Regionally Smoothed Meta-Analysis Methods for GWAS Datasets.

Abstract:

:Genome-wide association studies are proven tools for finding disease genes, but it is often necessary to combine many cohorts into a meta-analysis to detect statistically significant genetic effects. Often the component studies are performed by different investigators on different populations, using different chips with minimal SNPs overlap. In some cases, raw data are not available for imputation so that only the genotyped single nucleotide polymorphisms (SNPs) results can be used in meta-analysis. Even when SNP sets are comparable, different cohorts may have peak association signals at different SNPs within the same gene due to population differences in linkage disequilibrium or environmental interactions. We hypothesize that the power to detect statistical signals in these situations will improve by using a method that simultaneously meta-analyzes and smooths the signal over nearby markers. In this study, we propose regionally smoothed meta-analysis methods and compare their performance on real and simulated data.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

authors

Begum F,Sharker MH,Sherman SL,Tseng GC,Feingold E

doi

10.1002/gepi.21949

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

154-60

issue

2

eissn

0741-0395

issn

1098-2272

journal_volume

40

pub_type

杂志文章
  • Gene-environment interaction tests for dichotomous traits in trios and sibships.

    abstract::When testing for genetic effects, failure to account for a gene-environment interaction can mask the true association effects of a genetic marker with disease. Family-based association tests are popular because they are completely robust to population substructure and model misspecification. However, when testing for ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20421

    authors: Hoffmann TJ,Lange C,Vansteelandt S,Laird NM

    更新日期:2009-12-01 00:00:00

  • On the detection of linkage in multiple data sets: a comparison of various statistical approaches.

    abstract::We contrast the pooling of multiple data sets with the compound HLOD (HLOD-C) and the posterior probability of linkage (PPL), two approaches that have been shown to have more power in the presence of genetic heterogeneity. We also propose and evaluate several multipoint extensions. ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.2001.21.s1.s67

    authors: Van Eerdewegh P,Dowd M,Dupuis J,Falls K,Hayward B,Santangelo SL

    更新日期:2001-01-01 00:00:00

  • Measuring the inflation of the lod score due to its maximization over model parameter values in human linkage analysis.

    abstract::A computer-simulation method is presented for determining and correcting for the effect of maximizing the lod score over disease definitions, penetrance values, and perhaps other model parameters. The method consists of simulating the complete analysis using marker genotypes randomly generated under the assumption of ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370070402

    authors: Weeks DE,Lehner T,Squires-Wheeler E,Kaufmann C,Ott J

    更新日期:1990-01-01 00:00:00

  • Heritability analysis of nontraditional glycemic biomarkers in the Atherosclerosis Risk in Communities Study.

    abstract::Nontraditional glycemic biomarkers, including fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG) are potential alternatives or complement to traditional measures of hyperglycemia. Genetic variants are associated with these biomarkers, but the heritability, or extent to which genetics control their variat...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22243

    authors: Loomis SJ,Tin A,Coresh J,Boerwinkle E,Pankow JS,Köttgen A,Selvin E,Duggal P

    更新日期:2019-10-01 00:00:00

  • Genetic prediction in the Genetic Analysis Workshop 18 sequencing data.

    abstract::High-throughput sequencing data can be used to predict phenotypes from genotypes, and this corresponds to establishing a prognostic model. In extended pedigrees the relatedness of subjects provides additional information so that genetic values, fixed or random genetic components, and heritability can be estimated. At ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21826

    authors: Ziegler A,Bohossian N,Diego VP,Yao C

    更新日期:2014-09-01 00:00:00

  • Genome-wide detection and characterization of mating asymmetry in human populations.

    abstract::The study of the genetic component of early-onset diseases requires investigation into parental genetic effects, particularly those mediated by the mother who can influence the offspring's risk of disease through the effects of her genes acting directly on the intrauterine milieu or indirectly through maternal-gene ch...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20602

    authors: Bourgey M,Healy J,Saint-Onge P,Massé H,Sinnett D,Roy-Gagnon MH

    更新日期:2011-09-01 00:00:00

  • Improving power in genome-wide association studies: weights tip the scale.

