Exploiting pleiotropy to map genes for oligogenic phenotypes using extended pedigree data.

Abstract:

:We investigated the utility of two approaches for exploiting pleiotropy to search for genes influencing related traits. To do this we first assessed the genetic correlations among a set of five closely related quantitative traits (Q1, Q2, Q3, Q4, Q5). We then used the genetic correlations among these five traits both to remove the common genetic effects of the four remaining traits, thereby identifying the unique genetic contribution to each trait, and to extract a synthetic phenotype which exploits the shared genetic information (pleiotropy) among these five traits. After obtaining these conditional traits, we then searched for evidence of quantitative trait loci (QTLs) (using variance component linkage) influencing the unique residual genetic component for each trait as well as those influencing the expression of the synthetic traits. From this work, we conclude that the removal of the common genetic effects of other traits in a group may be of greater utility when the majority of the pleiotropy initially detected between traits is attributable to the shared additive effects of polygenes, rather than to those of major loci. By contrast, decomposition of the genetic covariance matrix to its principal components is a greater utility when the majority of pleiotropy is attributable to major loci.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

authors

Comuzzie AG,Mahaney MC,Almasy L,Dyer TD,Blangero J

doi

10.1002/(SICI)1098-2272(1997)14:6<975::AID-GEPI69>

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

975-80

issue

6

eissn

0741-0395

issn

1098-2272

pii

10.1002/(SICI)1098-2272(1997)14:6<975::AID-GEPI69>

journal_volume

14

pub_type

杂志文章
  • 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

  • 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

  • Linkage disequilibrium between DNA markers at the low-density lipoprotein receptor gene.

    abstract::We determined pairwise linkage disequilibria between 12 restriction fragment length polymorphism (RFLP) markers at or near the low-density lipoprotein receptor (LDLR) locus on chromosome 19p13.2-13.1 in 92 unrelated individuals. Of these 12 RFLPs, two were newly identified under a cosmid-based strategy designed to scr...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370070114

    authors: Hegele RA,Plaetke R,Lalouel JM

    更新日期:1990-01-01 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

  • A new association test based on Chi-square partition for case-control GWA studies.

    abstract::In case-control genetic association studies, the robust procedure, Pearson's Chi-square test, is commonly used for testing association between disease status and genetic markers. However, this test does not take the possible trend of relative risks, which are due to genotype, into account. On the contrary, although Co...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20615

    authors: Chen Z

    更新日期:2011-11-01 00:00:00

  • 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 subse...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22086

    authors: Saffari A,Silver MJ,Zavattari P,Moi L,Columbano A,Meaburn EL,Dudbridge F

    更新日期:2018-02-01 00:00:00

  • Regressive logistic and proportional hazards disease models for within-family analyses of measured genotypes, with application to a CYP17 polymorphism and breast cancer.

    abstract::Various statistical methods have been proposed to evaluate associations between measured genetic variants and disease, including some using family designs. For breast cancer and rare variants, we applied a modified segregation analysis method that uses the population cancer incidence and population-based case families...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10222

    authors: Cui JS,Spurdle AB,Southey MC,Dite GS,Venter DJ,McCredie MR,Giles GG,Chenevix-Trench G,Hopper JL

    更新日期:2003-04-01 00:00:00

  • Trends in prenatal diagnosis of Down syndrome and other autosomal trisomies in Scotland 1990 to 1994, with associated cytogenetic and epidemiological findings.

    abstract::The present report summarizes findings on 670 cases of autosomal trisomy diagnosed in Scotland, with actual or expected dates of delivery in 1990 to 1994 inclusive. Cases were notified by cytogenetic service laboratories. There were 277 prenatal and 369 postnatal diagnoses and 24 spontaneous losses. Excluding the latt...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1999)16:2<179::AID-GEPI5>3

    authors: Carothers AD,Boyd E,Lowther G,Ellis PM,Couzin DA,Faed MJ,Robb A

    更新日期:1999-01-01 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

  • 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

  • Evidence for further breast cancer susceptibility genes in addition to BRCA1 and BRCA2 in a population-based study.

