A Critical Look at Entropy‐Based Gene‐Gene Interaction Measures
ABSTRACT
Several entropy‐based measures for detecting gene‐gene interaction have been proposed recently. It has been argued that the entropy‐based measures are preferred because entropy can better capture the nonlinear relationships between genotypes and traits, so they can be useful to detect gene‐gene interactions for complex diseases. These suggested measures look reasonable at intuitive level, but so far there has been no detailed characterization of the interactions captured by them. Here we study analytically the properties of some entropy‐based measures for detecting gene‐gene interactions in detail. The...
Source: Genetic Epidemiology - May 26, 2016 Category: Epidemiology Authors: Woojoo Lee, Arvid Sjölander, Yudi Pawitan Tags: Research Article Source Type: research
G‐STRATEGY: Optimal Selection of Individuals for Sequencing in Genetic Association Studies
ABSTRACT
In a large‐scale genetic association study, the number of phenotyped individuals available for sequencing may, in some cases, be greater than the study's sequencing budget will allow. In that case, it can be important to prioritize individuals for sequencing in a way that optimizes power for association with the trait. Suppose a cohort of phenotyped individuals is available, with some subset of them possibly already sequenced, and one wants to choose an additional fixed‐size subset of individuals to sequence in such a way that the power to detect association is maximized. When the phenotyped sample includes re...
Source: Genetic Epidemiology - April 30, 2016 Category: Epidemiology Authors: Miaoyan Wang, Johanna Jakobsdottir, Albert V. Smith, Mary Sara McPeek Tags: Research Article Source Type: research
Analyzing Association Mapping in Pedigree‐Based GWAS Using a Penalized Multitrait Mixed Model
This study has been partly motivated by the analysis of Genetic Analysis Workshop (GAW) 18 data, which have two notable characteristics. First, the subjects are from a small number of pedigrees and hence related. Second, for each subject, multiple correlated traits have been measured. Most of the existing penalization methods assume independence between subjects and traits and can be suboptimal. There are a few methods in the literature based on mixed modeling that can accommodate correlations. However, they cannot fully accommodate the two types of correlations while conducting effective marker selection. In this study, w...
Source: Genetic Epidemiology - April 30, 2016 Category: Epidemiology Authors: Jin Liu, Can Yang, Xingjie Shi, Cong Li, Jian Huang, Hongyu Zhao, Shuangge Ma Tags: Research Article Source Type: research
Determining Which Phenotypes Underlie a Pleiotropic Signal
ABSTRACT
Discovering pleiotropic loci is important to understand the biological basis of seemingly distinct phenotypes. Most methods for assessing pleiotropy only test for the overall association between genetic variants and multiple phenotypes. To determine which specific traits are pleiotropic, we evaluate via simulation and application three different strategies. The first is model selection techniques based on the inverse regression of genotype on phenotypes. The second is a subset‐based meta analysis ASSET [Bhattacharjee et al., ], which provides an optimal subset of nonnull traits. And the third is a modified Benj...
Source: Genetic Epidemiology - April 30, 2016 Category: Epidemiology Authors: Arunabha Majumdar, Tanushree Haldar, John S. Witte Tags: Research Article Source Type: research
Using Whole Exome Sequencing to Identify Candidate Genes With Rare Variants In Nonsyndromic Cleft Lip and Palate
ABSTRACT
Studies suggest that nonsyndromic cleft lip and palate (NSCLP) is polygenic with variable penetrance, presenting a challenge in identifying all causal genetic variants. Despite relatively high prevalence of NSCLP among Amerindian populations, no large whole exome sequencing (WES) studies have been completed in this population. Our goal was to identify candidate genes with rare genetic variants for NSCLP in a Honduran population using WES. WES was performed on two to four members of 27 multiplex Honduran families. Genetic variants with a minor allele frequency > 1% in reference databases were removed. Heterozygo...
Source: Genetic Epidemiology - April 30, 2016 Category: Epidemiology Authors: Alana Aylward, Yi Cai, Andrew Lee, Elizabeth Blue, Daniel Rabinowitz, Joseph Haddad, Tags: Research Article Source Type: research
Penetrance of ATM Gene Mutations in Breast Cancer: A Meta‐Analysis of Different Measures of Risk
ABSTRACT
The gene responsible for ataxia‐telangiectasia syndrome, ATM, is also an intermediate‐risk breast cancer (BC) susceptibility gene. Numerous studies have been carried out to determine the contribution of ATM gene mutations to BC risk. Epidemiological cohorts, segregation analyses, and case‐control studies reported BC risk in different forms, including penetrance, relative risk, standardized incidence ratio, and odds ratio. Because the reported estimates vary both qualitatively and quantitatively, we developed a general model allowing the integration of the different types of cancer risk available in the liter...
Source: Genetic Epidemiology - April 26, 2016 Category: Epidemiology Authors: Monica Marabelli, Su‐Chun Cheng, Giovanni Parmigiani Tags: Research Article Source Type: research
Penetrance of ATM Gene Mutations in Breast Cancer: A Meta ‐Analysis of Different Measures of Risk
ABSTRACT
The gene responsible for ataxia‐telangiectasia syndrome, ATM, is also an intermediate‐risk breast cancer (BC) susceptibility gene. Numerous studies have been carried out to determine the contribution of ATM gene mutations to BC risk. Epidemiological cohorts, segregation analyses, and case‐control studies reported BC risk in different forms, including penetrance, relative risk, standardized incidence ratio, and odds ratio. Because the reported estimates vary both qualitatively and quantitatively, we developed a general model allowing the integration of the different types of cancer risk available in the liter...
