RESUMEN
Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.
Asunto(s)
Colecistectomía , Neoplasias de la Vesícula Biliar , Análisis de Series de Tiempo Interrumpido , Humanos , Chile/epidemiología , Colecistectomía/estadística & datos numéricos , Colecistectomía/métodos , Femenino , Persona de Mediana Edad , Masculino , Adulto , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias del Sistema Digestivo/cirugía , Neoplasias del Sistema Digestivo/mortalidad , Anciano , Análisis de DatosRESUMEN
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.
Asunto(s)
Preeclampsia , Altitud , Factores de Coagulación Sanguínea , Proteínas Sanguíneas/genética , Estudios de Casos y Controles , Factor VII/genética , Factor X/genética , Femenino , Humanos , Perú/epidemiología , Placenta , Preeclampsia/epidemiología , Preeclampsia/genética , EmbarazoRESUMEN
Self-perception of ethnicity is a complex social trait shaped by both, biological and non-biological factors. We developed a comprehensive analysis of ethnic self-perception (ESP) on a large sample of Latin American mestizos from five countries, differing in age, socio-economic and education context, external phenotypic attributes and genetic background. We measured the correlation of ESP against genomic ancestry, and the influence of physical appearance, socio-economic context, and education on the distortion observed between both. Here we show that genomic ancestry is correlated to aspects of physical appearance, which in turn affect the individual ethnic self-perceived ancestry. Also, we observe that, besides the significant correlation among genomic ancestry and ESP, specific physical or socio-economic attributes have a strong impact on self-perception. In addition, the distortion among ESP and genomic ancestry differs across age ranks/countries, probably suggesting the underlying effect of past public policies regarding identity. Our results indicate that individuals' own ideas about its origins should be taken with caution, especially in aspects of modern life, including access to work, social policies, and public health key decisions such as drug administration, therapy design, and clinical trials, among others.
Asunto(s)
Etnicidad/genética , Etnicidad/psicología , Autoimagen , Adulto , Anciano , Escolaridad , Femenino , Antecedentes Genéticos , Humanos , América Latina/etnología , Masculino , Persona de Mediana Edad , Fenotipo , Factores SocioeconómicosRESUMEN
The feathers of tropical birds were one of the most significant symbols of economic, social, and sacred status in the pre-Columbian Americas. In the Andes, finely produced clothing and textiles containing multicolored feathers of tropical parrots materialized power, prestige, and distinction and were particularly prized by political and religious elites. Here we report 27 complete or partial remains of macaws and amazon parrots from five archaeological sites in the Atacama Desert of northern Chile to improve our understanding of their taxonomic identity, chronology, cultural context, and mechanisms of acquisition. We conducted a multiproxy archaeometric study that included zooarchaeological analysis, isotopic dietary reconstruction, accelerated mass spectrometry radiocarbon dating, and paleogenomic analysis. The results reveal that during the Late Intermediate Period (1100 to 1450 CE), Atacama oasis communities acquired scarlet macaws (Ara macao) and at least five additional translocated parrot species through vast exchange networks that extended more than 500 km toward the eastern Amazonian tropics. Carbon and nitrogen stable isotopes indicate that Atacama aviculturalists sustained these birds on diets rich in marine bird guano-fertilized maize-based foods. The captive rearing of these colorful, exotic, and charismatic birds served to unambiguously signal relational wealth in a context of emergent intercommunity competition.
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Amazona/fisiología , Fósiles/anatomía & histología , Mascotas/fisiología , Amazona/clasificación , Animales , Chile , Dieta , Plumas/anatomía & histología , Mascotas/clasificación , FilogeografíaRESUMEN
BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10-5 ) and Europeans (P = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.
Asunto(s)
Índice de Masa Corporal , Proteína C-Reactiva/análisis , Neoplasias de la Vesícula Biliar/etiología , Cálculos Biliares/complicaciones , Adulto , Factores de Edad , Chile/epidemiología , Europa (Continente)/epidemiología , Femenino , Neoplasias de la Vesícula Biliar/epidemiología , Neoplasias de la Vesícula Biliar/genética , Cálculos Biliares/epidemiología , Predisposición Genética a la Enfermedad/genética , Variación Genética , Humanos , Masculino , Análisis de la Aleatorización Mendeliana , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
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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Indio Americano o Nativo de Alaska/genética , Demografía , Sitios Genéticos , Antígenos HLA/genética , Selección Genética , Alelos , Variación Genética , Geografía , Haplotipos/genética , Heterocigoto , Homocigoto , Humanos , Repeticiones de Microsatélite/genética , América del Norte , Tamaño de la Muestra , América del SurRESUMEN
Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10-6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10-10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.
