1,091 results match your criteria BMC proceedings[Journal]


Proceedings of the 3rd BEAT-PCD Conference and 4th PCD Training School.

BMC Proc 2018 18;12(Suppl 16):64. Epub 2018 Dec 18.

Danish PCD & Child Centre, CF Centre Copenhagen, Paediatric Pulmonary Service, ERN Accredited, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Denmark.

Primary ciliary dyskinesia (PCD) is a chronic suppurative airways disease that is usually recessively inherited and has marked clinical phenotypic heterogeneity. Classic symptoms include neonatal respiratory distress, chronic rhinitis since early childhood, chronic otitis media, recurrent airway infections leading to bronchiectasis, chronic sinusitis, laterality defects with and without congenital heart disease including abnormal situs in approximately 50% of the cases, and male infertility. Lung function deteriorates progressively from childhood throughout life. Read More

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http://dx.doi.org/10.1186/s12919-018-0161-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297936PMC
December 2018
1 Read

Cholera prevention and control in Asian countries.

BMC Proc 2018 7;12(Suppl 13):62. Epub 2018 Dec 7.

26World Health Organization, New Delhi, India.

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 that belong to the Initiative against Diarrheal and Enteric Diseases in Africa and Asia (IDEA), together with representatives from the World Health Organization, the US National Institutes of Health, International Vaccine Institute, Agence de médecine préventive, NGOs (Save the Children) and UNICEF, met in Hanoi (Vietnam) to share progress in terms of prevention and control interventions on water, sanitation and hygiene (WASH), surveillance and oral cholera vaccine use. Read More

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http://dx.doi.org/10.1186/s12919-018-0158-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284268PMC
December 2018
4 Reads

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.

BMC Proc 2018 19;12(Suppl 14):65. Epub 2018 Dec 19.

10Department of Psychiatry, Kohondai Hospital, National Center for Global Health and Medicine, Ichikawa, Japan.

Background And Purpose: Natural 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 and resources for children's mental health, and to propose a mental health program for children that can be transferred from Japan to the Philippines, the National Center for Global Health and Medicine (NCGM) conducted a training program for children's mental health in disaster-affected areas in Japan and the Philippines in June, October, and December, 2017. The training was organized by NCGM for the Program for International Promotion of Japan's Healthcare Technologies and Services funded by Ministry of Health, Labour, & Welfare, Japan in relation to the Memorandum of Understanding in the Field of Healthcare between NCGM in Japan and University of the Philippines Manila, College of Public Health. Read More

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http://dx.doi.org/10.1186/s12919-018-0159-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299512PMC
December 2018
2 Reads

Conclusions of the digital health hub of the Transform Africa Summit (2018): strong government leadership and public-private-partnerships are key prerequisites for sustainable scale up of digital health in Africa.

BMC Proc 2018 15;12(Suppl 11):17. Epub 2018 Aug 15.

WHO Country Office, Kigali, Rwanda.

Background: The use of digital technologies to improve access to health is gaining momentum in Africa. This is more pertinent with the increasing penetration of mobile phone technology and internet use, and calls for innovative strategies to support implementation of the health-related Sustainable Development Goals and Universal Health Coverage on the continent. However, the huge potential benefits of digital health to advance health services delivery in Africa is yet to be fully harnessed due to critical challenges such as proliferation of pilot projects, poor coordination, inadequate preparedness of the African health workforce for digital health, lack of interoperability and inadequate sustainable financing, among others. Read More

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http://dx.doi.org/10.1186/s12919-018-0156-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117634PMC
August 2018
7 Reads

Learning best-practices in journalology: course description and attendee insights into the inaugural EQUATOR Canada Publication School.

BMC Proc 2018 23;12(Suppl 10):18. Epub 2018 Aug 23.

2Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Canada.

Background And Purpose: Dissemination of research results is a key component of the research continuum and is commonly achieved through publication in peer-reviewed academic journals. However, issues of poor quality reporting in the research literature are well documented. A lack of formal training in journalology (i. Read More

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http://dx.doi.org/10.1186/s12919-018-0155-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117632PMC
August 2018
15 Reads

An adaptive gene-based test for methylation data.

