Lessons learned from Genetic Analysis Workshop 17: transitioning from genome-wide association studies to whole-genome statistical genetic analysis.


:Genetic Analysis Workshop 17 (GAW17) focused on the transition from genome-wide association study designs and methods to the study designs and statistical genetic methods that will be required for the analysis of next-generation sequence data including both common and rare sequence variants. In the 166 contributions to GAW17, a wide variety of statistical methods were applied to simulated traits in population- and family-based samples, and results from these analyses were compared to the known generating model. In general, many of the statistical genetic methods used in the population-based sample identified causal sequence variants (SVs) when the estimated locus-specific heritability, as measured in the population-based sample, was greater than about 0.08. However, SVs with locus-specific heritabilities less than 0.03 were rarely identified consistently. In the family-based samples, many of the methods detected SVs that were rarer than those detected in the population-based sample, but the estimated locus-specific heritabilities for these rare SVs, as measured in the family-based samples, were substantially higher (>0.2) than their corresponding heritabilities in the population-based samples. Substantial inflation of the type I error rate was observed across a wide variety of statistical methods. Although many of the contributions found little inflation in type I error for Q4, a trait with no causal SVs, type I error rates for Q1 and Q2 were well above their nominal levels with the inflation for Q1 being higher than that for Q2. It seems likely that this inflation in type I error is due to correlations among SVs.


Genet Epidemiol


Genetic epidemiology


Wilson AF,Ziegler A




Has Abstract


2011-01-01 00:00:00








35 Suppl 1


  • Genetic epidemiology of autosomal recessive spastic ataxia of Charlevoix-Saguenay in northeastern Quebec.

    abstract::Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a disorder that has an elevated frequency in Saguenay-Lac-St-Jean (SLSJ) and Charlevoix, two geographically isolated regions in the past of northeastern Quebec. The incidence at birth and the carrier rate in SLSJ were estimated at 1/1,932 liveborn i...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: De Braekeleer M,Giasson F,Mathieu J,Roy M,Bouchard JP,Morgan K

    更新日期:1993-01-01 00:00:00

  • Lifestyle and blood pressure levels in male twins in Utah.

    abstract::Healthy male monozygotic (MZ) and dizygotic (DZ) twin pairs (MZ pairs = 77; DZ pairs = 88) were studied to assess the effect of dietary intake, physical activity, physical fitness, body mass index (BMI), sum of the triceps and subscapular skinfold measurements, alcohol and caffeine consumption, and smoking patterns on...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Slattery ML,Bishop DT,French TK,Hunt SC,Meikle AW,Williams RR

    更新日期:1988-01-01 00:00:00

  • Sequencing and imputation in GWAS: Cost-effective strategies to increase power and genomic coverage across diverse populations.

    abstract::A key aim for current genome-wide association studies (GWAS) is to interrogate the full spectrum of genetic variation underlying human traits, including rare variants, across populations. Deep whole-genome sequencing is the gold standard to fully capture genetic variation, but remains prohibitively expensive for large...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Quick C,Anugu P,Musani S,Weiss ST,Burchard EG,White MJ,Keys KL,Cucca F,Sidore C,Boehnke M,Fuchsberger C

    更新日期:2020-09-01 00:00:00

  • Two adaptive weighting methods to test for rare variant associations in family-based designs.

    abstract::Although next-generation DNA sequencing technologies have made rare variant association studies feasible and affordable, the development of powerful statistical methods for rare variant association studies is still under way. Most of the existing methods for rare variant association studies compare the number of rare ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Fang S,Sha Q,Zhang S

    更新日期:2012-07-01 00:00:00

  • A novel association test for multiple secondary phenotypes from a case-control GWAS.

    abstract::In the past decade, many genome-wide association studies (GWASs) have been conducted to explore association of single nucleotide polymorphisms (SNPs) with complex diseases using a case-control design. These GWASs not only collect information on the disease status (primary phenotype, D) and the SNPs (genotypes, X), but...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章,随机对照试验


    authors: Ray D,Basu S

    更新日期:2017-07-01 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


    authors: Roeder K,Devlin B,Wasserman L

    更新日期:2007-11-01 00:00:00

  • Mapping alcoholism genes using linkage/linkage disequilibrium analysis.

    abstract::Using a recently developed semiparametric method for combined linkage/linkage-disequilibrium analysis, we analyzed the Collaborative Study on the Genetics of Alcoholism data subset developed for Genetic Analysis Workshop 11 (GAW11). This semiparametric approach estimates recombination fractions for linkage, marker log...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Aragaki C,Quiaoit F,Hsu L,Zhao LP

    更新日期:1999-01-01 00:00:00

  • eQuIPS: eQTL Analysis Using Informed Partitioning of SNPs - A Fully Bayesian Approach.

