Evidence for SNP ‐SNP interaction identified through targeted sequencing of cleft case‐parent trios
ABSTRACT
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans, affecting 1 in 700 live births. This malformation has a complex etiology where multiple genes and several environmental factors influence risk. At least a dozen different genes have been confirmed to be associated with risk of NSCL/P in previous studies. However, all the known genetic risk factors cannot fully explain the observed heritability of NSCL/P, and several authors have suggested gene‐gene (G × G) interaction may be important in the etiology of this complex and heterogeneous malformation...
Source: Genetic Epidemiology - December 26, 2016 Category: Epidemiology Authors: Yanzi Xiao, Margaret A. Taub, Ingo Ruczinski, Ferdouse Begum, Jacqueline B. Hetmanski, Holger Schwender, Elizabeth J. Leslie, Daniel C. Koboldt, Jeffrey C. Murray, Mary L. Marazita, Terri H. Beaty Tags: Research Article Source Type: research
Impact of genotyping errors on statistical power of association tests in genomic analyses: A case study
ABSTRACT
A key step in genomic studies is to assess high throughput measurements across millions of markers for each participant's DNA, either using microarrays or sequencing techniques. Accurate genotype calling is essential for downstream statistical analysis of genotype‐phenotype associations, and next generation sequencing (NGS) has recently become a more common approach in genomic studies. How the accuracy of variant calling in NGS‐based studies affects downstream association analysis has not, however, been studied using empirical data in which both microarrays and NGS were available. In this article, we investiga...
Source: Genetic Epidemiology - December 25, 2016 Category: Epidemiology Authors: Lin Hou, Ning Sun, Shrikant Mane, Fred Sayward, Nallakkandi Rajeevan, Kei ‐Hoi Cheung, Kelly Cho, Saiju Pyarajan, Mihaela Aslan, Perry Miller, Philip D. Harvey, J. Michael Gaziano, John Concato, Hongyu Zhao Tags: Research Article Source Type: research
Integration of gene expression and methylation to unravel biological networks in glioblastoma patients
ABSTRACT
The vast amount of heterogeneous omics data, encompassing a broad range of biomolecular information, requires novel methods of analysis, including those that integrate the available levels of information. In this work, we describe Regression2Net, a computational approach that is able to integrate gene expression and genomic or methylation data in two steps. First, penalized regressions are used to build Expression‐Expression (EEnet) and Expression‐Genomic or Expression‐Methylation (EMnet) networks. Second, network theory is used to highlight important communities of genes. When applying our approach, Regress...
Source: Genetic Epidemiology - December 25, 2016 Category: Epidemiology Authors: Francesco Gadaleta, Kyrylo Bessonov, Kristel Steen Tags: Research Article Source Type: research
A small ‐sample multivariate kernel machine test for microbiome association studies
ABSTRACT
High‐throughput sequencing technologies have enabled large‐scale studies of the role of the human microbiome in health conditions and diseases. Microbial community level association test, as a critical step to establish the connection between overall microbiome composition and an outcome of interest, has now been routinely performed in many studies. However, current microbiome association tests all focus on a single outcome. It has become increasingly common for a microbiome study to collect multiple, possibly related, outcomes to maximize the power of discovery. As these outcomes may share common mechanisms, ...
Source: Genetic Epidemiology - December 25, 2016 Category: Epidemiology Authors: Xiang Zhan, Xingwei Tong, Ni Zhao, Arnab Maity, Michael C. Wu, Jun Chen Tags: Research Article Source Type: research
Resetting the bar: Statistical significance in whole ‐genome sequencing‐based association studies of global populations
ABSTRACT
Genome‐wide association studies (GWAS) of common disease have been hugely successful in implicating loci that modify disease risk. The bulk of these associations have proven robust and reproducible, in part due to community adoption of statistical criteria for claiming significant genotype‐phenotype associations. As the cost of sequencing continues to drop, assembling large samples in global populations is becoming increasingly feasible. Sequencing studies interrogate not only common variants, as was true for genotyping‐based GWAS, but variation across the full allele frequency spectrum, yielding many more (...
Source: Genetic Epidemiology - December 19, 2016 Category: Epidemiology Authors: Sara L. Pulit, Sera A. J. With, Paul I. W. Bakker Tags: Research Article Source Type: research
Issue Information
(Source: Genetic Epidemiology)
Source: Genetic Epidemiology - December 12, 2016 Category: Epidemiology Tags: Issue Information Source Type: research
Leveraging population information in family ‐based rare variant association analyses of quantitative traits
ABSTRACT
Confounding due to population substructure is always a concern in genetic association studies. Although methods have been proposed to adjust for population stratification in the context of common variation, it is unclear how well these approaches will work when interrogating rare variation. Family‐based association tests can be constructed that are robust to population stratification. For example, when considering a quantitative trait, a linear model can be used that decomposes genetic effects into between‐ and within‐family components and a test of the within‐family component is robust to population strat...
Source: Genetic Epidemiology - December 4, 2016 Category: Epidemiology Authors: Yu Jiang, Yunqi Ji, Alexander B. Sibley, Yi ‐Ju Li, Andrew S. Allen Tags: Research Article Source Type: research
Genome ‐wide survey in African Americans demonstrates potential epistasis of fitness in the human genome
In this study, we developed a novel method to detect fitness epistasis by testing the correlation between local ancestries on different chromosomes in an admixed population. We inferred local ancestry across the genome in 16,252 unrelated African Americans and systematically examined the pairwise correlations between the genomic regions on different chromosomes. Our analysis revealed a pair of genomic regions on chromosomes 4 and 6 that show significant local ancestry correlation (P‐value = 4.01 × 10−8) that can be potentially attributed to fitness epistasis. However, we also observed substantial local ancestry correl...