BMC Proc 2018 17;12(Suppl 9):60. Epub 2018 Sep 17.

Division of Biostatistics, University of Minnesota, 420 Delaware St SE, Minneapolis, MN 55455 USA.

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 addition, multiple nearby CpG sites may be associated with the phenotype, which is ignored by a univariate test. Read More

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http://dx.doi.org/10.1186/s12919-018-0126-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157100PMC
September 2018
1 Read

Identification of epistatic interactions between the human RNA demethylases FTO and ALKBH5 with gene set enrichment analysis informed by differential methylation.

BMC Proc 2018 17;12(Suppl 9):59. Epub 2018 Sep 17.

Institute for Biomedical Informatics, Richards Medical Research Laboratories, Perelman School of Medicine, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, PA 19104 USA.

The Genetic Analysis Workshop (GAW) presents an opportunity to collaboratively evaluate methodology relevant to current issues in genetic epidemiology. The GAW20 data combine real clinical trial data with fictitious epigenetic drug response endpoints. Considering the evidence suggesting that networks of interactions between many genes underlie complex phenotypes, we utilize differential methylation status to identify a relevant gene set for enrichment analysis and use this to infer potential biological function underlying drug response. Read More

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http://dx.doi.org/10.1186/s12919-018-0122-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157145PMC
September 2018
2 Reads

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

BMC Proc 2018 17;12(Suppl 9):58. Epub 2018 Sep 17.

2Department of Mathematics and Statistics, Dordt College, 498 4th Ave. NE, Sioux Center, IA 51250 USA.

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, some investigators have begun testing for methylation and how methylation may modulate the effects of genetic polymorphisms on phenotypes. In our analysis, we used both a genome-wide and candidate gene approach to investigate potential single-nucleotide polymorphism (SNP)-CpG interactions on changes in triglyceride levels. Read More

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http://dx.doi.org/10.1186/s12919-018-0144-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157099PMC
September 2018
9 Reads

Evaluation of a phenotype imputation approach using GAW20 simulated data.

BMC Proc 2018 17;12(Suppl 9):56. Epub 2018 Sep 17.

Department of Biostatistics, Boston University School of Public Health, 801 Massachusetts Ave 3rd Floor, Boston, MA 02118 USA.

Statistical power, which is the probability of correctly rejecting a false null hypothesis, is a limitation of genome-wide association studies (GWAS). Sample size is a major component of statistical power that can be easily affected by missingness in phenotypic data and restrain the ability to detect associated single-nucleotide polymorphisms (SNPs) with small effect sizes. Although some phenotypes are hard to collect because of cost and loss to follow-up, correlated phenotypes that are easily collected can be leveraged for association analysis. Read More

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http://dx.doi.org/10.1186/s12919-018-0134-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157247PMC
September 2018
2 Reads

Genome-wide linkage scan for loci influencing plasma triglyceride levels.

BMC Proc 2018 17;12(Suppl 9):52. Epub 2018 Sep 17.

2Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000 Australia.

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. Read More

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http://dx.doi.org/10.1186/s12919-018-0137-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157192PMC
September 2018
9 Reads

Reliability of genomic predictions of complex human phenotypes.

BMC Proc 2018 17;12(Suppl 9):51. Epub 2018 Sep 17.

1South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, One West University Blvd. Modular Building #100, Brownsville, TX 78250 USA.

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 breeding can be employed to increase the accuracy of genomic prediction of complex phenotypes and the power of genetic mapping studies. Read More

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http://dx.doi.org/10.1186/s12919-018-0138-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157117PMC
September 2018
16 Reads

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

BMC Proc 2018 17;12(Suppl 9):50. Epub 2018 Sep 17.

1Department of Mathematics and Statistics, Dordt College, 498 4th Ave. NE, Sioux Center, IA 51250 USA.

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-based tests are detecting real signals and maintaining the Type I error rate. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
Publisher Site
http://dx.doi.org/10.1186/s12919-018-0124-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157195PMC
September 2018
2 Reads

Relating drug response to epigenetic and genetic markers using a region-based kernel score test.