    abstract::We develop a Bayesian multi-SNP Markov chain Monte Carlo approach that allows published functional significance scores to objectively inform single nucleotide polymorphism (SNP) prior effect sizes in expression quantitative trait locus (eQTL) studies. We developed the Normal Gamma prior to allow the inclusion of funct...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Boggis EM,Milo M,Walters K

    更新日期:2016-05-01 00:00:00

  • Increasing the power of identifying gene x gene interactions in genome-wide association studies.

    abstract::In this paper we investigate the power to identify gene x gene interactions in genome-wide association studies. In our analysis we focus on two-stage analyses: analyses in which we only test for interactions between single nucleotide polymorphisms that show some marginal effect. We give two algorithms to compute signi...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Kooperberg C,Leblanc M

    更新日期:2008-04-01 00:00:00

  • The impact of improved microarray coverage and larger sample sizes on future genome-wide association studies.

    abstract::Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with complex traits. However, the genetic heritability of most of these traits remains unexplained. To help guide future studies, we address the crucial question of whether future GWAS can detect new SNP assoc...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Lindquist KJ,Jorgenson E,Hoffmann TJ,Witte JS

    更新日期:2013-05-01 00:00:00

  • Power and sample size calculations for SNP association studies with censored time-to-event outcomes.

    abstract::For many clinical studies in cancer, germline DNA is prospectively collected for the purpose of discovering or validating single-nucleotide polymorphisms (SNPs) associated with clinical outcomes. The primary clinical endpoint for many of these studies are time-to-event outcomes such as time of death or disease progres...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Owzar K,Li Z,Cox N,Jung SH

    更新日期:2012-09-01 00:00:00

  • Genetic heterogeneity in Alzheimer's disease: a grade of membership analysis.

    abstract::Grade of membership analysis (GoM) may have particular relevance for genetic epidemiology. The method can flexibly relate genetic markers, clinical features, and environmental exposures to possible subtypes of disease termed pure types even when population allele frequencies and penetrance functions are not known. Hen...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Corder EH,Woodbury MA

    更新日期:1993-01-01 00:00:00

  • Mantel statistics to correlate gene expression levels from microarrays with clinical covariates.

    abstract::Mantel statistics provide an additional step to standard approaches in the analysis of gene expression and covariate data, allow the calculation of standard statistics such as correlation, partial correlation, and regression coefficients, and, with permutation tests, provide P values for these statistics to relate the...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Shannon WD,Watson MA,Perry A,Rich K

    更新日期:2002-06-01 00:00:00

  • Evaluation of genetic and environmental effects using GEE and APM methods.

    abstract::Two analytic methods were used in the Problem 2 data set. First, generalized estimating equations (GEE) modelling was developed to adjust for familial correlation in regressions evaluating candidate genes and an environmental factor. Second, the affected-pedigree-member (APM) method was used to identify chromosomal re...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Bull SB,Chapman NH,Greenwood CM,Darlington GA

    更新日期:1995-01-01 00:00:00

  • Accounting for population stratification in DNA methylation studies.

    abstract::DNA methylation is an important epigenetic mechanism that has been linked to complex diseases and is of great interest to researchers as a potential link between genome, environment, and disease. As the scale of DNA methylation association studies approaches that of genome-wide association studies, issues such as popu...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Barfield RT,Almli LM,Kilaru V,Smith AK,Mercer KB,Duncan R,Klengel T,Mehta D,Binder EB,Epstein MP,Ressler KJ,Conneely KN

    更新日期:2014-04-01 00:00:00

  • Monte Carlo analysis on a large pedigree.

    abstract::Monte Carlo methods for linkage and segregation analysis are applied to the HGAR1 pedigree. To address these data, the methods are extended in several ways. The results are compared with those provided by PAP. ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Thompson EA,Lin S,Olshen AB,Wijsman EM

    更新日期:1993-01-01 00:00:00

  • Allelic association patterns for a dense SNP map.

    abstract::A dense set of 5,000 SNPs on a 10-Mb region of human chromosome 20 has been typed on samples of African Americans, East Asians, and United Kingdom Caucasians. There are departures from Hardy-Weinberg equilibrium beyond the level at which markers are often discarded because of possible genotyping errors. The observatio...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Weir BS,Hill WG,Cardon LR,SNP Consortium.

