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Rationale: The 17q12-21.1 locus is one of the most highly replicated genetic associations with asthma. Individuals of African descent have lower linkage disequilibrium in this region, which could facilitate identifying causal variants.Objectives: To identify functional variants at 17q12-21.1 associated with early-onset asthma among African American individuals.Methods: We evaluated African American participants from SAPPHIRE (Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity) (n = 1,940), SAGE II (Study of African Americans, Asthma, Genes and Environment) (n = 885), and GCPD-A (Study of the Genetic Causes of Complex Pediatric Disorders-Asthma) (n = 2,805). Associations with asthma onset at ages under 5 years were meta-analyzed across cohorts. The lead signal was reevaluated considering haplotypes informed by genetic ancestry (i.e., African vs. European). Both an expression-quantitative trait locus analysis and a phenome-wide association study were performed on the lead variant.Measurements and Main Results: The meta-analyzed results from SAPPHIRE, SAGE II, and the GCPD-A identified rs11078928 as the top association for early-onset asthma. A haplotype analysis suggested that the asthma association partitioned most closely with the rs11078928 genotype. Genetic ancestry did not appear to influence the effect of this variant. In the expression-quantitative trait locus analysis, rs11078928 was related to alternative splicing of GSDMB (gasdermin-B) transcripts. The phenome-wide association study of rs11078928 suggested that this variant was predominantly associated with asthma and asthma-associated symptoms.Conclusions: A splice-acceptor polymorphism appears to be a causal variant for asthma at the 17q12-21.1 locus. This variant appears to have the same magnitude of effect in individuals of African and European descent. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most prevalent form of dementia in the world, which is characterised by the loss of neurones and the build-up of plaques in the brain, causing progressive symptoms of memory loss and confusion. Although definite diagnosis is only possible by necropsy, differential diagnosis with other types of dementia is still needed. An electroencephalogram (EEG) is a cheap, portable, non-invasive method to record brain signals. Previous studies with non-linear signal processing methods have shown changes in the EEG due to AD, which is characterised reduced complexity and increased regularity. EEGs from 11 AD patients and 11 age-matched control subjects were analysed with Fuzzy Entropy (FuzzyEn), a non-linear method that was introduced as an improvement over the frequently used Approximate Entropy (ApEn) and Sample Entropy (SampEn) algorithms. AD patients had significantly lower FuzzyEn values than control subjects (p < 0.01) at electrodes T6, P3, P4, O1, and O2. Furthermore, when diagnostic accuracy was calculated using Receiver Operating Characteristic (ROC) curves, FuzzyEn outperformed both ApEn and SampEn, reaching a maximum accuracy of 86.36%. These results suggest that FuzzyEn could increase the insight into brain dysfunction in AD, providing potentially useful diagnostic information. However, results depend heavily on the input parameters that are used to compute FuzzyEn. [ABSTRACT FROM AUTHOR]

The analysis of electroencephalograms (EEGs) of patients with Alzheimer's disease (AD) could contribute to the diagnosis of this dementia. In this study, a new non-linear signal processing metric, distance-based Lempel-Ziv complexity (dLZC), is introduced to characterise changes between pairs of electrodes in EEGs in AD. When complexity in each signal arises from different sub-sequences, dLZC would be greater than when similar sub-sequences are present in each signal. EEGs from 11 AD patients and 11 age-matched control subjects were analysed. The dLZC values for AD patients were lower than for control subjects for most electrode pairs, with statistically significant differences (p < 0.01, Student's t-test) in 17 electrode pairs in the distant left, local posterior left, and interhemispheric regions. Maximum diagnostic accuracies with leave-one-out cross-validation were 77.27% for subject-based classification and 78.25% for epoch-based classification. These findings suggest not only that EEGs from AD patients are less complex than those from controls, but also that the richness of the information contained in pairs of EEGs from patients is also lower than in age-matched controls. The analysis of EEGs in AD with dLZC may increase the insight into brain dysfunction, providing complementary information to that obtained with other complexity and synchrony methods. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a degenerative brain disorder leading to memory loss and changes in other cognitive abilities. The complexity of electroencephalogram (EEG) signals may help to characterise AD. To this end, we propose an extension of multiscale entropy based on variance (MSEσ2) to multichannel signals, termed multivariate MSEσ2 (mvMSEσ2), to take into account both the spatial and time domains of time series. Then, we investigate the mvMSEσ2 of EEGs at different frequency bands, including the broadband signals filtered between 1 and 40 Hz, θ, α, and β bands, and compare it with the previously-proposed multiscale entropy based on mean (MSE), multivariate MSEμ (mvMSEμ), and MSEσ2, to distinguish different kinds of dynamical properties of the spread and the mean in the signals. Results from 11 AD patients and 11 age-matched controls suggest that the presence of broadband activity of EEGs is required for a proper evaluation of complexity. MSEσ2 and mvMSEσ2 results, showing a loss of complexity in AD signals, led to smaller p-values in comparison with MSEμ and mvMSEμ ones, suggesting that the variance-based MSE and mvMSE can characterise changes in EEGs as a result of AD in a more detailed way. The p-values for the slope values of the mvMSE curves were smaller than for MSE at large scale factors, also showing the possible usefulness of multivariate techniques. [ABSTRACT FROM AUTHOR]

Understanding the dynamics of brain activity manifested in the EEG, local field potentials (LFP), and neuronal spiking is essential for explaining their underlying mechanisms and physiological significance. Much has been learned about sleep regulation using conventional EEG power spectrum, coherence, and period-amplitude analyses, which focus primarily on frequency and amplitude characteristics of the signals and on their spatio-temporal synchronicity. However, little is known about the effects of ongoing brain state or preceding sleep-wake history on the nonlinear dynamics of brain activity. Recent advances in developing novel mathematical approaches for investigating temporal structure of brain activity based on such measures, as Lempel-Ziv complexity (LZC) can provide insights that go beyond those obtained with conventional techniques of signal analysis. Here, we used extensive data sets obtained in spontaneously awake and sleeping adult male laboratory rats, as well as during and after sleep deprivation, to perform a detailed analysis of cortical LFP and neuronal activity with LZC approach. We found that activated brain states--waking and rapid eye movement (REM) sleep are characterized by higher LZC compared with non-rapid eye movement (NREM) sleep. Notably, LZC values derived from the LFP were especially low during early NREM sleep after sleep deprivation and toward the middle of individual NREM sleep episodes. We conclude that LZC is an important and yet largely unexplored measure with a high potential for investigating neurophysiological mechanisms of brain activity in health and disease. [ABSTRACT FROM AUTHOR]