BMC Proc 2018 17;12(Suppl 9):47. Epub 2018 Sep 17.

Department of Genetic Epidemiology, University Medical Center, Georg-August University Göttingen, Humboldtallee 32, 37073 Göttingen, Germany.

In GAW20, we investigated the association of specific genetic regions of interest (ROIs) with log-transformed triglyceride (TG) levels following lipid-lowering medication using epigenetic and genetic markers. The goal was to incorporate kernels for cytosine-phosphate-guanine (CpG) markers and compare the kernels to a purely parametric model. Post-treatment TG levels were investigated for post-methylation data at CpG sites and region-specific SNPs and adjusted for pre-treatment TG levels and age, in independent individuals only (real data:  = 150; simulated data, replicate 84:  = 111). Read More

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http://dx.doi.org/10.1186/s12919-018-0154-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157113PMC
September 2018
1 Read

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

BMC Proc 2018 17;12(Suppl 9):46. Epub 2018 Sep 17.

1Department of Statistics, University of Nebraska, 340 Hardin Hall North Wing, Lincoln, NE 68588 USA.

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. Read More

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http://dx.doi.org/10.1186/s12919-018-0153-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157156PMC
September 2018
1 Read

An efficient analytic approach in genome-wide identification of methylation quantitative trait loci response to fenofibrate treatment.

BMC Proc 2018 17;12(Suppl 9):44. Epub 2018 Sep 17.

3Department of Biostatistics, Boston University School of Public Health, Boston University, 715 Albany St, Boston, MA 02118 USA.

Background: The study of DNA methylation quantitative trait loci (meQTLs) helps dissect regulatory mechanisms underlying genetic associations of human diseases. In this study, we conducted the first genome-wide examination of genetic drivers of methylation variation in response to a triglyceride-lowering treatment with fenofibrate (response-meQTL) by using an efficient analytic approach.

Methods: Subjects ( = 429) from the GAW20 real data set with genotype and both pre- (visit 2) and post- (visit 4) fenofibrate treatment methylation measurements were included. Read More

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http://dx.doi.org/10.1186/s12919-018-0152-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157188PMC
September 2018
3 Reads

Identifying fenofibrate responsive CpG sites.

BMC Proc 2018 17;12(Suppl 9):43. Epub 2018 Sep 17.

Department of Human Genetics, David Geffen School of Medicine, University of California at Los Angeles, 695 Charles E. Young Dr. South, Los Angeles, CA USA.

As part of GAW20, we analyzed the familiality and variability of methylation to identify cytosine-phosphate-guanine (CpG) sites responsive to treatment with fenofibrate. Methylation was measured at approximately 450,000 sites in pedigree members, prior to and after 3 weeks of treatment. Initially, we aimed to identify responsive sites by analyzing the pre- and posttreatment methylation changes within individuals, but these data exhibited a confounding treatment/batch effect. Read More

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http://dx.doi.org/10.1186/s12919-018-0148-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157159PMC
September 2018
2 Reads

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

BMC Proc 2018 17;12(Suppl 9):41. Epub 2018 Sep 17.

Human Genetics Unit, Indian Statistical Institute, 203 B T Road, Kolkata, 700108 India.

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 contain some covariates and whole-genome genotype information. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
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http://dx.doi.org/10.1186/s12919-018-0146-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157183PMC
September 2018
5 Reads

Analysis of genotype by methylation interactions through sparsity-inducing regularized regression.

BMC Proc 2018 17;12(Suppl 9):40. Epub 2018 Sep 17.

Department of Statistics, Columbia University, 1255 Amsterdam Avenue, New York, NY 10027 USA.

In this paper, we consider the use of the least absolute shrinkage and selection operator (LASSO)-type regression techniques to detect important genetic or epigenetic loci in genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS). We demonstrate how these techniques can be adapted to provide quantifiable uncertainty using stability selection, including explicit control of the family-wise error rate. We also consider variants of the LASSO, such as the group LASSO, to study genetic and epigenetic interactions. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
Publisher Site
http://dx.doi.org/10.1186/s12919-018-0145-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157158PMC
September 2018
3 Reads

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

BMC Proc 2018 17;12(Suppl 9):39. Epub 2018 Sep 17.

