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. When all markers were used without modeling LD, inflated evidence for linkage was observed when parental genotypes were missing. All methods for handling LD led to some decreased linkage evidence. Two groups performed a genome-wide association scan using either mixed models to account for known or unknown relatedness between individuals, trend tests or combination statistics. All methods failed to detect four of the eight simulated loci because of low LD in some regions. Three groups performed association analysis using simulated dense markers on chromosome 6, where a simulated HLA-DRB1 locus played a major role in disease susceptibility along with two additional loci of smaller effect. The overall conditional genotype method correctly identified both additional loci while a novel transmission disequilibrium test-statistic to combine studies with non-overlapping markers identified one HLA locus after stratifying on the parental HLA-DRB1 genotypes; LD mapping using the Malécot model mapped two loci in this region, even when using greatly reduced marker density. While LD between markers appears to be a nuisance that may cause spurious linkage results with missing parental genotypes in linkage analysis, association analysis thrives on LD, and disease genes fail to be detected in regions of low LD.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

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

doi

10.1002/gepi.20291

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

S139-48

eissn

0741-0395

issn

1098-2272

journal_volume

31 Suppl 1

pub_type

杂志文章
  • Demonstration of a common major gene with pleiotropic effects on immunoglobulin E levels and allergy.

    abstract::Atopic disease is generally recognized to be familial, although specific genetic components have yet to be identified. High levels of a unique class of immunoglobulins, immunoglobulin E (IgE), have been shown to be associated with allergies. Several investigators have reported evidence indicating a recessive regulator...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370020402

    authors: Borecki IB,Rao DC,Lalouel JM,McGue M,Gerrard JW

    更新日期:1985-01-01 00:00:00

  • Rank-based robust tests for quantitative-trait genetic association studies.

    abstract::Standard linear regression is commonly used for genetic association studies of quantitative traits. This approach may not be appropriate if the trait, on its original or transformed scales, does not follow a normal distribution. A rank-based nonparametric approach that does not rely on any distributional assumptions c...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21723

    authors: Li Q,Li Z,Zheng G,Gao G,Yu K

    更新日期:2013-05-01 00:00:00

  • Familial analysis of eosinophilia caused by helminthic parasites.

    abstract::A highly significant familial aggregation of eosinophil levels (X2(3) = 38.00) was detected in a sample from three Brazilian populations with a high incidence of helminthic parasitism. The data were unable to resolve genetic or common environment causation due to the lack of environmental concomitant variables. Result...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370090305

    authors: Moro-Furlani AM,Krieger H

    更新日期:1992-01-01 00:00:00

  • Joint analysis of multiple phenotypes using a clustering linear combination method based on hierarchical clustering.

    abstract::Emerging evidence suggests that a genetic variant can affect multiple phenotypes, especially in complex human diseases. Therefore, joint analysis of multiple phenotypes may offer new insights into disease etiology. Recently, many statistical methods have been developed for joint analysis of multiple phenotypes, includ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22263

    authors: Li X,Zhang S,Sha Q

    更新日期:2020-01-01 00:00:00

  • A two-locus model for familial Alzheimer's disease?

    abstract::The present findings for familial Alzheimer's disease suggest a possible linkage to gene(s) on chromosome 21 for the early onset form and to chromosome 19 for the late onset. Since these results are not unequivocal, possible alternative hypotheses include the effect of genetic heterogeneity or of an oligogenic model o...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370100618

    authors: Macciardi F,Cavallini MC

    更新日期:1993-01-01 00:00:00

  • Genome-wide family-based linkage analysis of exome chip variants and cardiometabolic risk.

    abstract::Linkage analysis of complex traits has had limited success in identifying trait-influencing loci. Recently, coding variants have been implicated as the basis for some biomedical associations. We tested whether coding variants are the basis for linkage peaks of complex traits in 42 African-American (n = 596) and 90 His...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21801

    authors: Hellwege JN,Palmer ND,Raffield LM,Ng MC,Hawkins GA,Long J,Lorenzo C,Norris JM,Ida Chen YD,Speliotes EK,Rotter JI,Langefeld CD,Wagenknecht LE,Bowden DW

