Proceedings of the COST action BM1407 inaugural conference BEAT-PCD: translational research in primary ciliary dyskinesia - bench, bedside, and population perspectives
In this report, we summarize the meeting, highlight developments, and discuss open questions thereby documenting ongoing development s in the field of PCD research. (Source: BMC Proceedings)
Source: BMC Proceedings - October 31, 2016 Category: Biomedical Science Source Type: research
The activity of the Research Investments in Global Health study and ways forward within the global funding and policy landscape
AbstractThe Research Investments in Global Health (ResIn,www.researchinvestments.org) study analyses funding trends in health research, with a predominant focus on infectious diseases. Since October 2015, the project is funded by the Bill& Melinda Gates Foundation and is now based at the University of Southampton in the UK. In 2016, Public Policy@Southampton provided ResIn with a small grant to explore developing links with policy, funding and research stakeholders with an interest in global health. Three meetings were organised in London (Wellcome Trust, 25 May 2016), Brussels (UK Research Office, 2 June 2016), and Ge...
Source: BMC Proceedings - October 9, 2016 Category: Biomedical Science Source Type: research
On combining family- and population-based sequencing data
In this study, we investigated the efficient combination of population-based and family-based sequencing data to evaluate best practices using the Genetic Analysis Workshop 19 (GAW19) data set. Because one design employed whole genome sequencing and the other whole exome sequencing, we examined variants overlapping both data sets. We used the family-based sequence kernel association test (famSKAT) to analyze the family- and population-based data sets separately as well as with a combined data set. These were compared against meta-analysis. Using the combined data, we showed that famSKAT has high power to detect association...
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Comparing machine learning and logistic regression methods for predicting hypertension using a combination of gene expression and next-generation sequencing data
AbstractMachine learning methods continue to show promise in the analysis of data from genetic association studies because of the high number of variables relative to the number of observations. However, few best practices exist for the application of these methods. We extend a recently proposed supervised machine learning approach for predicting disease risk by genotypes to be able to incorporate gene expression data and rare variants. We then apply 2 different versions of the approach (radial and linear support vector machines) to simulated data from Genetic Analysis Workshop 19 and compare performance to logistic regres...
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Independent test assessment using the extreme value distribution theory
In this report, we examine 2 alternative approaches to improve the statistical power of a whole genome association study to detect reliable genetic association s. The approaches were tested using the Genetic Analysis Workshop 19 (GAW19) whole genome sequencing data. The first tested method estimates the real number of effective independent tests actually being performed in whole genome association project by the use of an extreme value distribution and a s et of phenotype simulations. Given the familiar nature of the GAW19 data and the finite number of pedigree founders in the sample, the number of correlations between gen...
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Identification of interactions using model-based multifactor dimensionality reduction
ConclusionsThe considered filtering methods seem not to be appropriate to use with MB-MDR. LD pruning is further quality control to be incorporated, which can reduce the combinatorial burden by removing redundant SNPs. (Source: BMC Proceedings)
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Identification of low frequency and rare variants for hypertension using sparse-data methods
In this study, we conduct association analyses of hypertension status in the cohort of 1943 unrelated Mexican Americans provided by Genetic Analysis Workshop 19, focusing on exonic variants inMAP4 on chromosome 3. Our primary interest is to compare the performance of standard and sparse-data approaches for single-variant tests and variant-collapsing tests for sets of rare and low-frequency variants. We analyze both the real and the simulated phenotypes. (Source: BMC Proceedings)
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Identity-by-descent mapping for diastolic blood pressure in unrelated Mexican Americans
We presented a mapping strategy which combined a population-based IBD mapping method with sequence data analyses. One gene was located at a chromosomal region identified by this method for DBP. However, further study with a large sample size is needed to assess this result. (Source: BMC Proceedings)
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test
We present a novel approach to detect potentialcis-acting regulatory loci that combines the functional potential, an empirical DNase-seq based estimate of the allele-specificity of DNase-I hypersensitivity sites, with kernel-based variance component association analyses against expression phenotypes. To test our method we used public ENCODE whole genome DNase-I sequencing data, from a single sample, to estimate the functional potentials of the subset of 10,552 noncoding heterozygous single-nucleotide polymorphisms (SNPs) that were also present in the Genetic Analysis Workshop 19 (GAW19) family-based data set. We then built...
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Comparing strategies for combined testing of rare and common variants in whole sequence and genome-wide genotype data
AbstractWe used our extension of the kernel score test to family data to analyze real and simulated baseline systolic blood pressure in extended pedigrees. We compared the power for different kernels and for different weightings of genetic markers. Moreover, we compared the power of rare and common markers with 3 strategies for joint testing and on marker panels with different densities. Marker weights had much greater influence on power than the kernel chosen. Inverse minor allele frequency weights often increased power on common markers but could decrease power on rare markers. Furthermore, defining the gene region based...
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Association of polymorphisms in the aldosterone-regulated sodium reabsorption pathway with blood pressure among Hispanics
ConclusionThe findings from this study show that pathway-based analytical approach targeting known biological pathways can be useful in identification of disease-associated variants that are otherwise undetectable by GWAS. The approach takes advantage of the assumption of nonindependence of variants within and across pathway genes which leads to reduced penalty of multiple testing and thus less-stringent statistical significance threshold. (Source: BMC Proceedings)
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Prioritization of family member sequencing for the detection of rare variants
ConclusionsTaking the additional steps to select the optimal cases and controls from large family data sets can help ensure that only informative individuals are included in analysis and may improve the ability to detect rare variants. (Source: BMC Proceedings)
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Analysis of gene expression to predict dynamics of future hypertension incidence in type 2 diabetic patients
ConclusionsThere is no obvious mechanism that links all detected genes with dynamics of hypertension incidence. Identification of possible connection with hypertension needs further investigation. (Source: BMC Proceedings)
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Structural equation modeling with latent variables for longitudinal blood pressure traits using general pedigrees
AbstractStructural equation modeling (SEM) has been used in a wide range of applied sciences including genetic analysis. The recently developed R package,strum, implements a framework for SEM for general pedigree data. We explored different SEM techniques usingstrum to analyze the multivariate longitudinal data and to ultimately test the association of genotypes on blood pressure traits. The quantitative blood pressure (BP) traits, systolic BP (SBP) and diastolic BP (DBP) were analyzed as the main traits of interest with age, sex, and smoking status as covariates. The single nucleotide polymorphism (SNP) genotype informati...
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
Genetic complexity at expression quantitative trait loci
ConclusionseQTL exhibit substantial genetic complexity among and within pedigrees. (Source: BMC Proceedings)
Source: BMC Proceedings - September 30, 2016 Category: Biomedical Science Source Type: research
