Score tests for familial correlation in genotyped-proband designs.


:In the genotyped-proband design, a proband is selected based on an observed phenotype, the genotype of the proband is observed, and then the phenotypes of all first-degree relatives are obtained. The genotypes of these first-degree relatives are not observed. Gail et al. [(1999) Genet Epidemiol] discuss likelihood analysis of this design under the assumption that the phenotypes are conditionally independent of one another given the observed and unobserved genotypes. Li and Thompson [(1997) Biometrics 53:282-293] give an example where this assumption is suspect, thus suggesting that it is important to develop tests for conditional independence. In this paper, we develop a score test for the conditional independence assumption in models that might include covariates or observation of genotypes for some of the first degree relatives. The problem can be cast more generally as one of score testing in the presence of missing covariates. A standard analysis would require specifying a distribution for the covariates, which is not convenient and could lead to a lack of model-robustness. We show that by considering a natural conditional likelihood, and basing the score test on it, a simple analysis results. The methods are applied to a study of the penetrance for breast cancer of BRCA1 and BRCA2 mutations among Ashkenazi Jews.


Genet Epidemiol


Genetic epidemiology


Carroll RJ,Gail MH,Benichou J,Pee D




Has Abstract


2000-04-01 00:00:00














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    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

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    authors: Moro-Furlani AM,Krieger H

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    journal_title:Genetic epidemiology

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    authors: Khoury MJ,Flanders WD,Lipton RB,Dorman JS

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    pub_type: 临床试验,杂志文章,随机对照试验


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

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    journal_title:Genetic epidemiology

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    authors: Lunn DJ,Whittaker JC,Best N

    更新日期:2006-04-01 00:00:00

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    authors: Deng HW,Li J,Recker RR

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    更新日期:2015-07-01 00:00:00

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    authors: Mensah-Ablorh A,Lindstrom S,Haiman CA,Henderson BE,Marchand LL,Lee S,Stram DO,Eliassen AH,Price A,Kraft P

    更新日期:2016-01-01 00:00:00

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    pub_type: 杂志文章


    authors: Lin JA,Zhu H,Knickmeyer R,Styner M,Gilmore J,Ibrahim JG

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    journal_title:Genetic epidemiology

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Hemminki K,Lönnstedt I,Vaittinen P,Lichtenstein P

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    journal_title:Genetic epidemiology

    pub_type: 杂志文章


    authors: Shin J,Corey M

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    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...

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    pub_type: 杂志文章


    authors: Hoffmann TJ,Lange C,Vansteelandt S,Laird NM

    更新日期:2009-12-01 00:00:00

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

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    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