Journal Article

Genetic Association Studies of Adult-Onset Diseases Using the Case-Spouse and Case-Offspring Designs

Wen-Chung Lee

in American Journal of Epidemiology

Published on behalf of Johns Hopkins Bloomberg School of Public Health

Volume 158, issue 11, pages 1023-1032
Published in print December 2003 | ISSN: 0002-9262
Published online December 2003 | e-ISSN: 1476-6256 | DOI:
Genetic Association Studies of Adult-Onset Diseases Using the Case-Spouse and Case-Offspring Designs

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Genetic studies of complex human diseases rely heavily on the family-based association paradigm. However, recruiting parents or siblings can be a difficult task in practice. The author proposes two alternatives, the case-spouse and the case-offspring designs, that are to be analyzed by the mating disequilibrium test. Two assumptions are required: 1) the marker genotype frequencies at conception should be the same for both sexes; and 2) there is no selective attrition of marker allele(s) through gestation and over time. Within this setting, the case-spouse and the case-offspring studies are valid designs, even if only one sex can get the disease, even if cases/spouses/offspring all have different risk factor profiles, and even under assortative mating. If the population is stratified and there is intermarriage between strata, one can type additional null markers across the genome for an admixture correction. The number of families required in a case-spouse design is almost identical to that in a case-parents design. For the case-offspring study with one offspring per family, the number of families should be doubled. Because of the ease in recruiting control subjects, the case-spouse and the case-offspring designs are viable alternatives for genetic association studies of adult-onset diseases.

Keywords: epidemiologic methods; genetics; polymorphism, single nucleotide; Abbreviations: df, degree of freedom; MDT, mating disequilibrium test; PDT, pedigree disequilibrium test; TDT, transmission/disequilibrium test.

Journal Article.  6407 words.  Illustrated.

Subjects: Public Health and Epidemiology

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