BMC Proceedings

http://link.springer.com/journal/12919

List of Papers (Total 3,355)

Addressing challenges in children’s mental health in disaster-affected areas in Japan and the Philippines – highlights of the training program by the National Center for Global Health and Medicine

Background and purposeNatural disasters such as earthquakes, typhoons, floods, and volcanic eruptions frequently occur in Republic of Philippines and mental health care for children affected by these natural disasters is a major public health concern. Aiming to train health professionals on children’s mental health, to conduct a situational analysis to identify the local needs...

Cholera prevention and control in Asian countries

Cholera remains a major public health problem in many countries. Poor sanitation and inappropriate clean water supply, insufficient health literacy and community mobilization, absence of national plans and cross-border collaborations are major factors impeding optimal control of cholera in endemic countries.In March 2017, a group of experts from 10 Asian cholera-prone countries...

Simulation of a medication and methylation effects on triglycerides in the Genetic Analysis Workshop 20

The GAW20 simulation data set is based upon the companion Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study fenofibrate clinical trial data set that forms the real data example for GAW20. The simulated data problem consists of 200 simulated replications of what might happen if we were to repeat the GOLDN clinical trial 200 independent times, for these exact same...

Integrative methylation score to identify epigenetic modifications associated with lipid changes resulting from fenofibrate treatment in families

Epigenome-wide association studies (EWAS) have traditionally focused on the association test of single epigenetic markers with complex traits. However, it is possible that multiple cytosine-phosphate-guanine (CpG) sites at the same locus could jointly exert their effects on human traits. Therefore, a region-based test that combines multiple markers could be more powerful. We used...

An adaptive gene-based test for methylation data

DNA methylation plays an important role in normal human development and disease. In epigenome-wide association studies (EWAS), a univariate test for association between a phenotype and each cytosine-phosphate-guanine (CpG) site has been widely used. Given the number of CpG sites tested in EWAS, a stringent significance cutoff is required to adjust for multiple testing; in...

Reliability of genomic predictions of complex human phenotypes

Genome-wide association studies have helped us identify a wealth of genetic variants associated with complex human phenotypes. Because most variants explain a small portion of the total phenotypic variation, however, marker-based studies remain limited in their ability to predict such phenotypes. Here, we show how modern statistical genetic techniques borrowed from animal...

Disentangling associations between DNA methylation and blood lipids: a Mendelian randomization approach

BackgroundDNA methylation is an epigenetic mechanism that has been proposed as a possible link between genetic and environmental determinants of disease. Prior studies reported robust associations between the methylation of specific cytosine-phosphate-guanine (CpG) sites and plasma lipids, namely triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C). However, the...

Detection and analysis of CpG sites with multimodal DNA methylation level distributions and their relationships with SNPs

DNA methylation levels at cytosine-phosphate-guanine (CpG) sites with multimodal distributions among different samples have been reported recently. One possible explanation for such variability is that genetic variants might affect epigenetic variation. One obvious case is that mutations such as single-nucleotide polymorphisms (SNPs) interrupt CpG sites, resulting in different...

GAW20: methods and strategies for the new frontiers of epigenetics and pharmacogenomics

GAW20 provided a platform for developing and evaluating statistical methods to analyze human lipid-related phenotypes, DNA methylation, and single-nucleotide markers in a study involving a pharmaceutical intervention. In this article, we present an overview of the data sets and the contributions analyzing these data. The data, donated by the Genetics of Lipid Lowering Drugs and...

Integrating epigenetic, genetic, and phenotypic data to uncover gene-region associations with triglycerides in the GOLDN study

BackgroundThere has been significant interest in investigating genome-wide and epigenome-wide associations with lipids. Testing at the gene or region level may improve power in such studies.MethodsWe analyze chromosome 11 cytosine-phosphate-guanine (CpG) methylation levels and single-nucleotide polymorphism (SNP) genotypes from the original Genetics of Lipid Lowering Drugs and...

Genome-wide association study for multiple phenotype analysis

Genome-wide association studies often collect multiple phenotypes for complex diseases. Multivariate joint analyses have higher power to detect genetic variants compared with the marginal analysis of each phenotype and are also able to identify loci with pleiotropic effects. We extend the unified score-based association test to incorporate family structure, apply different...

Transmission-based association mapping of triglyceride levels in a longitudinal framework using quasi-likelihood

Complex genetic traits are often characterized by multiple quantitative phenotypes. Because values of such phenotypes vary over time, it is thought that analyses of longitudinal data on the phenotypes may lead to increased power in detecting genetic association. In this paper, we extend a transmission-based association test applying quasi-likelihood that has been developed by us...