Human Genetics Unit, Indian Statistical Institute, 203 BT Road, Kolkata, India.

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 to the longitudinal framework and to carry out a genome-wide association analysis of triglyceride levels based on the data provided in GAW20. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
Publisher Site
http://dx.doi.org/10.1186/s12919-018-0147-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157161PMC
September 2018
14 Reads

Using penalized regression to predict phenotype from SNP data.

BMC Proc 2018 17;12(Suppl 9):38. Epub 2018 Sep 17.

Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne, NE1 3BZ UK.

Background: In a typical genome-enabled prediction problem there are many more predictor variables than response variables. This prohibits the application of multiple linear regression, because the unique ordinary least squares estimators of the regression coefficients are not defined. To overcome this problem, penalized regression methods have been proposed, aiming at shrinking the coefficients toward zero. Read More

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http://dx.doi.org/10.1186/s12919-018-0149-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157193PMC
September 2018
2 Reads

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

Authors:
Ke Hu Jing Li

BMC Proc 2018 17;12(Suppl 9):36. Epub 2018 Sep 17.

Department of Electrical Engineering, Computer Science Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106 USA.

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 DNA methylation levels for different genotypes. Read More

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http://dx.doi.org/10.1186/s12919-018-0141-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157119PMC
September 2018
12 Reads

Data for GAW20: genome-wide DNA sequence variation and epigenome-wide DNA methylation before and after fenofibrate treatment in a family study of metabolic phenotypes.

BMC Proc 2018 17;12(Suppl 9):35. Epub 2018 Sep 17.

5College of Public Health, University of Kentucky, 111 Washington Ave, Lexington, KY 40536 USA.

GAW20 provided participants with an opportunity to comprehensively examine genetic and epigenetic variation among related individuals in the context of drug treatment response. GAW20 used data from 188 families ( = 1105) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (clinicaltrials.gov identifier NCT00083369), which included CD4+ T-cell DNA methylation at 463,995 cytosine-phosphate-guanine (CpG) sites measured before and after a 3-week treatment with fenofibrate, single-nucleotide variation at 906,600 loci, metabolic syndrome components ascertained before and after the drug intervention, and relevant covariates. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
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http://dx.doi.org/10.1186/s12919-018-0114-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157153PMC
September 2018
3 Reads

Genome-wide analysis in multiple-case families: assessing the relationship between triglyceride and methylation.

BMC Proc 2018 17;12(Suppl 9):33. Epub 2018 Sep 17.

2Department of Statistics, University of Leeds, Leeds, LS2 9JT UK.

The main goal of this paper is to estimate the effect of triglyceride levels on methylation of cytosine-phosphate-guanine (CpG) sites in multiple-case families. These families are selected because they have 2 or more cases of metabolic syndrome (primary phenotype). The methylations at the CpG sites are the secondary phenotypes. Read More

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http://dx.doi.org/10.1186/s12919-018-0123-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157284PMC
September 2018
2 Reads

Evidence of batch effects masking treatment effect in GAW20 methylation data.

BMC Proc 2018 17;12(Suppl 9):32. Epub 2018 Sep 17.

2Genetics and Genome Biology Program, The Hospital for Sick Children Research Institute, 686 Bay St., Toronto, ON M5G 0A4 Canada.

Using the real data set from GAW20, we examined changes in the distribution of DNA methylation before and after treatment. Paired analysis of differences in both mean and variance had grossly inflated type 1 error, suggesting either a very large number of changes across the entire epigenome or major non-biological issues, such as batch effects. Separate analysis of Infinium I and II probes indicated differences in the paired -test statistics between these two types of probes. Read More

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http://dx.doi.org/10.1186/s12919-018-0129-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157182PMC
September 2018
1 Read

A Bayesian mixed modeling approach for estimating heritability.