    abstract::We used data from a population based series of breast cancer patients to investigate the genetic models that can best explain familial breast cancer not due to the BRCA1 and BRCA2 genes. The data set consisted of 1,484 women diagnosed with breast cancer under age 55 registered in the East Anglia Cancer registry betwee...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1014

    authors: Antoniou AC,Pharoah PD,McMullan G,Day NE,Ponder BA,Easton D

    更新日期:2001-07-01 00:00:00

  • Progress toward resolving the possible linkage of multiple endocrine neoplasia type 2A to haptoglobin and group-specific loci: use of restriction fragment length polymorphisms extends exclusion region.

    abstract::In an earlier paper, positive but nonsignificant lod scores were found in pair-wise linkage tests between multiple endocrine neoplasia type 2A (MEN-2A) and both the haptoglobin (HP) locus on chromosome 16 and group-specific component (GC) locus on chromosome 4. Recently discovered restriction fragment length polymorph...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370030306

    authors: Kidd KK,Kidd JR,Castiglione CM,Pakstis AJ,Sparkes RS

    更新日期:1986-01-01 00:00:00

  • Comparison of the QTDT analysis for IgE in the CSGA data set.

    abstract::Over the past few years at least 13 transmission/disequilibrium test (TDT)-based tests have been developed for quantitative (Q) traits for the assessment of association or linkage in the presence of the other. A total of six of these QTDT methods were used to analyze log10IgE in the Collaborative Study on the Genetics...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.2001.21.s1.s312

    authors: Page GP,Wilcox MA,Occhiuto J,Adak S,Neuberg D,Bajorunaite R,George V

    更新日期:2001-01-01 00:00:00

  • Family-based association tests for qualitative and quantitative traits using single-nucleotide polymorphism and microsatellite data.

    abstract::Using the Genetic Analysis Workshop 12 simulated data, we contrasted results for association tests in nuclear families and extended pedigrees using single-nucleotide polymorphism (SNP) data, and we compared results for different trait definitions, for outbred and isolate populations, and for SNP and microsatellite dat...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.2001.21.s1.s364

    authors: Wilk JB,Volcjak JS,Myers RH,Maher NE,Knowlton BA,Heard-Costa NL,Demissie S,Cupples LA,DeStefano AL

    更新日期:2001-01-01 00:00:00

  • 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

  • Gene-dropping vs. empirical variance estimation for allele-sharing linkage statistics.

    abstract::In this study, we compare the statistical properties of a number of methods for estimating P-values for allele-sharing statistics in non-parametric linkage analysis. Some of the methods are based on the normality assumption, using different variance estimation methods, and others use simulation (gene-dropping) to find...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20177

    authors: Jung J,Weeks DE,Feingold E

    更新日期:2006-12-01 00:00:00

  • Information on ancestry from genetic markers.

    abstract::It is possible to estimate the proportionate contributions of ancestral populations to admixed individuals or populations using genetic markers, but different loci and alleles vary considerably in the amount of information that they provide. Conventionally, the allele frequency difference between parental populations ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10319

    authors: Pfaff CL,Barnholtz-Sloan J,Wagner JK,Long JC

    更新日期:2004-05-01 00:00:00

  • Two common polymorphisms in the APO A-IV coding gene: their evolution and linkage disequilibrium.

    abstract::Human apolipoprotein A-IV (APO A-IV) exhibits a common protein polymorphism detectable by isoelectric focusing (IEF) due to a single base substitution at codon 360 which replaces the frequently occurring glutamine residue (allele 1) with histidine (allele 2). Recently, sequence analysis of the APO A-IV coding region h...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370090503

    authors: Kamboh MI,Hamman RF,Ferrell RE

    更新日期:1992-01-01 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

  • Integration of multiomic annotation data to prioritize and characterize inflammation and immune-related risk variants in squamous cell lung cancer.