Asunto(s)
Indio Americano o Nativo de Alaska/genética , Acuaporina 4/genética , Predisposición Genética a la Enfermedad , Antígenos HLA/genética , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/genética , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Humanos , Masculino , México/epidemiologíaRESUMEN
BACKGROUND: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence. METHODS: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication. RESULTS: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low. CONCLUSION: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.
Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Neoplasias de la Vesícula Biliar/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Chile/epidemiología , Europa (Continente)/epidemiología , Femenino , Neoplasias de la Vesícula Biliar/epidemiología , Estudios de Asociación Genética , Humanos , Indígenas Sudamericanos/genética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Población Blanca/genéticaRESUMEN
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.
Asunto(s)
Obesidad/epidemiología , Obesidad/genética , Factores Socioeconómicos , Adulto , Brasil/epidemiología , Chile/epidemiología , Colombia/epidemiología , Femenino , Humanos , América Latina/epidemiología , Masculino , México/epidemiología , Persona de Mediana Edad , Obesidad/etnología , Perú/epidemiología , Prevalencia , Clase Social , Adulto JovenRESUMEN
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.
Asunto(s)
Estudio de Asociación del Genoma Completo/métodos , Umbral del Dolor , Dolor/genética , Colombia , Voluntarios Sanos , Humanos , Nociceptores/fisiologíaRESUMEN
BACKGROUND: Serum uric acid (SUA) is a heritable trait associated with cardiovascular risk factors and coronary artery disease (CAD). Genome wide association studies (GWAS) have identified several genes associated with SUA, mainly in European populations. However, to date there are few GWAS in Latino populations, and the role of SUA-associated single nucleotide polymorphisms (SNPs) in cardiovascular disease has not been studied in the Mexican population. METHODS: We performed genome-wide SUA association study in 2153 Mexican children and adults, evaluated whether genetic effects were modified by sex and obesity, and used a Mendelian randomization approach in an independent cohort to study the role of SUA modifying genetic variants in premature CAD. RESULTS: Only two loci were associated with SUA levels: SLC2A9 (ßâ¯=â¯-0.47â¯mg/dl, Pâ¯=â¯1.57â¯×â¯10-42 for lead SNP rs7678287) and ABCG2 (ßâ¯=â¯0.23â¯mg/dl, Pâ¯=â¯2.42â¯×â¯10-10 for lead SNP rs2231142). No significant interaction between SLC2A9 rs7678287 and ABCG2 rs2231142 genotypes and obesity was observed. However, a significant ABCG2 rs2231142 genotype*sex interaction (Pâ¯=â¯0.001) was observed in adults but not in children. Although SUA levels were associated with premature CAD, metabolic syndrome and decreased glomerular filtration rate (eGFR), only ABCG2 rs2231142 was associated with decreased eGFR in the premature CAD group. CONCLUSIONS: SUA elevation was independently associated with premature CAD, metabolic syndrome and decreased eGFR in the Mexican population. However, a Mendelian randomization approach using the lead SUA-associated SNPs (SLC2A9 and ABCG2) did not support a causal role of elevated SUA levels for premature CAD.
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Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple/genética , Ácido Úrico/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Niño , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Humanos , Masculino , Análisis de la Aleatorización Mendeliana/métodos , México/epidemiología , Persona de Mediana Edad , Adulto JovenRESUMEN
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.
Asunto(s)
Migración Humana , Indígenas Norteamericanos/genética , Indígenas Sudamericanos/genética , Haplotipos , Humanos , México , Nariz/anatomía & histología , América del SurRESUMEN
Facial asymmetries are usually measured and interpreted as proxies to developmental noise. However, analyses focused on its developmental and genetic architecture are scarce. To advance on this topic, studies based on a comprehensive and simultaneous analysis of modularity, morphological integration and facial asymmetries including both phenotypic and genomic information are needed. Here we explore several modularity hypotheses on a sample of Latin American mestizos, in order to test if modularity and integration patterns differ across several genomic ancestry backgrounds. To do so, 4104 individuals were analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks placed on each individual. We found a pattern of modularity and integration that is conserved across sub-samples differing in their genomic ancestry background. Specifically, a signal of modularity based on functional demands and organization of the face is regularly observed across the whole sample. Our results shed more light on previous evidence obtained from Genome Wide Association Studies performed on the same samples, indicating the action of different genomic regions contributing to the expression of the nose and mouth facial phenotypes. Our results also indicate that large samples including phenotypic and genomic metadata enable a better understanding of the developmental and genetic architecture of craniofacial phenotypes.