    abstract::The potential of genome-wide association analysis can only be realized when they have power to detect signals despite the detrimental effect of multiple testing on power. We develop a weighted multiple testing procedure that facilitates the input of prior information in the form of groupings of tests. For each group a...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20237

    authors: Roeder K,Devlin B,Wasserman L

    更新日期:2007-11-01 00:00:00

  • Scope and strategies of genetic epidemiology: analysis of articles published in Genetic Epidemiology, 1984-1991.

    abstract::Genetic epidemiology is a relatively new discipline that seeks to unravel the role of genetic factors and their interactions with environmental factors in the etiology of diseases, using population and family study approaches. To characterize the overall direction and emphasis of research strategies used in this field...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370100505

    authors: Khoury MJ,Beaty TH,Cohen BH

    更新日期:1993-01-01 00:00:00

  • Genetic association tests based on ranks (GATOR) for quantitative traits with and without censoring.

    abstract::Linkage disequilibrium mapping of quantitative traits is a powerful method for dissecting the genetic etiology of complex phenotypes. Quantitative traits, however, often exhibit characteristics that make their use problematic. For example, the distribution of the trait may be censored, highly skewed, or contaminated w...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20141

    authors: Allen AS,Martin ER,Qin X,Li YJ

    更新日期:2006-04-01 00:00:00

  • Genetic epidemiology of Menkes disease.

    abstract::Copper incorporation studies were performed on individuals from 58 pedigrees, comprising 140 sibships. As previously reported, there is considerable overlap between heterozygotes and normal homozygotes. Segregation analysis supports recessive inheritance of disease, with residual heritability for 64Cu uptake in cultur...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370030403

    authors: Horn N,Morton NE

    更新日期:1986-01-01 00:00:00

  • Bias in parameter estimates due to omitting gene-environment interaction terms in case-control studies.

    abstract::Genetic studies are continuing to generate volumes and variety of data that can be used to examine the genetic effects. Often the effect of a genetic variant varies by nongenetic measures, what is traditionally defined as gene-environment interaction (G×E). If the G×E term is neglected, estimates of the main effects c...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22154

    authors: Lobach I

    更新日期:2018-12-01 00:00:00

  • Variance component models for X-linked QTLs.

    abstract::This paper discusses the theory and implementation of a model for mapping X-linked quantitative trait loci (QTL). As a result of X inactivation, a female's body is subdivided into a number of patches. In each patch one of her two X chromosomes is randomly switched off. This smooths the allelic contributions in a heter...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20158

    authors: Lange K,Sobel E

    更新日期:2006-07-01 00:00:00

  • Case-only gene-environment interaction studies: when does association imply mechanistic interaction?

    abstract::Case-only studies are often used to identify interactions between a genetic factor and an environmental factor under the assumption both factors are independent in the population. However, interpreting a statistical association between the genetic and the environmental factors among the cases, as evidence of a mechani...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20484

    authors: VanderWeele TJ,Hernández-Díaz S,Hernán MA

    更新日期:2010-05-01 00:00:00

  • SNP selection in genome-wide and candidate gene studies via penalized logistic regression.

    abstract::Penalized regression methods offer an attractive alternative to single marker testing in genetic association analysis. Penalized regression methods shrink down to zero the coefficient of markers that have little apparent effect on the trait of interest, resulting in a parsimonious subset of what we hope are true perti...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20543

    authors: Ayers KL,Cordell HJ

    更新日期:2010-12-01 00:00:00

  • Meta-analysis of linkage studies.