Source: Genetic Epidemiology - December 4, 2016 Category: Epidemiology Authors: Heming Wang, Yoonha Choi, Bamidele Tayo, Xuefeng Wang, Nathan Morris, Xiang Zhang, Uli Broeckel, Craig Hanis, Sharon Kardia, Susan Redline, Richard S Cooper, Hua Tang, Xiaofeng Zhu Tags: Research Article Source Type: research
Fast Genome ‐Wide QTL Association Mapping on Pedigree and Population Data
ABSTRACT
Since most analysis software for genome‐wide association studies (GWAS) currently exploit only unrelated individuals, there is a need for efficient applications that can handle general pedigree data or mixtures of both population and pedigree data. Even datasets thought to consist of only unrelated individuals may include cryptic relationships that can lead to false positives if not discovered and controlled for. In addition, family designs possess compelling advantages. They are better equipped to detect rare variants, control for population stratification, and facilitate the study of parent‐of‐origin effec...
Source: Genetic Epidemiology - November 30, 2016 Category: Epidemiology Authors: Hua Zhou, John Blangero, Thomas D. Dyer, Kei ‐hang K. Chan, Kenneth Lange, Eric M. Sobel Tags: Research Article Source Type: research
A comparison study of multivariate fixed models and Gene Association with Multiple Traits (GAMuT) for next ‐generation sequencing
ABSTRACT
In this paper, extensive simulations are performed to compare two statistical methods to analyze multiple correlated quantitative phenotypes: (1) approximate F‐distributed tests of multivariate functional linear models (MFLM) and additive models of multivariate analysis of variance (MANOVA), and (2) Gene Association with Multiple Traits (GAMuT) for association testing of high‐dimensional genotype data. It is shown that approximate F‐distributed tests of MFLM and MANOVA have higher power and are more appropriate for major gene association analysis (i.e., scenarios in which some genetic variants have relativel...
Source: Genetic Epidemiology - November 30, 2016 Category: Epidemiology Authors: Chi ‐Yang Chiu, Jeesun Jung, Yifan Wang, Daniel E. Weeks, Alexander F. Wilson, Joan E. Bailey‐Wilson, Christopher I. Amos, James L. Mills, Michael Boehnke, Momiao Xiong, Ruzong Fan Tags: Research Article Source Type: research
A general approach to testing for pleiotropy with rare and common variants
ABSTRACT
Through genome‐wide association studies, numerous genes have been shown to be associated with multiple phenotypes. To determine the overlap of genetic susceptibility of correlated phenotypes, one can apply multivariate regression or dimension reduction techniques, such as principal components analysis, and test for the association with the principal components of the phenotypes rather than the individual phenotypes. However, as these approaches test whether there is a genetic effect for at least one of the phenotypes, a significant test result does not necessarily imply pleiotropy. Recently, a method called Plei...
Source: Genetic Epidemiology - November 30, 2016 Category: Epidemiology Authors: Sharon M. Lutz, Tasha E. Fingerlin, John E. Hokanson, Christoph Lange Tags: Research Article Source Type: research
Multiple linear combination (MLC) regression tests for common variants adapted to linkage disequilibrium structure
ABSTRACT
By jointly analyzing multiple variants within a gene, instead of one at a time, gene‐based multiple regression can improve power, robustness, and interpretation in genetic association analysis. We investigate multiple linear combination (MLC) test statistics for analysis of common variants under realistic trait models with linkage disequilibrium (LD) based on HapMap Asian haplotypes. MLC is a directional test that exploits LD structure in a gene to construct clusters of closely correlated variants recoded such that the majority of pairwise correlations are positive. It combines variant effects within the same cl...
Source: Genetic Epidemiology - November 25, 2016 Category: Epidemiology Authors: Yun Joo Yoo, Lei Sun, Julia G. Poirier, Andrew D. Paterson, Shelley B. Bull Tags: Research Article Source Type: research
Use of big data for drug development and for public and personal health and care
This article looks at the different sources of data and the importance of unstructured data. It goes on to summarize current and potential future uses in drug discovery, development, and monitoring as well as in public and personal healthcare; including examples of good practice and recent developments. Finally, we discuss the main practical and ethical challenges to unravel the full potential of big data in healthcare and conclude that all stakeholders need to work together towards the common goal of making sense of the available data for the common good. (Source: Genetic Epidemiology)
Source: Genetic Epidemiology - November 22, 2016 Category: Epidemiology Authors: Lada Leyens, Matthias Reumann, Nuria Malats, Angela Brand Tags: Research Article Source Type: research
A method for integrating neuroimaging into genetic models of learning performance
ABSTRACT
Specific learning disorders (SLD) are an archetypal example of how clinical neuropsychological (NP) traits can differ from underlying genetic and neurobiological risk factors. Disparate environmental influences and pathologies impact learning performance assessed through cognitive examinations and clinical evaluations, the primary diagnostic tools for SLD. We propose a neurobiological risk for SLD with neuroimaging biomarkers, which is integrated into a genome‐wide association study (GWAS) of learning performance in a cohort of 479 European individuals between 8 and 21 years of age. We first identified six regio...
Source: Genetic Epidemiology - November 18, 2016 Category: Epidemiology Authors: Chintan M. Mehta, Jeffrey R. Gruen, Heping Zhang Tags: Research Article Source Type: research
Issue Information
(Source: Genetic Epidemiology)
Source: Genetic Epidemiology - November 15, 2016 Category: Epidemiology Tags: Issue Information Source Type: research