BMC Proc 2018 17;12(Suppl 9):31. Epub 2018 Sep 17.

4Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Klaus Torgårds vei 3, 0372 Oslo, Norway.

Background: A 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 ( ), which are currently not well understood, as well as of blood lipid measurements.

Methods: We included individuals from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study with Infinium 450 K cytosine-phosphate-guanine (CpG) methylation and blood lipid data pre- and posttreatment with fenofibrate in families with up to three-generation pedigrees. Read More

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http://dx.doi.org/10.1186/s12919-018-0131-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157283PMC
September 2018
18 Reads

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

BMC Proc 2018 17;12(Suppl 9):28. Epub 2018 Sep 17.

2National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, 73 Mount Wayte Avenue, Framingham, MA 01702 USA.

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. Read More

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http://dx.doi.org/10.1186/s12919-018-0125-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157127PMC
September 2018
11 Reads

Network analysis of drug effect on triglyceride-associated DNA methylation.

BMC Proc 2018 17;12(Suppl 9):27. Epub 2018 Sep 17.

1Department of Biostatistics, Boston University, 801 Massachusetts Avenue 3rd Floor, Boston, MA 02118 USA.

Background: DNA methylation, an epigenetic modification, can be affected by environmental factors and thus regulate gene expression levels that can lead to alterations of certain phenotypes. Network analysis has been used successfully to discover gene sets that are expressed differently across multiple disease states and suggest possible pathways of disease progression. We applied this framework to compare DNA methylation levels before and after lipid-lowering medication and to identify modules that differ topologically between the two time points, revealing the association between lipid medication and these triglyceride-related methylation sites. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
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http://dx.doi.org/10.1186/s12919-018-0130-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157190PMC
September 2018
10 Reads

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

BMC Proc 2018 17;12(Suppl 9):25. Epub 2018 Sep 17.

Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4523 Clayton Ave, Saint Louis, MO 63110 USA.

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 subjects, but using a new fictitious drug (called "genomethate") that has a pharmaco-epigenetic effect on triglyceride response. For each replication, the pre-genomethate values at visits 1 and 2 are constant (ie, pedigree structures, age, sex, all phenotypes, covariates, genome-wide association study (GWAS) genotypes, and visit 2 methylation values), the same as the real GOLDN data across all 200 replications. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
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http://dx.doi.org/10.1186/s12919-018-0115-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157129PMC
September 2018
4 Reads

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

BMC Proc 2018 17;12(Suppl 9):23. Epub 2018 Sep 17.

5Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, 1665 University Blvd, Birmingham, AL USA.

Background: DNA 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 causality of the observed association remains elusive, hampered by weak instrumental variables for methylation status. Read More

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http://dx.doi.org/10.1186/s12919-018-0119-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157243PMC
September 2018
2 Reads

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

BMC Proc 2018 17;12(Suppl 9):22. Epub 2018 Sep 17.

1Department of Epidemiology, University of North Carolina, Chapel Hill, NC USA.

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 the causal genes and biochemical pathways that are involved in lipoprotein metabolism. However, methods for simultaneously analyzing multiple omics, environmental exposures, and longitudinally measured, correlated phenotypes are lacking. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
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http://dx.doi.org/10.1186/s12919-018-0118-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157130PMC
September 2018
4 Reads

Investigating potential causal relationships between SNPs, DNA methylation and HDL.

BMC Proc 2018 17;12(Suppl 9):20. Epub 2018 Sep 17.

1Department of Epidemiology, Biostatistics and Occupational Health, McGill University, 1020 Pine Avenue West, Quebec, Montreal H3A 1A2 Canada.

Using data on 680 patients from the GAW20 real data set, we conducted Mendelian randomization (MR) studies to explore the causal relationships between methylation levels at selected probes (cytosine-phosphate-guanine sites [CpGs]) and high-density lipoprotein (HDL) changes (Δ) using single-nucleotide polymorphisms (SNPs) as instrumental variables. Several methods were used to estimate the causal effects at CpGs of interest on Δ, including a newly developed method that we call (CIV). CIV performs automatic SNP selection while providing estimates of causal effects adjusted for possible pleiotropy, when the potentially-pleiotropic phenotypes are measured. Read More

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http://dx.doi.org/10.1186/s12919-018-0117-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157157PMC
September 2018
20 Reads

Application of Bayesian networks to GAW20 genetic and blood lipid data.