    abstract::Clinical trial results have recently demonstrated that inhibiting inflammation by targeting the interleukin-1β pathway can offer a significant reduction in lung cancer incidence and mortality, highlighting a pressing and unmet need to understand the benefits of inflammation-focused lung cancer therapies at the genetic...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22358

    authors: Sun R,Xu M,Li X,Gaynor S,Zhou H,Li Z,Bossé Y,Lam S,Tsao MS,Tardon A,Chen C,Doherty J,Goodman G,Bojesen SE,Landi MT,Johansson M,Field JK,Bickeböller H,Wichmann HE,Risch A,Rennert G,Arnold S,Wu X,Melander O,

    更新日期:2021-02-01 00:00:00

  • Conditional multipoint linkage analysis using affected sib pairs: an alternative approach.

    abstract::Recently, Liang et al. ([2001b] Genet. Epidemiol. 21:105-122) proposed a conditional approach to assess linkage evidence on the target region by incorporating linkage information from an unlinked (reference) region using allele shared IBD (identity-by-decent) from affected sib pairs. This is carried out by conditionin...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10305

    authors: Chiu YF,Liang KY

    更新日期:2004-02-01 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

    doi:10.1002/gepi.1370120633

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

    更新日期:1995-01-01 00:00:00

  • APO B 3' HVR polymorphism in healthy population: relationships to serum lipid levels.

    abstract::We have analyzed allele frequency distribution at the hypervariable locus 3' to the apolipoprotein B gene in a healthy population sample (241 women and 246 men) from the Belgrade area. The bimodal distribution of sixteen different hypervariable region (HVR) alleles and the heterozygosity index (average 0.76) in both s...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1998)15:2<113::AID-GEPI1>3

    authors: Alavantić D,Glisić S,Kandić I

    更新日期:1998-01-01 00:00:00

  • Evaluation of methods accounting for population structure with pedigree data and continuous outcomes.

    abstract::Methods to account for population structure (PS) in genome-wide association studies have been well developed in samples of unrelated individuals, but when a sample is composed of families, the task of finding and accounting for PS is not as straight forward. Family-based tests that condition on parental genotypes or t...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20590

    authors: Peloso GM,Dupuis J,Lunetta KL

    更新日期:2011-09-01 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

  • 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

  • Meta-analysis by combining p-values: simulated linkage studies.

    abstract::Meta-analysis has been little explored to make an overall assessment of linkage from different studies. In practice, it is likely that published linkage studies will only report p-values. We compared the performance of the widely used Fisher method for combining p-values with that of pooling raw data. More loci were c...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章,meta分析

    doi:10.1002/gepi.1370170798

    authors: Guerra R,Etzel CJ,Goldstein DR,Sain SR

    更新日期:1999-01-01 00:00:00

  • Novel likelihood ratio tests for screening gene-gene and gene-environment interactions with unbalanced repeated-measures data.

    abstract::There has been extensive literature on modeling gene-gene interaction (GGI) and gene-environment interaction (GEI) in case-control studies with limited literature on statistical methods for GGI and GEI in longitudinal cohort studies. We borrow ideas from the classical two-way analysis of variance literature to address...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21744

    authors: Ko YA,Saha-Chaudhuri P,Park SK,Vokonas PS,Mukherjee B

    更新日期:2013-09-01 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

    doi:10.1002/gepi.21844

    authors: Saad M,Wijsman EM

    更新日期:2014-11-01 00:00:00

  • Genome-wide approaches for identifying interacting susceptibility regions for asthma.

    abstract::A genome-wide correlation analysis and cluster analysis were utilized to determine chromosomal regions that had similar nonparametric linkage scores across families in order to locate interacting susceptibility loci for asthma. Conditional analysis was performed to detect any increase in lod score over baseline. Eight...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.2001.21.s1.s266

    authors: Colilla S,Tsalenko A,Pluznikov A,Cox NJ

    更新日期:2001-01-01 00:00:00