    abstract::Lander and Kruglyak [1995] gave guidelines for interpreting linkage results based on estimating how often a particular threshold for significance would be exceeded by chance in a single genome scan. What is unknown is how often two or more genome scans would exceed a particular threshold within the same region. We dev...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370170778

    authors: Badner JA,Goldin LR

    更新日期:1999-01-01 00:00:00

  • Replication of genetic associations as pseudoreplication due to shared genealogy.

    abstract::The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between mark...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20400

    authors: Rosenberg NA,Vanliere JM

    更新日期:2009-09-01 00:00:00

  • Kernel Approach for Modeling Interaction Effects in Genetic Association Studies of Complex Quantitative Traits.

    abstract::The etiology of complex traits likely involves the effects of genetic and environmental factors, along with complicated interaction effects between them. Consequently, there has been interest in applying genetic association tests of complex traits that account for potential modification of the genetic effect in the pr...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21901

    authors: Broadaway KA,Duncan R,Conneely KN,Almli LM,Bradley B,Ressler KJ,Epstein MP

    更新日期:2015-07-01 00:00:00

  • Identifying genetic interactions in genome-wide data using Bayesian networks.

    abstract::It is believed that interactions among genes (epistasis) may play an important role in susceptibility to common diseases (Moore and Williams [2002]. Ann Med 34:88-95; Ritchie et al. [2001]. Am J Hum Genet 69:138-147). To study the underlying genetic variants of diseases, genome-wide association studies (GWAS) that sim...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20514

    authors: Jiang X,Barmada MM,Visweswaran S

    更新日期:2010-09-01 00:00:00

  • Model selection and Bayesian methods in statistical genetics: summary of group 11 contributions to Genetic Analysis Workshop 15.

    abstract::The research presented in group 11 of the Genetic Analysis Workshop 15 (GAW15) falls into two major themes: Model selection approaches for gene mapping (both Bayesian and Frequentist); and other Bayesian methods. These methods either allow relaxation of some of the common assumptions, such as mode of inheritance, for ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章,评审

    doi:10.1002/gepi.20285

    authors: Swartz MD,Thomas DC,Daw EW,Albers K,Charlesworth JC,Dyer TC,Fridley BL,Govil M,Kraft P,Kwon S,Logue MW,Oh C,Pique-Regi R,Saba L,Schumacher FR,Uh HW

    更新日期:2007-01-01 00:00:00

  • A multipoint method for meta-analysis of genetic association studies.

    abstract::Meta-analyses of genetic association studies are usually performed using a single polymorphism at a time, even though in many cases the individual studies report results from partially overlapping sets of polymorphisms. We present here a multipoint (or multilocus) method for multivariate meta-analysis of published pop...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20531

    authors: Bagos PG,Liakopoulos TD

    更新日期:2010-11-01 00:00:00

  • Effect of linkage disequilibrium between markers in linkage and association analyses.

    abstract::Contributions to Group 17 of the Genetic Analysis Workshop 15 considered dense markers in linkage disequilibrium (LD) in the context of either linkage or association analysis. Three contributions reported on methods for modeling LD or selecting a subset of markers in linkage equilibrium to perform linkage analysis. Wh...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20291

    authors: Dupuis J,Albers K,Allen-Brady K,Cho K,Elston RC,Kappen HJ,Tang H,Thomas A,Thomson G,Tsung E,Yang Q,Zhang W,Zhao K,Zheng G,Ziegler JT

    更新日期:2007-01-01 00:00:00

  • Effect of polygenes on Xiong's transmission disequilibrium test of a QTL in nuclear families with multiple children.

    abstract::The transmission disequilibrium test (TDT), originally developed for mapping disease genes, has recently been extended to identify quantitative trait loci (QTL). For quantitative traits important for human health, generally multiple QTLs are involved. In the investigation of the statistical properties of the TDT, back...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1032

    authors: Deng HW,Li J,Recker RR

    更新日期:2001-11-01 00:00:00

  • A combination test for detection of gene-environment interaction in cohort studies.

