Issue Information
(Source: Genetic Epidemiology)
Source: Genetic Epidemiology - November 19, 2017 Category: Epidemiology Tags: ISSUE INFORMATION Source Type: research
Integrative sparse principal component analysis of gene expression data
In this study, we conduct integrative analysis by developing the iSPCA (integrative SPCA) method. iSPCA achieves the selection and estimation of sparse loadings using a group penalty. To take advantage of the similarity across datasets and generate more accurate results, we further impose contrasted penalties. Different penalties are proposed to accommodate different data conditions. Extensive simulations show that iSPCA outperforms the alternatives under a wide spectrum of settings. The analysis of breast cancer and pancreatic cancer data further shows iSPCA's satisfactory performance. (Source: Genetic Epidemiology)
Source: Genetic Epidemiology - November 8, 2017 Category: Epidemiology Authors: Mengque Liu, Xinyan Fan, Kuangnan Fang, Qingzhao Zhang, Shuangge Ma Tags: RESEARCH ARTICLE Source Type: research
On meta ‐ and mega‐analyses for gene–environment interactions
ABSTRACT
Gene‐by‐environment (G × E) interactions are important in explaining the missing heritability and understanding the causation of complex diseases, but a single, moderately sized study often has limited statistical power to detect such interactions. With the increasing need for integrating data and reporting results from multiple collaborative studies or sites, debate over choice between mega‐ versus meta‐analysis continues. In principle, data from different sites can be integrated at the individual level into a “mega” data set, which can be fit by a joint “mega‐analysis.” Alternatively, analyses...
Source: Genetic Epidemiology - November 7, 2017 Category: Epidemiology Authors: Jing Huang, Yulun Liu, Steve Vitale, Trevor M. Penning, Alexander S. Whitehead, Ian A. Blair, Anil Vachani, Margie L. Clapper, Joshua E. Muscat, Philip Lazarus, Paul Scheet, Jason H. Moore, Yong Chen Tags: RESEARCH ARTICLE Source Type: research
Identification of 16q21 as a modifier of nonsyndromic orofacial cleft phenotypes
ABSTRACT
Orofacial clefts (OFCs) are common, complex birth defects with extremely heterogeneous phenotypic presentations. Two common subtypes—cleft lip alone (CL) and CL plus cleft palate (CLP)—are typically grouped into a single phenotype for genetic analysis (i.e., CL with or without cleft palate, CL/P). However, mounting evidence suggests there may be unique underlying pathophysiology and/or genetic modifiers influencing expression of these two phenotypes. To this end, we performed a genome‐wide scan for genetic modifiers by directly comparing 450 CL cases with 1,692 CLP cases from 18 recruitment sites across 13 c...
Source: Genetic Epidemiology - November 1, 2017 Category: Epidemiology Authors: Jenna C. Carlson, Jennifer Standley, Aline Petrin, John R. Shaffer, Azeez Butali, Carmen J. Bux ó, Eduardo Castilla, Kaare Christensen, Frederic W.‐D. Deleyiannis, Jacqueline T. Hecht, L. Leigh Field, Ariuntuul Garidkhuu, Lina M. Moreno Uribe, Natsume Tags: RESEARCH ARTICLE Source Type: research
An integrative approach to assess X ‐chromosome inactivation using allele‐specific expression with applications to epithelial ovarian cancer
ABSTRACT
X‐chromosome inactivation (XCI) epigenetically silences transcription of an X chromosome in females; patterns of XCI are thought to be aberrant in women's cancers, but are understudied due to statistical challenges. We develop a two‐stage statistical framework to assess skewed XCI and evaluate gene‐level patterns of XCI for an individual sample by integration of RNA sequence, copy number alteration, and genotype data. Our method relies on allele‐specific expression (ASE) to directly measure XCI and does not rely on male samples or paired normal tissue for comparison. We model ASE using a two‐component mi...
Source: Genetic Epidemiology - November 1, 2017 Category: Epidemiology Authors: Nicholas B. Larson, Zachary C. Fogarty, Melissa C. Larson, Kimberly R. Kalli, Kate Lawrenson, Simon Gayther, Brooke L. Fridley, Ellen L. Goode, Stacey J. Winham Tags: RESEARCH ARTICLE Source Type: research
An ancestry ‐based approach for detecting interactions
ConclusionWe show that genetic ancestry can be a useful proxy for unknown and unmeasured covariates in the search for interaction effects. These results have important implications for our understanding of the genetic architecture of complex traits. (Source: Genetic Epidemiology)
Source: Genetic Epidemiology - November 1, 2017 Category: Epidemiology Authors: Danny S. Park, Itamar Eskin, Eun Yong Kang, Eric R. Gamazon, Celeste Eng, Christopher R. Gignoux, Joshua M. Galanter, Esteban Burchard, Chun J. Ye, Hugues Aschard, Eleazar Eskin, Eran Halperin, Noah Zaitlen Tags: RESEARCH ARTICLE Source Type: research
Multiethnic polygenic risk scores improve risk prediction in diverse populations
ABSTRACT
Methods for genetic risk prediction have been widely investigated in recent years. However, most available training data involves European samples, and it is currently unclear how to accurately predict disease risk in other populations. Previous studies have used either training data from European samples in large sample size or training data from the target population in small sample size, but not both. Here, we introduce a multiethnic polygenic risk score that combines training data from European samples and training data from the target population. We applied this approach to predict type 2 diabetes (T2D) in a ...