BMC Proc 2018 17;12(Suppl 9):19. Epub 2018 Sep 17.

Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ UK.

Background: Bayesian networks have been proposed as a way to identify possible causal relationships between measured variables based on their conditional dependencies and independencies. We explored the use of Bayesian network analyses applied to the GAW20 data to identify possible causal relationships between differential methylation of cytosine-phosphate-guanine dinucleotides (CpGs), single-nucleotide polymorphisms (SNPs), and blood lipid trait (triglycerides [TGs]).

Methods: After initial exploratory linear regression analyses, 2 Bayesian networks analyses were performed. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
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http://dx.doi.org/10.1186/s12919-018-0116-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157285PMC
September 2018
4 Reads

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

BMC Proc 2018 17;12(Suppl 9):57. Epub 2018 Sep 17.

1Lunenfeld-Tanenbaum Research Institute, Sinai Health System, 600 University Ave, Toronto, ON M5G 1X5 Canada.

Background: There 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.

Methods: We analyze chromosome 11 cytosine-phosphate-guanine (CpG) methylation levels and single-nucleotide polymorphism (SNP) genotypes from the original Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, aiming to explore the association between triglyceride levels and genetic/epigenetic factors. Read More

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http://dx.doi.org/10.1186/s12919-018-0142-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157034PMC
September 2018
9 Reads

Genome-wide association study for multiple phenotype analysis.

BMC Proc 2018 17;12(Suppl 9):55. Epub 2018 Sep 17.

Department of Biostatistics, School of Public Health, Boston University, 801 Massachusetts Avenue 3rd Floor, Boston, MA 02118 USA.

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 approaches to analyze multiple traits in GAW20 real samples, and compare the results. Read More

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http://dx.doi.org/10.1186/s12919-018-0135-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156845PMC
September 2018
7 Reads

Logistic Bayesian LASSO for detecting association combining family and case-control data.

BMC Proc 2018 17;12(Suppl 9):54. Epub 2018 Sep 17.

1Department of Statistics, The Ohio State University, 1958 Neil Avenue, Columbus, OH 43210 USA.

Because of the limited information from the GAW20 samples when only case-control or trio data are considered, we propose eLBL, an extension of the Logistic Bayesian LASSO (least absolute shrinkage and selection operator) methodology so that both types of data can be analyzed jointly in the hope of obtaining an increased statistical power, especially for detecting association between rare haplotypes and complex diseases. The methodology is further extended to account for familial correlation among the case-control individuals and the trios. A 2-step analysis strategy was taken to first perform a genome-wise single single-nucleotide polymorphism (SNP) search using the Monte Carlo pedigree disequilibrium test (MCPDT) to determine interesting regions for the Adult Treatment Panel (ATP) binary trait. Read More

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http://dx.doi.org/10.1186/s12919-018-0139-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156907PMC
September 2018
19 Reads

Gene-methylation epistatic analyses via the W-test identifies enriched signals of neuronal genes in patients undergoing lipid-control treatment.

BMC Proc 2018 17;12(Suppl 9):53. Epub 2018 Sep 17.

Division of Biostatistics, Centre for Clinical Research and Biostatistics, JC School of Public Health and Primary Care, the Chinese University of Hong Kong, Shatin, N.T., Hong Kong, Hong Kong, Special Administrative Region of China.

An increasing number of studies are focused on the epigenetic regulation of DNA to affect gene expression without modifications to the DNA sequence. Methylation plays an important role in shaping disease traits; however, previous studies were mainly experiment, based, resulting in few reports that measured gene-methylation interaction effects via statistical means. In this study, we applied the data set adaptive W-test to measure gene-methylation interactions. Read More

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http://dx.doi.org/10.1186/s12919-018-0143-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156903PMC
September 2018
3 Reads

Methods to evaluate rare variants gene-age interaction for triglycerides.