Source: Genetic Epidemiology - April 24, 2016 Category: Epidemiology Authors: Monica Marabelli, Su ‐Chun Cheng, Giovanni Parmigiani Tags: Research Article Source Type: research
An Object‐Oriented Regression for Building Disease Predictive Models with Multiallelic HLA Genes
ABSTRACT
Recent genome‐wide association studies confirm that human leukocyte antigen (HLA) genes have the strongest associations with several autoimmune diseases, including type 1 diabetes (T1D), providing an impetus to reduce this genetic association to practice through an HLA‐based disease predictive model. However, conventional model‐building methods tend to be suboptimal when predictors are highly polymorphic with many rare alleles combined with complex patterns of sequence homology within and between genes. To circumvent this challenge, we describe an alternative methodology; treating complex genotypes of HLA g...
Source: Genetic Epidemiology - April 14, 2016 Category: Epidemiology Authors: Lue Ping Zhao, Hamid Bolouri, Michael Zhao, Daniel E. Geraghty, Åke Lernmark, Tags: Research Article Source Type: research
Issue Information
(Source: Genetic Epidemiology)
Source: Genetic Epidemiology - April 14, 2016 Category: Epidemiology Tags: Issue Information Source Type: research
Review of the Gene ‐Environment Interaction Literature in Cancer: What Do We Know?
ConclusionObservations of published literature suggest that opportunity exists for increased sample size in G×E research, including GWAS‐identified loci in G×E studies, exploring more GWAS approaches in G×E such as GEWIS, and improving the reporting of G×E findings. (Source: Genetic Epidemiology)
Source: Genetic Epidemiology - April 6, 2016 Category: Epidemiology Authors: Naoko I. Simonds, Armen A. Ghazarian, Camilla B. Pimentel, Sheri D. Schully, Gary L. Ellison, Elizabeth M. Gillanders, Leah E. Mechanic Tags: Review Article Source Type: research
Testing Allele Transmission of an SNP Set Using a Family‐Based Generalized Genetic Random Field Method
ABSTRACT
Family‐based association studies are commonly used in genetic research because they can be robust to population stratification (PS). Recent advances in high‐throughput genotyping technologies have produced a massive amount of genomic data in family‐based studies. However, current family‐based association tests are mainly focused on evaluating individual variants one at a time. In this article, we introduce a family‐based generalized genetic random field (FB‐GGRF) method to test the joint association between a set of autosomal SNPs (i.e., single‐nucleotide polymorphisms) and disease phenotypes. The pr...
Source: Genetic Epidemiology - April 6, 2016 Category: Epidemiology Authors: Ming Li, Jingyun Li, Zihuai He, Qing Lu, John S. Witte, Stewart L. Macleod, Charlotte A. Hobbs, Mario A. Cleves, Tags: Research Article Source Type: research
Across‐Platform Imputation of DNA Methylation Levels Incorporating Nonlocal Information Using Penalized Functional Regression
In this study, we propose a penalized functional regression model to impute missing methylation data. By incorporating functional predictors, our model utilizes information from nonlocal probes to improve imputation quality. Here, we compared the performance of our functional model to linear regression and the best single probe surrogate in real data and via simulations. Specifically, we applied different imputation approaches to an acute myeloid leukemia dataset consisting of 194 samples and our method showed higher imputation accuracy, manifested, for example, by a 94% relative increase in information content and up to 8...
Source: Genetic Epidemiology - April 6, 2016 Category: Epidemiology Authors: Guosheng Zhang, Kuan‐Chieh Huang, Zheng Xu, Jung‐Ying Tzeng, Karen N. Conneely, Weihua Guan, Jian Kang, Yun Li Tags: Research Article Source Type: research
Review of the Gene‐Environment Interaction Literature in Cancer: What Do We Know?
ConclusionObservations of published literature suggest that opportunity exists for increased sample size in G×E research, including GWAS‐identified loci in G×E studies, exploring more GWAS approaches in G×E such as GEWIS, and improving the reporting of G×E findings. (Source: Genetic Epidemiology)
Source: Genetic Epidemiology - April 6, 2016 Category: Epidemiology Authors: Naoko I. Simonds, Armen A. Ghazarian, Camilla B. Pimentel, Sheri D. Schully, Gary L. Ellison, Elizabeth M. Gillanders, Leah E. Mechanic Tags: Review Article Source Type: research
Polygenic Epidemiology
ABSTRACT
Much of the genetic basis of complex traits is present on current genotyping products, but the individual variants that affect the traits have largely not been identified. Several traditional problems in genetic epidemiology have recently been addressed by assuming a polygenic basis for disease and treating it as a single entity. Here I briefly review some of these applications, which collectively may be termed polygenic epidemiology. Methodologies in this area include polygenic scoring, linear mixed models, and linkage disequilibrium scoring. They have been used to establish a polygenic effect, estimate genetic c...
Source: Genetic Epidemiology - April 6, 2016 Category: Epidemiology Authors: Frank Dudbridge Tags: Review Article Source Type: research
Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator
We present a novel weighted median estimator for combining data on multiple genetic variants into a single causal estimate. This estimator is consistent even when up to 50% of the information comes from invalid instrumental variables. In a simulation analysis, it is shown to have better finite‐sample Type 1 error rates than the inverse‐variance weighted method, and is complementary to the recently proposed MR‐Egger (Mendelian randomization‐Egger) regression method. In analyses of the causal effects of low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol on coronary artery disease risk, t...
Source: Genetic Epidemiology - April 6, 2016 Category: Epidemiology Authors: Jack Bowden, George Davey Smith, Philip C. Haycock, Stephen Burgess Tags: Research Article Source Type: research
