RESUMO
The inflammatory cytokine interleukin-1 (IL1) potentially plays a role in cognitive deterioration through pathology due to a dementing disorder or due to an aging process. Study of genetic variants in the IL1 genes has been mostly limited to diseases such as Alzheimer's, however, there may be benefit to studying a continuous measure of cognition. Using data from the Cardiovascular Health Study, we evaluate genetic variation in the genes encoding inflammatory agonists IL1A and IL1B, and the antagonist IL1RN, with repeated measures of global cognition (3MS) and processing speed (DSST), using mixed effects models. We found statistically significant minor allele SNP associations with baseline performance on the 3MS in the IL1RN gene for Caucasians (rs17042917: beta=0.47, 95%CI=0.09, 0.85, p=0.016; rs4251961: beta=-0.36, 95%CI=-0.13,-0.60, p=0.0027; rs931471: beta=0.39, 95%CI=0.13, 0.65, p=0.0032), and the IL1B gene for African Americans (rs1143627: beta=1.6, 95%CI=0.48, 2.8; p=0.006 and rs1143634: beta=2.09, 95%CI=0.39, 3.8; p=0.016). Associations appear to be weaker in a subgroup with higher education level. Upon removing those diagnosed with dementia, effect sizes and statistical significance attenuated. These results provide supporting evidence that genetic variants in IL1 genes may be involved in inflammatory-related lowered cognition, that higher education may modify genetic predisposition, and that these associations may be driven by a dementia process.
Assuntos
Cognição , Demência/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1alfa/genética , Interleucina-1beta/genética , Polimorfismo de Nucleotídeo Único , Negro ou Afro-Americano/genética , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/genética , Demência/epidemiologia , Demência/metabolismo , Escolaridade , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Desequilíbrio de Ligação , Estudos Longitudinais , Masculino , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia , População Branca/genéticaRESUMO
The goal of this study is to determine the linkage relationship between IgE levels and the 269 microsatellite markers using the Genetic Analysis Workshop 12 Busselton data set. Analyses were carried out using both traditional and new Haseman-Elston methods, the maximum likelihood quantitative trait locus estimation (MLE QTL) method and the nonparametric (NP QTL) method. Our analyses confirmed some of the signals reported by Daniels et al. [Nature 383:247-50, 1996]. We also observed that several significant signals reported in the original report became insignificant (D6S76 and D11S96) and several new signals showed up after the data were reanalyzed using the new Haseman-Elston method, the MLE QTL method, and the NP QTL method. Based on the original and the current analyses, we recommend that follow-up studies of three regions including D7S2250, FCER1B, D11S901, and six markers on chromosome 16 be given higher priority.
Assuntos
Asma/genética , Mapeamento Cromossômico/estatística & dados numéricos , Característica Quantitativa Herdável , Adulto , Asma/epidemiologia , Criança , Feminino , Frequência do Gene , Marcadores Genéticos/genética , Genética Populacional , Humanos , Imunoglobulina E/sangue , Funções Verossimilhança , Masculino , Repetições de Microssatélites/genética , Fenótipo , Austrália OcidentalRESUMO
A novel method for joint detection of association caused by linkage disequilibrium (LD) and estimation of both recombination fraction and linkage disequilibrium parameters was compared to several existing implementations of the transmission/disequilibrium test (TDT) and modifications of the TDT in the simulated genetic isolate data from Genetic Analysis Workshop 12. The first completely genotyped trio of affected child and parents was selected from each family in each replicate so that the TDT tests are valid tests of linkage and association, rather than being only valid as tests for linkage. In general, power to detect LD using the genome-wide scan markers was inadequate in the individual replicate samples, but the power was better when analyzing several SNP markers in candidate gene 1.
Assuntos
Genótipo , Desequilíbrio de Ligação , Modelos Genéticos , Adulto , Análise de Variância , Criança , Mapeamento Cromossômico/estatística & dados numéricos , Feminino , Marcadores Genéticos/genética , Predisposição Genética para Doença/genética , Humanos , Escore Lod , Masculino , Polimorfismo de Nucleotídeo Único , Característica Quantitativa HerdávelRESUMO
Reaction time (RT), discrimination sensitivity (d'), and the brainstem frequency-following response (FFR) were recorded in 32 subjects performing a selective attention task. Auditory stimuli were a 400 Hz pure tone and a complex "missing fundamental" (MF) presented dichotically to separate ears (channels). In two tasks, infrequent target stimuli were either of lower intensity or greater duration than standard stimuli. Behavioral results showed consistently better performance (faster RTs and higher d' scores) in the duration task, and better overall detection of MF targets. FFR attention effects were evidenced by differing amplitudes in attend and ignore conditions. Amplitudes in the attended channel were larger to MF stimuli in both tasks, and to the tone stimulus in the duration task. Responses to tone in the intensity task, however, were lowest when the channel was attended, perhaps reflecting some property of greater task difficulty. The demonstration of FFR amplitude differences between attended and ignored channels suggests that selective attention can modify brainstem evoked responses in humans.