    更新日期:2004-12-01 00:00:00

  • Identification of susceptibility loci contributing to a complex disease using conventional segregation, linkage, and association methods.

    abstract::We set out to apply conventional analytic methods to a GAW data set of nuclear families with an oligogenic disease that has a population prevalence of 0.023. We chose methods generally applied to disorders with at least one major gene. Our approaches included: 1) complex segregation analysis under two models of ascert...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Falk CT,Ashley A,Lamb N,Sherman SL

    更新日期:1995-01-01 00:00:00

  • Risk factors for atherosclerosis in twins.

    abstract::We performed multivariate genetic analyses of cardiovascular risk factors from two sets of data on US and Australian female twins. Similar models for body mass index (BMI), serum low density (LDL) and high density (HDL) lipoproteins, including age as a covariate, were fitted successfully to both groups. These suggeste...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Duffy DL,O'Connell DL,Heller RF,Martin NG

    更新日期:1993-01-01 00:00:00

  • Direct genetic effects and their estimation from matched case-control data.

    abstract::In genetic association studies, a single marker is often associated with multiple, correlated phenotypes (e.g., obesity and cardiovascular disease, or nicotine dependence and lung cancer). A pervasive question is then whether that marker exerts independent effects on all phenotypes. In this paper, we address this ques...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Berzuini C,Vansteelandt S,Foco L,Pastorino R,Bernardinelli L

    更新日期:2012-09-01 00:00:00

  • Combining family- and population-based imputation data for association analysis of rare and common variants in large pedigrees.

    abstract::In the last two decades, complex traits have become the main focus of genetic studies. The hypothesis that both rare and common variants are associated with complex traits is increasingly being discussed. Family-based association studies using relatively large pedigrees are suitable for both rare and common variant id...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Saad M,Wijsman EM

    更新日期:2014-11-01 00:00:00

  • Analysis of twin data ascertained through probands: the double-entry approach.

    abstract::Twin pairs are sometimes included in studies because at least one of them is a proband, and conventionally the analysis of the data is based on the conditional distribution of the co twin given the proband. In the case of more than one proband in each pair, an often used "ad hoc" method of analysis is to allow each tw...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Hindsberger C,Bryld LE

    更新日期:2003-11-01 00:00:00

  • Regressive logistic modeling of familial aggregation for asthma in 7,394 population-based nuclear families.

    abstract::The aim of this population-based study was to determine whether asthma aggregates in families, and if so, whether aggregation was consistent with environmental and/or genetic etiologies. Data were from 7,394 nuclear families (41,506 individuals) from the 1968 Tasmanian Asthma Survey, in which all Tasmanian schoolchild...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Jenkins MA,Hopper JL,Giles GG

    更新日期:1997-01-01 00:00:00

  • Method for calculating risk associated with family history of a disease.

    abstract::A method is described for estimating excess relative risks of a disease from familial factors. Beginning with population-based series of cases and controls, a cohort of each subject's relatives is formed and checked for disease against a population based registry. The disease experience of the cohort formed from each ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Kerber RA

    更新日期:1995-01-01 00:00:00

  • Pooling data and linkage analysis in the chromosome 5q candidate region for asthma.

    abstract::We investigated a variety of methods for pooling data from eight data sets (n = 5,424 subjects) to validate evidence for linkage of markers in the cytokine cluster on chromosome 5q31-33 to asthma and asthma-associated phenotypes. Chromosome 5 markers were integrated into current genetic linkage and physical maps, and ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章,meta分析


    authors: Jacobs KB,Burton PR,Iyengar SK,Elston RC,Palmer LJ

    更新日期:2001-01-01 00:00:00

  • Genetic epidemiology with a capital "E".

    abstract::Three characteristics of genetic epidemiology that distinguish it from its parent disciplines are a focus on population-based research, a focus on the joint effects of genes and the environment, and the incorporation of the underlying biology of the disease into its conceptual models. These principles are illustrated ...

    journal_title:Genetic epidemiology



    authors: Thomas DC

    更新日期:2000-12-01 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


    authors: Culverhouse R,Klein T,Shannon W

    更新日期:2004-09-01 00:00:00

  • Analysis of two-locus traits under heterogeneity for recessive versus dominant inheritance.

    abstract::Complex traits have been modeled under various modes of two-locus inheritance. One example of a two-locus threshold model is the situation where an individual is susceptible to a disease trait if he or she carries three or more disease alleles. Under this model, if each locus is examined individually the inheritance a...

    journal_title:Genetic epidemiology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Leal SM,Ott J

    更新日期:1997-01-01 00:00:00

  • 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 op...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: He Z,Lee S,Zhang M,Smith JA,Guo X,Palmas W,Kardia SLR,Ionita-Laza I,Mukherjee B

    更新日期:2017-12-01 00:00:00

  • Immunoglobulin allotyping (Gm, Km) of GAW5 families.

    abstract::The following Gm and Km immunoglobulin allotypes were determined on the Genetic Analysis Workshop 5 insulin-dependent diabetes mellitus (GAW5 IDDM) families: G1m (1,2,3,17), G2m (23), G3m (5,10,11,13,14,21,28) and Km (1,3). Since the allotype G2m (23) has been rarely studied, due to paucity of typing reagents, it was ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Field LL,Dugoujon JM

    更新日期:1989-01-01 00:00:00