Am J Epidemiol 2003; 158:1023-1032.
Copyright © 2003 by the Johns
Hopkins Bloomberg School of Public Health
Special Article |
Genetic Association Studies of Adult-Onset Diseases Using the Case-Spouse and Case-Offspring Designs
From the Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan, Republic of China.
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.
epidemiologic methods; genetics; polymorphism, single nucleotide
Abbreviations: Abbreviations: df, degree of freedom; MDT, mating disequilibrium test; PDT, pedigree disequilibrium test; TDT, transmission/disequilibrium test.
CiteULike 
Connotea 
Del.icio.us What's this?
Related articles in Am. J. Epidemiol.:
- Invited Commentary: Making the Most of Genotype Asymmetries
- Clarice Weinberg
Am. J. Epidemiol. 2003 158: 1033-1035.[Extract] [FREE Full Text] - Lee Responds to "Making the Most of Genotype Asymmetries"
- Wen-Chung Lee
Am. J. Epidemiol. 2003 158: 1036-1038.[Extract] [FREE Full Text]
This article has been cited by other articles:
|
|
 |
|
  W.-C. Lee and C.-H. Chang Assessing effects of disease genes and gene-environment interactions: the case-spouse design and the counterfactual-control analysis. J Epidemiol Community Health, August 1, 2006; 60(8): 683 - 685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-C. Lee A DNA Pooling Strategy for Family-Based Association Studies Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 958 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Weinberg Invited Commentary: Making the Most of Genotype Asymmetries Am. J. Epidemiol., December 1, 2003; 158(11): 1033 - 1035. [Full Text] [PDF]
|
|
|
|
|
|
W.-C. Lee Lee Responds to "Making the Most of Genotype Asymmetries" Am. J. Epidemiol., December 1, 2003; 158(11): 1036 - 1038. [Full Text] [PDF]
|
|