Source: Genetic Epidemiology - November 1, 2017 Category: Epidemiology Authors: Carla M árquez‐Luna, Po‐Ru Loh, , , Alkes L. Price Tags: RESEARCH ARTICLE Source Type: research
Testing for the indirect effect under the null for genome ‐wide mediation analyses
We examined the performance of commonly used mediation testing methods for the indirect effect in genome‐wide mediation studies. When there is no association between the exposure and the mediator and no association between the mediator and the outcome, we show that these common tests are overly conservative. This is a case that will arise frequently in genome‐wide mediation studies. Caution is hence needed when applying the commonly used mediation tests in genome‐wide mediation studies. We evaluated the performance of these methods using simulation studies, and performed an epigenome‐wide mediation association stud...
Source: Genetic Epidemiology - October 30, 2017 Category: Epidemiology Authors: Richard Barfield, Jincheng Shen, Allan C. Just, Pantel S. Vokonas, Joel Schwartz, Andrea A. Baccarelli, Tyler J. VanderWeele, Xihong Lin Tags: RESEARCH ARTICLE Source Type: research
Rare ‐variant association tests in longitudinal studies, with an application to the Multi‐Ethnic Study of Atherosclerosis (MESA)
Abstract
Over the past few years, an increasing number of studies have identified rare variants that contribute to trait heritability. Due to the extreme rarity of some individual variants, gene‐based association tests have been proposed to aggregate the genetic variants within a gene, pathway, or specific genomic region as opposed to a one‐at‐a‐time single variant analysis. In addition, in longitudinal studies, statistical power to detect disease susceptibility rare variants can be improved through jointly testing repeatedly measured outcomes, which better describes the temporal development of the trait of interes...
Source: Genetic Epidemiology - October 27, 2017 Category: Epidemiology Authors: Zihuai He, Seunggeun Lee, Min Zhang, Jennifer A. Smith, Xiuqing Guo, Walter Palmas, Sharon L.R. Kardia, Iuliana Ionita ‐Laza, Bhramar Mukherjee Tags: RESEARCH ARTICLE Source Type: research
On the testing of Hardy ‐Weinberg proportions and equality of allele frequencies in males and females at biallelic genetic markers
ABSTRACT
Standard statistical tests for equality of allele frequencies in males and females and tests for Hardy‐Weinberg equilibrium are tightly linked by their assumptions. Tests for equality of allele frequencies assume Hardy‐Weinberg equilibrium, whereas the usual chi‐square or exact test for Hardy‐Weinberg equilibrium assume equality of allele frequencies in the sexes. In this paper, we propose ways to break this interdependence in assumptions of the two tests by proposing an omnibus exact test that can test both hypotheses jointly, as well as a likelihood ratio approach that permits these phenomena to be teste...
Source: Genetic Epidemiology - October 26, 2017 Category: Epidemiology Authors: Jan Graffelman, Bruce S. Weir Tags: RESEARCH ARTICLE Source Type: research
Impact of sample collection participation on the validity of estimated measures of association in the National Birth Defects Prevention Study when assessing gene ‐environment interactions
Abstract
To better understand the impact that nonresponse for specimen collection has on the validity of estimates of association, we examined associations between self‐reported maternal periconceptional smoking, folic acid use, or pregestational diabetes mellitus and six birth defects among families who did and did not submit buccal cell samples for DNA following a telephone interview as part of the National Birth Defects Prevention Study (NBDPS). Analyses included control families with live born infants who had no birth defects (N = 9,465), families of infants with anorectal atresia or stenosis (N = 873), limb reductio...
Source: Genetic Epidemiology - October 25, 2017 Category: Epidemiology Authors: Mary M. Jenkins, Jennita Reefhuis, Amy H. Herring, Margaret A. Honein Tags: RESEARCH ARTICLE Source Type: research
Estimation of a significance threshold for epigenome ‐wide association studies
ABSTRACT
Epigenome‐wide association studies (EWAS) are designed to characterise population‐level epigenetic differences across the genome and link them to disease. Most commonly, they assess DNA‐methylation status at cytosine‐guanine dinucleotide (CpG) sites, using platforms such as the Illumina 450k array that profile a subset of CpGs genome wide. An important challenge in the context of EWAS is determining a significance threshold for declaring a CpG site as differentially methylated, taking multiple testing into account. We used a permutation method to estimate a significance threshold specifically for the 450k ...
Source: Genetic Epidemiology - October 16, 2017 Category: Epidemiology Authors: Ayden Saffari, Matt J. Silver, Patrizia Zavattari, Loredana Moi, Amedeo Columbano, Emma L. Meaburn, Frank Dudbridge Tags: RESEARCH ARTICLE Source Type: research
Corrigendum
(Source: Genetic Epidemiology)
Source: Genetic Epidemiology - October 16, 2017 Category: Epidemiology Tags: CORRIGENDUM Source Type: research
Issue Information
(Source: Genetic Epidemiology)
Source: Genetic Epidemiology - October 16, 2017 Category: Epidemiology Tags: ISSUE INFORMATION Source Type: research
Mendelian randomization with fine ‐mapped genetic data: Choosing from large numbers of correlated instrumental variables
ABSTRACT
Mendelian randomization uses genetic variants to make causal inferences about the effect of a risk factor on an outcome. With fine‐mapped genetic data, there may be hundreds of genetic variants in a single gene region any of which could be used to assess this causal relationship. However, using too many genetic variants in the analysis can lead to spurious estimates and inflated Type 1 error rates. But if only a few genetic variants are used, then the majority of the data is ignored and estimates are highly sensitive to the particular choice of variants. We propose an approach based on summarized data only (gene...
Source: Genetic Epidemiology - September 25, 2017 Category: Epidemiology Authors: Stephen Burgess, Verena Zuber, Elsa Valdes ‐Marquez, Benjamin B Sun, Jemma C Hopewell Tags: RESEARCH ARTICLE Source Type: research
