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


: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 data. SNPs in major genes 1 and 6 were analyzed using transmission disequilibrium testing (TDT) [Spielman et al., Am J Hum Genet 52:506-16, 1993], sibship disequilibrium testing (SDT) [Horvath and Laird, Am J Hum Genet 63:1886-97, 1998], family-based association testing (FBAT) [Horvath et al., Eur J Hum Genet 9:301-6, 2001], and a chi-square analysis of founders. TDT and SDT were applied in a sample of independent nuclear families, while FBAT was applied in extended pedigrees. SNPs and microsatellites were analyzed with dichotomous and quantitative trait definitions using FBAT in the isolate and outbred populations. The results of the TDT, SDT, and FBAT analyses are comparable using SNP data to identify the disease gene. However, these tests of association were not helpful in discriminating between functional and non-functional SNPs in disequilibrium. SNP data were able to identify association with affection status in a gene that influences the liability directly (MG6), but did not perform as well when assessing association with affection status in a gene that influences the outcome only through a quantitative trait (MG1). Association with MG1 was observed using the SNP data when the outcome was defined quantitatively. Microsatellite data were relatively unsuccessful in identifying association with the markers in the region of a major gene. The magnitude of the associations between SNPs and the dichotomous or quantitative trait definitions were similar in the outbred and isolated populations.


Genet Epidemiol


Genetic epidemiology


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




Has Abstract


2001-01-01 00:00:00








21 Suppl 1


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    pub_type: 杂志文章


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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Norris JM,Selinger-Leneman H,Génin E

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Carroll RJ,Gail MH,Benichou J,Pee D

    更新日期:2000-04-01 00:00:00

  • Pedigree disequilibrium tests for multilocus haplotypes.

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Dudbridge F

    更新日期:2003-09-01 00:00:00

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    更新日期:2012-09-01 00:00:00

  • The insulin gene and susceptibility to IDDM.

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    pub_type: 杂志文章


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  • Monte Carlo analysis on a large pedigree.

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


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

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

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


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

    更新日期:2001-01-01 00:00:00

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

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    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

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    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

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

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Becker T,Knapp M

    更新日期:2004-07-01 00:00:00

  • Testing the utility of mod scores and sib-pair analysis to detect presence of disease susceptibility loci.

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Neuman RJ,Xian H

    更新日期:1997-01-01 00:00:00

  • Logistic transmission modeling for the simulated data of GAW10 problem 2.

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Neas BR,Moser KL,Harley JB

    更新日期:1997-01-01 00:00:00

  • Comparison of two linkage inference procedures for genes related to the P300 component of the event related potential.

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Goldin LR,Chase GA

    更新日期:1999-01-01 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


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

    更新日期:1996-01-01 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


    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

  • Familial aggregation of breast cancer with early onset lung cancer.

    abstract::Site-specific familial aggregation and evidence supporting Mendelian codominant inheritance have been shown in lung cancer. In characterizing lung cancer families, a number of other cancers have been observed. The current study evaluates whether first-degree relatives of early onset lung cancer cases are at increased ...

    journal_title:Genetic epidemiology

    pub_type: 临床试验,杂志文章


    authors: Schwartz AG,Siegfried JM,Weiss L

    更新日期:1999-11-01 00:00:00

  • Analysis of multiple phenotypes.

    abstract::The complex etiology of common diseases like cardiovascular disease, diabetes, hypertension, and rheumatoid arthritis has led investigators to focus on the genetics of correlated phenotypes and risk factors. Joint analysis of multiple disease-related phenotypes may reveal genes of pleiotropic effect and increase analy...

    journal_title:Genetic epidemiology



    authors: Kent JW Jr

    更新日期:2009-01-01 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


    authors: Li X,Zhang S,Sha Q

    更新日期:2020-01-01 00:00:00

  • Robustness of the unified model to shared environmental effects in the analysis of dichotomous traits.

    abstract::Simulation studies were conducted to assess to what extent the conclusions of segregation analysis, performed under the unified model, can be affected by the presence of unmeasured environmental factors shared by family members. Dichotomous data were generated on six-member nuclear families under two variants of the m...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Demenais F,Abel L

    更新日期:1989-01-01 00:00:00

  • The role of environmental heterogeneity in meta-analysis of gene-environment interactions with quantitative traits.

    abstract::With challenges in data harmonization and environmental heterogeneity across various data sources, meta-analysis of gene-environment interaction studies can often involve subtle statistical issues. In this paper, we study the effect of environmental covariate heterogeneity (within and between cohorts) on two approache...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Li S,Mukherjee B,Taylor JM,Rice KM,Wen X,Rice JD,Stringham HM,Boehnke M

    更新日期:2014-07-01 00:00:00

  • To type or not to type: the use of unaffected siblings in nonparametric linkage analysis.

    abstract::Unaffected individuals are often disregarded in nonparametric linkage analysis. Because of the presumed high complexity of genetic interactions and the resulting low penetrance of any single genetic effect, the statistical contribution of unaffected sib pairs is thought to be considerably lower than that of the affect...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Majewski J

    更新日期:2001-01-01 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

  • Testing untyped alleles (TUNA)-applications to genome-wide association studies.

    abstract::The large number of tests performed in analyzing data from genome-wide association studies has a large impact on the power of detecting risk variants, and analytic strategies specifying the optimal set of hypotheses to be tested are necessary. We propose a genome-wide strategy that is based on one degree of freedom te...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Nicolae DL

    更新日期:2006-12-01 00:00:00

  • Genetic association with multiple traits in the presence of population stratification.

    abstract::Testing association between a genetic marker and multiple-dependent traits is a challenging task when both binary and quantitative traits are involved. The inverted regression model is a convenient method, in which the traits are treated as predictors although the genetic marker is an ordinal response. It is known tha...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Yan T,Li Q,Li Y,Li Z,Zheng G

    更新日期:2013-09-01 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


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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: König IR

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    abstract::Genome-wide association (GWA) studies have proved extremely successful in identifying novel genetic loci contributing effects to complex human diseases. In doing so, they have highlighted the fact that many potential loci of modest effect remain undetected, partly due to the need for samples consisting of many thousan...

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    更新日期:2010-05-01 00:00:00