Equivalence of the mixed and regressive models for genetic analysis. I. Continuous traits.

Abstract:

:The mixed model of segregation analysis specifies major gene effects and partitions the residual variance into polygenic and environmental components. The model explains familial correlations essentially in terms of genetic causation. The regressive model, on the other hand, is constructed by successively conditioning on ancestral phenotypes and major genes. Familial patterns of dependence are described in terms of correlations without necessarily introducing a particular scheme of causal relationship. These two approaches are compared both theoretically and numerically through computer simulations for the case of continuous traits on nuclear families. The class D regressive model, which is characterized by equal sib-sib correlations, is mathematically and numerically equivalent to the mixed model. The simpler class A regressive model, which is also characterized by equal sib-sib correlations determined in this case by the common parentage, provides good estimates of the mixed model parameters: major gene parameters and residual polygenic heritability, derived from the parent-offspring correlation. However, in the absence of a major gene, the restriction imposed by the class A model on the sibling correlation can affect the conclusions of segregation analysis: False inference of a major gene was observed in two out of ten replicates. Our simulations also indicate that the mixed model allowing for different heritabilities in adults and children leads to correct estimates of the major gene parameters and residual familial correlations (parent-offspring and sib-sib) as specified by the class A model. For all the models studied, major gene effects, when present, are correctly detected and estimated.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

authors

Demenais FM,Bonney GE

doi

10.1002/gepi.1370060505

subject

Has Abstract

pub_date

1989-01-01 00:00:00

pages

597-617

issue

5

eissn

0741-0395

issn

1098-2272

journal_volume

6

pub_type

杂志文章
  • 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

    doi:10.1002/gepi.20300

    authors: Kooperberg C,Leblanc M

    更新日期:2008-04-01 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

    doi:10.1002/(SICI)1098-2272(1997)14:3<317::AID-GEPI9>3

    authors: Jenkins MA,Hopper JL,Giles GG

    更新日期:1997-01-01 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

    doi:10.1002/gepi.21724

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

    更新日期:2013-05-01 00:00:00

  • How can maximum likelihood methods reveal candidate gene effects on a quantitative trait?

    abstract::Different maximum likelihood approaches were used to explore the role of candidate genes in the variability of quantitative trait Q1 while accounting for the effects of age, Q2, and Q3. Segregation analysis, under the class D regressive model, provides evidence for a Mendelian gene effect on the adjusted trait Q1. Res...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370120643

    authors: Martinez M,Abel L,Demenais F

    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

    doi:10.1002/gepi.1370100638

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

    更新日期:1993-01-01 00:00:00

  • SimPEL: Simulation-based power estimation for sequencing studies of low-prevalence conditions.

    abstract::Power estimations are important for optimizing genotype-phenotype association study designs. However, existing frameworks are designed for common disorders, and thus ill-suited for the inherent challenges of studies for low-prevalence conditions such as rare diseases and infrequent adverse drug reactions. These challe...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22129

    authors: Mak L,Li M,Cao C,Gordon P,Tarailo-Graovac M,Bousman C,Wang P,Long Q

    更新日期:2018-07-01 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

  • Maximum-likelihood estimation of haplotype frequencies in nuclear families.

    abstract::The importance of haplotype analysis in the context of association fine mapping of disease genes has grown steadily over the last years. Since experimental methods to determine haplotypes on a large scale are not available, phase has to be inferred statistically. For individual genotype data, several reconstruction te...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10323

    authors: Becker T,Knapp M

    更新日期:2004-07-01 00:00:00

  • A likelihood ratio-based Mann-Whitney approach finds novel replicable joint gene action for type 2 diabetes.

    abstract::The potential importance of the joint action of genes, whether modeled with or without a statistical interaction term, has long been recognized. However, identifying such action has been a great challenge, especially when millions of genetic markers are involved. We propose a likelihood ratio-based Mann-Whitney test t...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21651

    authors: Lu Q,Wei C,Ye C,Li M,Elston RC

    更新日期:2012-09-01 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

  • 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

  • Defining the power limits of genome-wide association scan meta-analyses.

    abstract::Large-scale meta-analyses of genome-wide association scans (GWAS) have been successful in discovering common risk variants with modest and small effects. The detection of lower frequency signals will undoubtedly require concerted efforts of at least similar scale. We investigate the sample size-dictated power limits o...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20627

    authors: Chapman K,Ferreira T,Morris A,Asimit J,Zeggini E

    更新日期:2011-12-01 00:00:00

  • Association and linkage analysis of ICD-10 diagnosis for alcoholism.

    abstract::We analyzed the GAW11 data on alcoholism provided by the Collaborative Study on the Genetics of Alcoholism (COGA) using an extension of a new test of linkage and association for quantitative traits developed by George et al. [1999]. This method determines linkage between marker loci and quantitative traits, when allel...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370170758

    authors: Tiwari HK,Zhu X,Elston RC,Shu Y,George V

    更新日期:1999-01-01 00:00:00

  • An efficient study design to test parent-of-origin effects in family trios.