Modeling methylation data as an additional genetic variance component

High-throughput platforms allow the characterization of thousands of previously known methylation sites. These platforms have great potential for investigating the epigenetic effects that are partially responsible for gene expression control. Methylation sites provide a bridge for the investigation of real-time environmental contributions on genomic events by the alteration of...

Coping with family structure in genome-wide association studies: a comparative evaluation

In this paper, a fully statistical investigation of the control of family structure as random effects is analyzed and discussed, using both the genome-wide association studies (GWAS) data and simulated data. Three modeling strategies are proposed and the analysis results suggest the hybrid use of results from all possible models should be combined in practice.

A Bayesian mixed modeling approach for estimating heritability

BackgroundA Bayesian mixed model approach using integrated nested Laplace approximations (INLA) allows us to construct flexible models that can account for pedigree structure. Using these models, we estimate genome-wide patterns of DNA methylation heritability (h2), which are currently not well understood, as well as h2 of blood lipid measurements.MethodsWe included individuals...

Epigenome wide association study of SNP–CpG interactions on changes in triglyceride levels after pharmaceutical intervention: a GAW20 analysis

In the search for an understanding of how genetic variation contributes to the heritability of common human disease, the potential role of epigenetic factors, such as methylation, is being explored with increasing frequency. Although standard analyses test for associations between methylation levels at individual cytosine-phosphate-guanine (CpG) sites and phenotypes of interest...

Evaluating the performance of gene-based tests of genetic association when testing for association between methylation and change in triglyceride levels at GAW20

Although methylation data continues to rise in popularity, much is still unknown about how to best analyze methylation data in genome-wide analysis contexts. Given continuing interest in gene-based tests for next-generation sequencing data, we evaluated the performance of novel gene-based test statistics on simulated data from GAW20. Our analysis suggests that most of the gene...

Genome-wide linkage scan for loci influencing plasma triglyceride levels

We conducted a genome-wide linkage scan to detect loci that influence the levels of fasting triglycerides in plasma. Fasting triglyceride levels were available at 4 time points (visits), 2 pre- and 2 post-fenofibrate intervention. Multipoint identity-by-descent (MIBD) matrices were derived from genotypes using IBDLD. Variance-component linkage analyses were then conducted using...

Direct and indirect genetic effects on triglycerides through omics and correlated phenotypes

Even though there has been great success in identifying lipid-associated single-nucleotide polymorphisms (SNPs), the mechanisms through which the SNPs act on each trait are poorly understood. The emergence of large, complex biological data sets in well-characterized cohort studies offers an opportunity to investigate the genetic effects on trait variability as a way of informing...

Methods for detecting methylation by SNP interaction in GAW20 simulation

To examine whether single-nucleotide polymorphism (SNP) by methylation interactions can be detected, we analyzed GAW20 simulated triglycerides at visits 3 and 4 against baseline (visits 1 and 2) under 4 general linear models and 2 tree-based models in 200 replications of a sample of 680 individuals. Effects for SNPs, methylation cytosine-phosphate-guanine (CpG) effects, and...

Analysis of genetic and nongenetic factors influencing triglycerides-lowering drug effects based on paired observations

Obesity is a risk factor for heart disease, stroke, diabetes, high blood pressure, and other chronic diseases. Some drugs, including fenofibrate, are used to treat obesity or excessive weight by lowering the level of specific triglycerides. However, different groups have different drug sensitivities and, consequently, there are differences in drug effects. In this study, we...

Heritability and genetic associations of triglyceride and HDL-C levels using pedigree-based and empirical kinships

The heritability of a phenotype is an estimation of the percent of variance in that phenotype that is attributable to additive genetic factors. Heritability is optimally estimated in family-based sample populations. Traditionally, this involves use of a pedigree-based kinship coefficient generated from the collected genealogical relationships between family members. An...

Family-based genome-wide association of inflammation biomarkers and fenofibrate treatment response in the GOLDN study

In this paper we analyzed whole-genome genetic information provided by GAW20 from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study for family data. Lipid levels such as triglycerides (TGs) and high-density lipoprotein (HDL) are measured at different time points before and after administration of an anti-inflammatory drug fenofibrate. Apart from that, the data...

CpG-set association assessment of lipid concentration changes and DNA methylation

Epigenome association studies that test a large number of methylation sites suffer from stringent multiple-testing corrections. This study’s goals were to investigate region-based associations between DNA methylation sites and lipid-level changes in response to the treatment with fenofibrate in the GAW20 data and to investigate whether improvements in power could be obtained by...