Asunto(s)
Cara/anatomía & histología , Cara/fisiología , Desarrollo Maxilofacial/genética , Adolescente , Adulto , Femenino , Estudio de Asociación del Genoma Completo/métodos , Humanos , América Latina , Masculino , Persona de Mediana Edad , Fenotipo , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study was to examine South American population structure and prehistoric population displacements prior to the Spanish conquest, utilizing mitochondrial DNA haplogroups of extant mixed populations from Mexico, Costa Rica, Venezuela, Colombia, Ecuador, Peru, Bolivia, Brazil, Argentina, and Chile. METHOD: Relative frequencies of four pan-American haplogroups, obtained from published databases, were analyzed to evaluate patterns of variations, population structure and possible prehistoric migration pathways. RESULTS: Patterns of mtDNA variation verify biogeographic drift processes and possible migratory pathways. CONCLUSIONS: We propose an updated model of South American colonization that is fully compatible with previous studies based on autosomal, mtDNA, and Y chromosome variation and with archaeologically-derived culture history.
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ADN Mitocondrial/genética , Variación Genética , Haplotipos , Migración Humana , Arqueología , Costa Rica , Humanos , México , Modelos Genéticos , América del SurRESUMEN
This review aims to summarize information about the genetic etiology of attention deficit disorder with hyperactivity (ADHD), with particular reference to the contributions of our research group. We also discuss the genetic comorbidity estimated from genome-wide single nucleotide polymorphisms (SNP´s) between ADHD and major psychiatric disorders such as schizophrenia (E), major depressive disorder (MDD), bipolar disorder (BD) and autism spectrum disorders (ASD). A high genetic comorbidity was found between E and BD (46%), a moderate comorbidity between MDD and E, MDD and BD and MDD and ADHD (18%, 22% and 10% respectively) and a low comorbidity between E and ASD (2.5%). Furthermore, we show evidence concerning the genetic determination of psychiatric diseases, which is significantly lower when it is estimated from genome-wide SNP´s rather than using traditional quantitative genetic methodology (ADHD = E = 23%, BD = 25%, MDD = 21% and ASD = 17%). From an evolutionary perspective, we suggest that behavioral traits such as hyperactivity, inattention and impulsivity, which play a role in ADHD and perhaps also other hereditary traits which are part of major psychiatric disorders, could have had a high adaptive value during the early stages of the evolution of Homo sapiens. However, they became progressively less adaptive and definitively disadvantageous, to the extreme that they are involved in frequently diagnosed major psychiatric disorders.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Predisposición Genética a la Enfermedad/genética , Carácter Cuantitativo Heredable , Trastorno del Espectro Autista/genética , Trastorno Bipolar/genética , Comorbilidad , Trastorno Depresivo Mayor/genética , Humanos , Esquizofrenia/genéticaRESUMEN
Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1-4.3%, P = 6×10-27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.
Asunto(s)
Neoplasias de la Vesícula Biliar/genética , Estudio de Asociación del Genoma Completo , Indígenas Norteamericanos/genética , Adolescente , Adulto , Chile , Femenino , Neoplasias de la Vesícula Biliar/mortalidad , Genética de Población , Genoma Humano , Genotipo , Humanos , América Latina/epidemiología , Masculino , Factores de RiesgoRESUMEN
This review aims to summarize information about the genetic etiology of attention deficit disorder with hyperactivity (ADHD), with particular reference to the contributions of our research group. We also discuss the genetic comorbidity estimated from genome-wide single nucleotide polymorphisms (SNP´s) between ADHD and major psychiatric disorders such as schizophrenia (E), major depressive disorder (MDD), bipolar disorder (BD) and autism spectrum disorders (ASD). A high genetic comorbidity was found between E and BD (46%), a moderate comorbidity between MDD and E, MDD and BD and MDD and ADHD (18%, 22% and 10% respectively) and a low comorbidity between E and ASD (2.5%). Furthermore, we show evidence concerning the genetic determination of psychiatric diseases, which is significantly lower when it is estimated from genome-wide SNP´s rather than using traditional quantitative genetic methodology (ADHD = E = 23%, BD = 25%, MDD = 21% and ASD = 17%). From an evolutionary perspective, we suggest that behavioral traits such as hyperactivity, inattention and impulsivity, which play a role in ADHD and perhaps also other hereditary traits which are part of major psychiatric disorders, could have had a high adaptive value during the early stages of the evolution of Homo sapiens. However, they became progressively less adaptive and definitively disadvantageous, to the extreme that they are involved in frequently diagnosed major psychiatric disorders.