    更新日期:2014-05-01 00:00:00

  • The power of iterated generalized least squares (GLS) method to detect direct relationships in the analysis of correlated quantitative traits.

    abstract::We examined the power of the stepwise iterated generalized least squares (GLS) method by modeling the relationship between quantitative traits and other variables using the simulated data for Problem 2A. The comparison between the generating model provided by the workshop and the results of the stepwise iterated GLS m...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1997)14:6<797::AID-GEPI39>

    authors: He Q,Nemesure BB,Mendell NR

    更新日期:1997-01-01 00:00:00

  • Multipoint analysis using affected sib pairs: incorporating linkage evidence from unlinked regions.

    abstract::In this paper, we proposed a multipoint method to assess evidence of linkage to one region by incorporating linkage evidence from another region. This approach uses affected sib pairs in which the number of alleles shared identical by descent (IBD) is the primary statistic. This generalized estimating equation (GEE) a...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1021

    authors: Liang KY,Chiu YF,Beaty TH,Wjst M

    更新日期:2001-09-01 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

    doi:10.1002/gepi.22045

    authors: Ray D,Basu S

    更新日期:2017-07-01 00:00:00

  • 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

  • Exploring data from genetic association studies using Bayesian variable selection and the Dirichlet process: application to searching for gene × gene patterns.

    abstract::We construct data exploration tools for recognizing important covariate patterns associated with a phenotype, with particular focus on searching for association with gene-gene patterns. To this end, we propose a new variable selection procedure that employs latent selection weights and compare it to an alternative for...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21661

    authors: Papathomas M,Molitor J,Hoggart C,Hastie D,Richardson S

    更新日期:2012-09-01 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

    doi:10.1002/gepi.1370120613

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

    更新日期:1995-01-01 00:00:00

  • 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 wi...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21949

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

    更新日期:2016-02-01 00:00:00

  • Quantitative allelic test--a fast test for very large association studies.

    abstract::Advances in high throughput technology have enabled the generation of unprecedented amounts of genomic data (e.g., next-generation sequence data, transcriptomics, metabolomics, and proteomics), which promises to unravel the genetic architecture of complex traits. These discoveries may lead to novel therapeutic targets...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21768

    authors: Lee SM,Karrison TG,Cox NJ,Im HK

    更新日期:2013-12-01 00:00:00

  • Efficient strategy for detecting gene × gene joint action and its application in schizophrenia.

    abstract::We propose a new approach to detect gene × gene joint action in genome-wide association studies (GWASs) for case-control designs. This approach offers an exhaustive search for all two-way joint action (including, as a special case, single gene action) that is computationally feasible at the genome-wide level and has r...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21779

    authors: Won S,Kwon MS,Mattheisen M,Park S,Park C,Kihara D,Cichon S,Ophoff R,Nöthen MM,Rietschel M,Baur M,Uitterlinden AG,Hofmann A,GROUP Investigators.,Lange C

    更新日期:2014-01-01 00:00:00

  • Analysis of breast cancer pedigrees using affected sibship methods.

    abstract::Haplotype-sharing was examined in sets of affected siblings in the Breast Cancer Linkage Consortium pedigrees [Easton et al., 1993], using both identity-by-descent and identity-by-state methods. Linkage of the disease susceptibility locus to markers on chromosome 17 was confirmed. Substantial genetic heterogeneity was...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370120653

    authors: Barrett JH,Rigby AS

    更新日期:1995-01-01 00:00:00

  • Haplotype kernel association test as a powerful method to identify chromosomal regions harboring uncommon causal variants.

