RESUMO
We conducted an exome-wide association study of childhood acute lymphoblastic leukemia (ALL) among Hispanics to confirm and identify novel variants associated with disease risk in this population. We used a case-parent trio study design; unlike more commonly used case-control studies, this study design is ideal for avoiding issues with population stratification bias among this at-risk ethnic group. Using 710 individuals from 323 Guatemalan and US Hispanic families, two inherited SNPs in ARID5B reached genome-wide level significance: rs10821936, RR = 2.31, 95% CI = 1.70-3.14, p = 1.7×10-8 and rs7089424, RR = 2.22, 95% CI = 1.64-3.01, p = 5.2×10-8. Similar results were observed when restricting our analyses to those with the B-ALL subtype: ARID5B rs10821936 RR = 2.22, 95% CI = 1.63-3.02, p = 9.63×10-8 and ARID5B rs7089424 RR = 2.13, 95% CI = 1.57-2.88, p = 2.81×10-7. Notably, effect sizes observed for rs7089424 and rs10821936 in our study were >20% higher than those reported among non-Hispanic white populations in previous genetic association studies. Our results confirmed the role of ARID5B in childhood ALL susceptibility among Hispanics; however, our assessment did not reveal any strong novel inherited genetic risks for acute lymphoblastic leukemia among this ethnic group.
Assuntos
Proteínas de Ligação a DNA/genética , Exoma , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hispânico ou Latino/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Fatores de Transcrição/genética , Adolescente , Alelos , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Genótipo , Guatemala , Humanos , Lactente , Recém-Nascido , Masculino , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , TexasRESUMO
INTRODUCTION: The genetic heritability for sensation-seeking tendencies ranges from 40 to 60%. Sensation-seeking behaviors typically manifest during adolescence and are associated with alcohol and cigarette experimentation in adolescents. Social disinhibition is an aspect of sensation-seeking that is closely tied to cigarette and alcohol experimentation. METHODS: We examined the contribution of candidate genes to social disinhibition among 1132 Mexican origin youth in Houston, Texas, adjusting for established demographic and psychosocial risk factors. Saliva samples were obtained at baseline in 2005-06, and social disinhibition and other psychosocial data were obtained in 2008-09. Participants were genotyped for 672 functional and tagging SNPs potentially related to sensation-seeking, risk-taking, smoking, and alcohol use. RESULTS: Six SNPs were significantly associated with social disinhibition scores, after controlling for false discovery and adjusting for population stratification and relevant demographic/psychosocial characteristics. Minor alleles for three of the SNPs (rs1998220 on OPRM1; rs9534511 on HTR2A; and rs4938056 on HTR3B) were associated with increased risk of social disinhibition, while minor alleles for the other three SNPs (rs1003921 on KCNC1; rs16116 downstream of NPY; and rs16870286 on LINC00518) exhibited a protective effect. Age, linguistic acculturation, thrill and adventure-seeking, and drug and alcohol-seeking were all significantly positively associated with increased risk of social disinhibition in a multivariable model (P < 0.001). CONCLUSIONS: These results add to our knowledge of genetic risk factors for social disinhibition. Additional research is needed to verify whether these SNPs are associated with social disinhibition among youth of different ethnicities and nationalities, and to elucidate whether and how these SNPs functionally contribute to social disinhibition.
Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Genótipo , Americanos Mexicanos/psicologia , Assunção de Riscos , Fumar/psicologia , Adolescente , Consumo de Bebidas Alcoólicas/genética , Criança , Feminino , Humanos , Masculino , Americanos Mexicanos/genética , Polimorfismo de Nucleotídeo Único , Fumar/genética , TexasRESUMO
PURPOSE: We examined the association of parental television (TV) rules and compliance with the American Academy of Pediatrics' (AAP) recommendations of Assuntos
Relações Pais-Filho
, Televisão/estatística & dados numéricos
, Negro ou Afro-Americano
, Criança
, Estudos Transversais
, Feminino
, Fidelidade a Diretrizes/estatística & dados numéricos
, Hispânico ou Latino
, Humanos
, Modelos Logísticos
, Masculino
, Áreas de Pobreza
, Serviços de Saúde Escolar
, Comportamento Sedentário
, Inquéritos e Questionários
, Texas
, Fatores de Tempo
, População Branca
RESUMO
BACKGROUND: People with less education in Europe, Asia, and the United States are at higher risk of mortality associated with daily and longer-term air pollution exposure. We examined whether educational level modified associations between mortality and ambient particulate pollution (PM10) in Latin America, using several timescales. METHODS: The study population included people who died during 1998-2002 in Mexico City, Mexico; Santiago, Chile; and São Paulo, Brazil. We fit city-specific robust Poisson regressions to daily deaths for nonexternal-cause mortality, and then stratified by age, sex, and educational attainment among adults older than age 21 years (none, some primary, some secondary, and high school degree or more). Predictor variables included a natural spline for temporal trend, linear PM10 and apparent temperature at matching lags, and day-of-week indicators. We evaluated PM10 for lags 0 and 1 day, and fit an unconstrained distributed lag model for cumulative 6-day effects. RESULTS: The effects of a 10-microg/m increment in lag 1 PM10 on all nonexternal-cause adult mortality were for Mexico City 0.39% (95% confidence interval = 0.13%-0.65%); São Paulo 1.04% (0.71%-1.38%); and for Santiago 0.61% (0.40%-0.83%). We found cumulative 6-day effects for adult mortality in Santiago (0.86% [0.48%-1.23%]) and São Paulo (1.38% [0.85%-1.91%]), but no consistent gradients by educational status. CONCLUSIONS: PM10 had important short- and intermediate-term effects on mortality in these Latin American cities, but associations did not differ consistently by educational level.
Assuntos
Poluição do Ar/efeitos adversos , Escolaridade , Mortalidade , Material Particulado/efeitos adversos , Adulto , Idoso , Brasil/epidemiologia , Chile/epidemiologia , Cidades , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Modelos Biológicos , Material Particulado/análise , Risco , Tempo (Meteorologia) , Adulto JovemRESUMO
BACKGROUND: Factors affecting vulnerability to heat-related mortality are not well understood. Identifying susceptible populations is of particular importance given anticipated rising temperatures from climatic change. METHODS: We investigated heat-related mortality for three Latin American cities (Mexico City, Mexico; São Paulo, Brazil; Santiago, Chile) using a case-crossover approach for 754 291 deaths from 1998 to 2002. We considered lagged exposures, confounding by air pollution, cause of death and susceptibilities by educational attainment, age and sex. RESULTS: Same and previous day apparent temperature were most strongly associated with mortality risk. Effect estimates remained positive though lowered after adjustment for ozone or PM(10). Susceptibility increased with age in all cities. The increase in mortality risk for those >or=65 comparing the 95th and 75th percentiles of same-day apparent temperature was 2.69% (95% CI: -2.06 to 7.88%) for Santiago, 6.51% (95% CI: 3.57-9.52%) for São Paulo and 3.22% (95% CI: 0.93-5.57%) for Mexico City. Patterns of vulnerability by education and sex differed across communities. Effect estimates were higher for women than men in Mexico City, and higher for men elsewhere, although results by sex were not appreciably different for any city. In São Paulo, those with less education were more susceptible, whereas no distinct patterns by education were observed in the other cities. CONCLUSIONS: Elevated temperatures are associated with mortality risk in these Latin American cities, with the strongest associations in São Paulo, the hottest city. The elderly are an important population for targeted prevention measures, but vulnerability by sex and education differed by city.