    abstract::Identifying gene-environment (G-E) interactions can contribute to a better understanding of disease etiology, which may help researchers develop disease prevention strategies and interventions. One big criticism of studying G-E interaction is the lack of power due to sample size. Studies often restrict the interaction...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22043

    authors: Coombes B,Basu S,McGue M

    更新日期:2017-07-01 00:00:00

  • POLARIS: Polygenic LD-adjusted risk score approach for set-based analysis of GWAS data.

    abstract::Polygenic risk scores (PRSs) are a method to summarize the additive trait variance captured by a set of SNPs, and can increase the power of set-based analyses by leveraging public genome-wide association study (GWAS) datasets. PRS aims to assess the genetic liability to some phenotype on the basis of polygenic risk fo...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22117

    authors: Baker E,Schmidt KM,Sims R,O'Donovan MC,Williams J,Holmans P,Escott-Price V,Consortium WTG

    更新日期:2018-06-01 00:00:00

  • Optimized selection of unrelated subjects for whole-genome sequencing studies of rare high-penetrance alleles.

    abstract::Sequencing studies using whole-genome or exome scans are still more expensive than genome-wide association studies on a per-subject basis. As a result, only a subset of subjects from a larger study will be selected for sequencing. To perform an agnostic investigation of the entire genome, subjects may be selected that...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21641

    authors: Edwards TL,Li C

    更新日期:2012-07-01 00:00:00

  • Identifying SNPs predictive of phenotype using random forests.

    abstract::There has been a great interest and a few successes in the identification of complex disease susceptibility genes in recent years. Association studies, where a large number of single-nucleotide polymorphisms (SNPs) are typed in a sample of cases and controls to determine which genes are associated with a specific dise...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20041

    authors: Bureau A,Dupuis J,Falls K,Lunetta KL,Hayward B,Keith TP,Van Eerdewegh P

    更新日期:2005-02-01 00:00:00

  • Power of the linkage test for a heterogeneous disorder due to two independent inherited causes: a simulation study.

    abstract::We have conducted a simulation study in small pedigrees to investigate the power to detect linkage and heterogeneity for a disorder due to either one of two independent disease loci. We have considered a highly polymorphic marker locus (PIC = 70%) linked to one disease locus and unlinked to the second. The power to de...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370070306

    authors: Martinez M,Goldin LR

    更新日期:1990-01-01 00:00:00

  • Inflated type I error rates when using aggregation methods to analyze rare variants in the 1000 Genomes Project exon sequencing data in unrelated individuals: summary results from Group 7 at Genetic Analysis Workshop 17.

    abstract::As part of Genetic Analysis Workshop 17 (GAW17), our group considered the application of novel and standard approaches to the analysis of genotype-phenotype association in next-generation sequencing data. Our group identified a major issue in the analysis of the GAW17 next-generation sequencing data: type I error and ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20650

    authors: Tintle N,Aschard H,Hu I,Nock N,Wang H,Pugh E

    更新日期:2011-01-01 00:00:00

  • Detecting epistatic interactions contributing to quantitative traits.

    abstract::The restricted partition method (RPM) is a partitioning algorithm for examining multi-locus genotypes as (potentially non-additive) predictors of a quantitative trait. The motivating application was to develop a robust method to examine quantitative phenotypes for epistasis (gene-gene interactions), but the method can...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章,评审

    doi:10.1002/gepi.20006

    authors: Culverhouse R,Klein T,Shannon W

    更新日期:2004-09-01 00:00:00

  • Use of variable marker density, principal components, and neural networks in the dissection of disease etiology.

    abstract::Several approaches were taken to identify the loci contributing to the quantitative and qualitative phenotypes in the Genetic Analysis Workshop 12 simulated data set. To identify possible quantitative trait loci (QTL), the quantitative traits were analyzed using SOLAR. The four replicates identified as the "best repli...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.2001.21.s1.s732

    authors: Pankratz N,Kirkwood SC,Flury L,Koller DL,Foroud T

    更新日期:2001-01-01 00:00:00