 34 informantes de 13 países Latinoamericanos. RESULTADOS: La producción de investigación en salud mental y neurológica en países Latinoamericanos es escasa, debido principalmente a la carencia de recursos financieros y humanos, incluyendo el casi ausente apoyo de agencias gubernamentales. Los pocos proyectos de investigación que se llevan a cabo son financiados mayormente con recursos propios de los investigadores. Pocas políticas, intervenciones o programas son generados a partir de resultados de investigación. Resolver estas deficiencias requerirá entrenar profesionales en metodología de la investigación, identificar oportunidades de financiación y lograr un mayor reconocimiento de los productos de la investigación. CONCLUSIONES: Hay necesidad de movilizar esfuerzos locales e internacionales orientados a fortalecer las capacidades en investigación y la implementación de resultados. Esto llevará a una optimización general de la investigación.

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OBJECTIVE: The World Health Organization Atlas Project identified important deficiencies in world mental and neurological health resources. These deficiencies, especially evident in low and middle-income countries, can be overcome by improving research capacity. The objective of this study is to assess the status of mental and neurological research in Latin American countries and identify the main difficulties encountered in conducting research, publishing results, and shaping health policies, interventions, and programs. METHOD: Semi-structured interviews were conducted with 34 key informants from 13 Latin American countries. RESULTS: Participants reported that production of mental and neurological research in Latin American countries is low. Lack of financial and human resources, including lack of support from government agencies, were identified as the main factors contributing to the dearth of local research. The few research projects that do take place in Latin American countries are often funded at researchers' personal expense. Few policies, interventions, or programs are generated from research results. To address these deficiencies, participants called for training in research methodology, mechanisms for identifying funding opportunities, and greater recognition of their research products. CONCLUSIONS: Researchers and stakeholders recognize the need to mobilize local and international efforts aimed at strengthening research capacity and results implementation. This will lead to an overall optimization of mental and neurological research in the region.

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Se presenta el estudio de la tasa de transporte de Litio (TTLi) en cinco grupos de personas: Control, pacientes con Enfermedad maníaco-depresiva (EMD), pacientes de Hipertensión Arterial Esencial (HAE) y parientes de EMD y HAE. Se estudia también la TTLi en 13 familias de EMD (dos a tres generaciones). Los resultados obtenidos nos llevan a la conclusión que la trasmisión genética de la EMD, en los casos en que el cromosoma X es el comprometido, es de carácter recesivo, mientras que en la HAE es de carácter dominante, y sugerimos que el estudio de la TTLi podría ser un elemento valioso para el diagnóstico del rasgo genético de la presencia potencial de ambas enfermedades, dentro de las limitaciones que son discutidas en la sección pertinente

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