BMC Proc 2018 17;12(Suppl 9):49. Epub 2018 Sep 17.

2Department of Mathematics, University of North Texas, 1155 Union Circle #311430, Denton, TX 76203 USA.

Triglycerides are an important measure of heart health. Although more than 90 genes have been found to be associated to lipids, they only explain 12 to 15% of the variance in lipid levels. Evidence suggests that age may interact with the genetic effect on lipid levels. Read More

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http://dx.doi.org/10.1186/s12919-018-0136-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156913PMC
September 2018
15 Reads

Assessment of fenofibrate-methylation interactions on triglycerides using longitudinal family data.

BMC Proc 2018 17;12(Suppl 9):48. Epub 2018 Sep 17.

1Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, 35053 Taiwan.

Background: Triglyceride (TG) concentrations decrease in response to fenofibrate treatment, and also are associated with DNA methylation. But how interactions between fenofibrate response and DNA methylation affect TGs remains unclear.

Methods: In the present study, we identified and compared differential methylation sites associated with TG concentrations in individuals before and after fenofibrate treatment. Read More

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http://dx.doi.org/10.1186/s12919-018-0132-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156834PMC
September 2018
19 Reads

Homozygosity disequilibrium associated with treatment response and its methylation regulation.

BMC Proc 2018 17;12(Suppl 9):45. Epub 2018 Sep 17.

Institute of Statistical Science, Academia Sinica, No 128, Sec 2, Academia Rd, Nankang 115, Taipei, Taiwan.

Homozygosity disequilibrium (HD), indicating a nonrandom pattern of sizable runs of homozygosity that deviates from a random allocation of homozygous and heterozygous genotypes in the genome, is an important phenomenon in population genomics and medical genomics. We performed the first genome-wide study investigating the roles of HD in pharmacogenomics and pharmacoepigenomics by analyzing GAW20 data. We inferred whole-genome profiles of homozygosity intensities and performed genome-wide homozygosity association analyses to identify regions of HD associated with triglyceride (TG) response to fenofibrate by using LOHAS (Loss-of-Heterozygosity Analysis Suite) software. Read More

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http://dx.doi.org/10.1186/s12919-018-0150-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156896PMC
September 2018
12 Reads

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

BMC Proc 2018 17;12(Suppl 9):42. Epub 2018 Sep 17.

Department of Statistics, Columbia University, 1255 Amsterdam Avenue, New York, NY 10027 USA.

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. Read More

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http://dx.doi.org/10.1186/s12919-018-0151-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156900PMC
September 2018
1 Read

Methods for detecting methylation by SNP interaction in GAW20 simulation.

BMC Proc 2018 17;12(Suppl 9):37. Epub 2018 Sep 17.

Division of Statistical Genomics, Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 660 Euclid Ave., Saint Louis, MO 63110 USA.

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 interactions for SNP/CpG pairs were included. Causative SNPs/CpG pairs distributed on autosomal chromosomes 1 to 20 were tested to examine sensitivity. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
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http://dx.doi.org/10.1186/s12919-018-0140-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156982PMC
September 2018
9 Reads

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

BMC Proc 2018 17;12(Suppl 9):34. Epub 2018 Sep 17.

1South Texas Diabetes and Obesity Institute, Department of Human Genetics, University of Texas Rio Grande Valley School of Medicine, One University Blvd., Modular Building #100, Brownsville, TX 78250 USA.

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. Read More

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http://dx.doi.org/10.1186/s12919-018-0133-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157025PMC
September 2018
2 Reads

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

BMC Proc 2018 17;12(Suppl 9):30. Epub 2018 Sep 17.

3Department of Mathematics, Université du Québec à Montréal, 201, Ave. President Kennedy, Montreal, Montreal, H2X 3Y7 Canada.

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 taking into account correlations between DNA methylation at neighboring cytosine-phosphate-guanine (CpG) sites. To this end, we applied both a recently developed block-based data-dimension-reduction approach and a region-based variance-component (VC) linear mixed model to GAW20 data. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
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http://dx.doi.org/10.1186/s12919-018-0127-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157033PMC
September 2018
4 Reads

Modeling methylation data as an additional genetic variance component.