    abstract::For most complex diseases, the fraction of heritability that can be explained by the variants discovered from genome-wide association studies is minor. Although the so-called "rare variants" (minor allele frequency [MAF] < 1%) have attracted increasing attention, they are unlikely to account for much of the "missing h...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21740

    authors: Lin WY,Yi N,Lou XY,Zhi D,Zhang K,Gao G,Tiwari HK,Liu N

    更新日期:2013-09-01 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

  • 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

  • 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

  • Deciphering Genome Environment Wide Interactions Using Exposed Subjects Only.

    abstract::The recent successes of genome-wide association studies (GWAS) have renewed interest in genome environment wide interaction studies (GEWIS) to discover genetic factors that modulate penetrance of environmental exposures to human diseases. Indeed, gene-environment interactions (G × E), which have not been emphasized in...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21890

    authors: Zhao LP,Fan W,Goodman G,Radich J,Martin P

    更新日期:2015-07-01 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

  • Constructing meiotic maps with known error probability.

    abstract::We propose methods to construct meiotic gene maps while controlling the probability of a decision-error. First, a single step gene ordering procedure is presented whose decision-error probability is bounded above by a prespecified threshold. The bound for the error probability is valid under quite general circumstance...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1999)16:3<274::AID-GEPI4>3

    authors: Rogatko A,Babb J,Jordan H,Zacks S

    更新日期:1999-01-01 00:00:00

  • Identification of grouped rare and common variants via penalized logistic regression.

    abstract::In spite of the success of genome-wide association studies in finding many common variants associated with disease, these variants seem to explain only a small proportion of the estimated heritability. Data collection has turned toward exome and whole genome sequencing, but it is well known that single marker methods ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21746

    authors: Ayers KL,Cordell HJ

    更新日期:2013-09-01 00:00:00

  • Hierarchical Bayesian model for rare variant association analysis integrating genotype uncertainty in human sequence data.

    abstract::Next-generation sequencing (NGS) has led to the study of rare genetic variants, which possibly explain the missing heritability for complex diseases. Most existing methods for rare variant (RV) association detection do not account for the common presence of sequencing errors in NGS data. The errors can largely affect ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21871

    authors: He L,Pitkäniemi J,Sarin AP,Salomaa V,Sillanpää MJ,Ripatti S

    更新日期:2015-02-01 00:00:00

  • Bayesian meta-analysis across genome-wide association studies of diverse phenotypes.

    abstract::Genome-wide association studies (GWAS) are a powerful tool for understanding the genetic basis of diseases and traits, but most studies have been conducted in isolation, with a focus on either a single or a set of closely related phenotypes. We describe MetABF, a simple Bayesian framework for performing integrative me...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章,meta分析

    doi:10.1002/gepi.22202

    authors: Trochet H,Pirinen M,Band G,Jostins L,McVean G,Spencer CCA

    更新日期:2019-07-01 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

  • Major locus inheritance of apolipoprotein B in Utah pedigrees.

    abstract::A major locus that determines levels of apolipoprotein B (apoB) was revealed by likelihood analysis on 331 members of 36 pedigrees. The major locus explained 43.2% of the observed variance, with the remainder attributed to random environmental factors. Estimated mean apoB levels (mg/dl) were 110.5 +/- 2.5, 141.9 +/- 4...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370040202

    authors: Hasstedt SJ,Wu L,Williams RR

    更新日期:1987-01-01 00:00:00

  • 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 rout...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22030

    authors: Zhan X,Tong X,Zhao N,Maity A,Wu MC,Chen J

    更新日期:2017-04-01 00:00:00

  • Explorative two-locus linkage analysis suggests a multiplicative interaction between the 7q32 and 16p13 myoclonic seizures-related photosensitivity loci.

    abstract::In traits suspected to be governed by at least two loci, linkage analysis incorporating the joint action of both loci may improve the power to detect linkage, increase the precision of estimating locus positions and provide insight into the underlying etiological mechanism. Recently, we mapped two susceptibility loci ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20190

    authors: Pinto D,Kasteleijn-Nolst Trenité DG,Cordell HJ,Mattheisen M,Strauch K,Lindhout D,Koeleman BP

    更新日期:2007-01-01 00:00:00