    abstract::Increasing evidence has shown that genes may cause prenatal, neonatal, and pediatric diseases depending on their parental origins. Statistical models that incorporate parent-of-origin effects (POEs) can improve the power of detecting disease-associated genes and help explain the missing heritability of diseases. In ma...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22060

    authors: Yu X,Chen G,Feng R

    更新日期:2017-11-01 00:00:00

  • Contribution of thermolabile methylenetetrahydrofolate reductase variant to total plasma homocysteine levels in healthy men and women. Inter99 (2).

    abstract::Elevation in plasma total homocysteine (tHcy) is believed to be causally related to cardiovascular disease. Like age and sex, the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR(C677T)) is an important nonmodifiable determinant of tHcy, which may be considered when describing normal ranges of tHcy i...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10239

    authors: Husemoen LL,Thomsen TF,Fenger M,Jørgensen HL,Jørgensen T

    更新日期:2003-05-01 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

  • Univariate analysis of dichotomous or ordinal data from twin pairs: a simulation study comparing structural equation modeling and logistic regression.

    abstract::The univariate analysis of categorical twin data can be performed using either structural equation modeling (SEM) or logistic regression. This paper presents a comparison between these two methods using a simulation study. Dichotomous and ordinal (three category) twin data are simulated under two different sample size...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1996)13:1<79::AID-GEPI7>3.

    authors: Ramakrishnan V,Meyer JM,Goldberg J,Henderson WG

    更新日期:1996-01-01 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

  • 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

    pub_type:

    doi:10.1002/1098-2272(200012)19:4<289::AID-GEPI2>3.0.C

    authors: Thomas DC

    更新日期:2000-12-01 00:00:00

  • Phenotype validation in electronic health records based genetic association studies.

    abstract::The linkage between electronic health records (EHRs) and genotype data makes it plausible to study the genetic susceptibility of a wide range of disease phenotypes. Despite that EHR-derived phenotype data are subjected to misclassification, it has been shown useful for discovering susceptible genes, particularly in th...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22080

    authors: Wang L,Damrauer SM,Zhang H,Zhang AX,Xiao R,Moore JH,Chen J

    更新日期:2017-12-01 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

    doi:10.1002/gepi.21645

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

    更新日期:2012-09-01 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

  • 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

  • Extensions to sib-pair linkage tests applicable to disorders characterized by delayed onset.

    abstract::Extensions of the approach to sib-pair linkage tests developed by Haseman and Elston [Behav Genet 2:3-19, 1972] are proposed which incorporate information on age of onset and age at examination. Alternate sources for the age of onset corrections are described, including models for the estimation of parameters associat...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370070607

    authors: Dawson DV,Kaplan EB,Elston RC

    更新日期:1990-01-01 00:00:00

  • Multifactorial disease risk calculator: Risk prediction for multifactorial disease pedigrees.

    abstract::Construction of multifactorial disease models from epidemiological findings and their application to disease pedigrees for risk prediction is nontrivial for all but the simplest of cases. Multifactorial Disease Risk Calculator is a web tool facilitating this. It provides a user-friendly interface, extending a reported...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22101

    authors: Campbell DD,Li Y,Sham PC

    更新日期:2018-03-01 00:00:00

  • Comparison of empirical strategies to maximize GENEHUNTER lod scores.

    abstract::We compare four strategies for finding the settings of genetic parameters that maximize the lod scores reported in GENEHUNTER 1.2. The four strategies are iterated complete factorial designs, iterated orthogonal Latin hypercubes, evolutionary operation, and numerical optimization. The genetic parameters that are set a...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370170718

    authors: Chen CH,Finch SJ,Mendell NR,Gordon D

    更新日期:1999-01-01 00:00:00

  • Analysis of bipolar disorder using affected relatives.

    abstract::We have analyzed the GAW10 data from several studies of bipolar affective disorder (BPAD) using the software packages SimIBD and SIMWALK2. SimIBD implements a simulation-based affected-pedigree-member (APM) statistic, called SimAPM, as well as an APM-like statistic, also called SimIBD, that measures identical-by-desce...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1997)14:6<605::AID-GEPI9>3

    authors: Davis S,Sobel E,Marinov M,Weeks DE

    更新日期:1997-01-01 00:00:00

  • Sib-pair linkage tests for disease susceptibility loci: common tests vs. the asymptotically most powerful test.

    abstract::Several statistical tests for linkage between a disease susceptibility locus and a marker locus for sib-pair data are examined analytically. Two common statistics, a test based on the mean number of marker alleles shared identical by descent by sib-pairs, and a test based on the proportion of sib-pairs sharing exactly...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370070506

    authors: Schaid DJ,Nick TG

    更新日期:1990-01-01 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

  • 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