BMC Proc 2018 17;12(Suppl 9):29. Epub 2018 Sep 17.

1South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, One West University Blvd., STDOI Modular Building #100, Brownsville, TX 78520 USA.

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 methylation status of those sites. Read More

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http://dx.doi.org/10.1186/s12919-018-0128-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157027PMC
September 2018
17 Reads

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

BMC Proc 2018 17;12(Suppl 9):26. Epub 2018 Sep 17.

12Department of Genetics, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd., Philadelphia, PA 19104 USA.

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 Diet Network (GOLDN) investigators, included data from 188 families ( = 1105) which included genome-wide DNA methylation data before and after a 3-week treatment with fenofibrate, single-nucleotide polymorphisms, metabolic syndrome components before and after treatment, and a variety of covariates. Read More

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https://bmcproc.biomedcentral.com/articles/10.1186/s12919-01
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http://dx.doi.org/10.1186/s12919-018-0113-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156831PMC
September 2018
6 Reads

Joint screening of ultrahigh dimensional variables for family-based genetic studies.

BMC Proc 2018 17;12(Suppl 9):24. Epub 2018 Sep 17.

Department of Mathematical Sciences, New Jersey Institute of Technology, 323 Dr. Martin Luther King Jr. Blvd, Newark, NJ 07102 USA.

Background: Mixed models are a useful tool for evaluating the association between an outcome variable and genetic variables from a family-based genetic study, taking into account the kinship coefficients. When there are ultrahigh dimensional genetic variables (ie,  ≫ ), it is challenging to fit any mixed effect model.

Methods: We propose a two-stage strategy, screening genetic variables in the first stage and then fitting the mixed effect model in the second stage to those variables that survive the screening. Read More

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http://dx.doi.org/10.1186/s12919-018-0120-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156922PMC
September 2018
1 Read

A deep neural network based regression model for triglyceride concentrations prediction using epigenome-wide DNA methylation profiles.

BMC Proc 2018 17;12(Suppl 9):21. Epub 2018 Sep 17.

1Department of Biochemistry and Medical Genetics, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, MB R3E 0J9 Canada.

Background: Epigenetic modification has an effect on gene expression under the environmental alteration, but it does not change corresponding genome sequence. DNA methylation (DNAm) is one of the important epigenetic mechanisms. DNAm variations could be used as epigenetic markers to predict and account for the change of many human phenotypic traits, such as cancer, diabetes, and high blood pressure. Read More

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http://dx.doi.org/10.1186/s12919-018-0121-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157031PMC
September 2018
3 Reads

GM insect pests under the Brazilian regulatory framework: development and perspectives.

BMC Proc 2018 19;12(Suppl 8):16. Epub 2018 Jul 19.

3Instituto Agronômico de Pernambuco -IPA, Recife, PE Brazil.

The emergence of new technologies for genetic modification has broadened the range of possible new products. The regulations of many countries that could benefit from these new products may not be prepared to assess risks and enable science-based decision-making. This is especially acute in the case of genetically modified insects with potential use in public health and agriculture. Read More

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http://dx.doi.org/10.1186/s12919-018-0107-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069510PMC
July 2018
2 Reads

Towards inclusive social appraisal: risk, participation and democracy in governance of synthetic biology.

BMC Proc 2018 19;12(Suppl 8):15. Epub 2018 Jul 19.

3Department of Forestry and Environmental Resources, North Carolina State University, 2820 Faucette Dr, Raleigh, NC 27695 USA.

Frameworks that govern the development and application of novel products, such as the products of synthetic biology, should involve all those who are interested or potentially affected by the products. The governance arrangements for novel products should also provide a democratic mechanism that allows affected parties to express their opinions on the direction that innovation does or does not take. In this paper we examine rationales, obstacles and opportunities for public participation in governance of novel synthetic biology products. Read More

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http://dx.doi.org/10.1186/s12919-018-0111-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069769PMC
July 2018
2 Reads