Asunto(s)
Humanos , Trastorno por Déficit de Atención con Hiperactividad/genética , Carácter Cuantitativo Heredable , Predisposición Genética a la Enfermedad/genética , Esquizofrenia/genética , Trastorno Bipolar/genética , Comorbilidad , Trastorno Depresivo Mayor/genética , Trastorno del Espectro Autista/genéticaRESUMEN
The expression of facial asymmetries has been recurrently related with poverty and/or disadvantaged socioeconomic status. Departing from the developmental instability theory, previous approaches attempted to test the statistical relationship between the stress experienced by individuals grown in poor conditions and an increase in facial and corporal asymmetry. Here we aim to further evaluate such hypothesis on a large sample of admixed Latin Americans individuals by exploring if low socioeconomic status individuals tend to exhibit greater facial fluctuating asymmetry values. To do so, we implement Procrustes analysis of variance and Hierarchical Linear Modelling (HLM) to estimate potential associations between facial fluctuating asymmetry values and socioeconomic status. We report significant relationships between facial fluctuating asymmetry values and age, sex, and genetic ancestry, while socioeconomic status failed to exhibit any strong statistical relationship with facial asymmetry. These results are persistent after the effect of heterozygosity (a proxy for genetic ancestry) is controlled in the model. Our results indicate that, at least on the studied sample, there is no relationship between socioeconomic stress (as intended as low socioeconomic status) and facial asymmetries.
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Asimetría Facial/epidemiología , Asimetría Facial/genética , Adolescente , Adulto , Femenino , Heterocigoto , Hispánicos o Latinos/genética , Humanos , Masculino , Persona de Mediana Edad , Clase Social , Adulto JovenRESUMEN
BACKGROUND: Amerindian admixture is an important parameter to consider in epidemiological studies in American countries, to make a proper selection of cases and controls. AIM: To compare Amerindian admixture estimates obtained using ABO*A and ABO*O blood group alleles and ancestral identity markers (AIMs) in the mixed Chilean population. SUBJECTS AND METHODS: Amerindian admixture rates were determined in 720 Chilean volunteers residing in Arica and born in the 15 regions of the country, using ABO*O and ABO*A alleles and 40 AIMs selected from more than 500,000 single nucleotide polymorphisms (SNPs). RESULTS: Mean admixture estimates obtained using ABO*O and ABO*A alleles and AIMs were 35, 47% and 48% respectively. There was concordance in estimates, with the exception of the admixture based on ABO*O allele and AIMs. CONCLUSIONS: In Chile, Amerindian admixture estimates obtained using ABO*A could be used as an alternative to AIMs in justified cases provided the sample size is reasonably large.
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Sistema del Grupo Sanguíneo ABO/genética , Indígenas Sudamericanos/genética , Población Blanca/genética , Chile/etnología , Femenino , Frecuencia de los Genes/genética , Marcadores Genéticos/genética , Genética de Población , Humanos , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Reproducibilidad de los ResultadosRESUMEN
Studies performed in the Andean plateau, one of the highest inhabited areas in the world, have reported that reduced availability of oxygen is associated to fetal growth retardation and lower birth weight, which are established predictors of morbidity and mortality during the first year of life. To test this hypothesis, perinatal variables of neonates born at the Juan Noé Hospital of Arica, Chile, were analyzed in relation to altitude of residence and Aymara ancestry of their mothers. The study population comprised the offspring of 5,295 mothers born between February 2004 and August 2010. Information included birth weight, height, head circumference, gestational age, altitude of residence and socioeconomic status, and was obtained from medical records. Mother´s ancestry was assessed based on surnames which were linked to percentages of Aymara admixture estimates relying on 40 selected ancestry informative markers. After correcting for the effect of multicollinearity among predictor variables, neonates born to mothers with an increased component of Aymara ancestry showed significantly higher birth weight and height at sea level, a marginally significant (p-value 0.06) decrease of birth weight and a significant decrease of height with altitude in comparison with the offspring of mothers with low Aymara ancestry. Since observed tendencies are suggestive of a possible genetic adaptation to hypoxia of the Chilean Aymara, we discuss briefly preliminary evidence related to fetal oxygen transport, particularly polymorphisms in the promoters of the HBG1 and HBG2 genes that are modulators of HbF synthesis, obtained in this ethnic group.