Combining Case-Control and Case-Trio Data From the Same Population in Genetic Association Analyses: Overview of Approaches and Illustration With a Candidate Gene Study

• Published in: American journal of epidemiology Vol. 170; no. 5; pp. 657 - 664
• Main Authors: Infante-Rivard, Claire, Mirea, Lucia, Bull, Shelley B.
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 01.09.2009; Oxford Publishing Limited (England)
• Subjects: Analysis. Health state; association; Biological and medical sciences; Case studies; Case-Control Studies; Epidemiology; General aspects; genetic; Genetic disorders; Genetic Variation - genetics; Genome-Wide Association Study - methods; Genotype; Genotype & phenotype; Humans; Leukemia; linkage disequilibrium; Medical sciences; Miscellaneous; Models, Genetic; nuclear family; Offspring; polymorphism; Population genetics; Population structure; Public health. Hygiene; Public health. Hygiene-occupational medicine; Research methodology; Statistical methods; statistical models; nuclear family; statistical models; association; polymorphism, genetic; models, genetic; case-control studies; genotype; linkage disequilibrium; Human; genetic; models; Typing; Family study; Genotype; Review; Case control study; Epidemiology; Population genetics; Nuclear family; Association; Gene; Statistical model; Typology; Public health; Polymorphism
• ISSN: 0002-9262; 1476-6256; 1476-6256
• DOI: 10.1093/aje/kwp180

In genetic association studies, investigators compare allele or genotype frequencies in unrelated case and control subjects or examine preferential allele transmissions from parents to affected offspring. In many genetic case-control studies, the collection of DNA material extends to relatives such as parents of cases. Thus, case-control and case-parent trio association analyses are possible. Whereas the goal of collecting genetic information from family members in a study initially designed as a case-control study is to enrich the genetic analysis, increase power, or address concern about population structure bias, methods of combining genetic data from unrelated case and control subjects with genetic trio data from the same study population are not well known. A number of hybrid approaches have been developed that utilize such data together. In this paper, the authors describe key features of genetic case-control and case-parent trio studies and review commonly used methods of genetic analysis for case-parent trio designs. In addition, they provide a pragmatic review of statistical methods and available software for existing hybrid approaches that combine various components of case-control and genetic trio data. The application of all methods is illustrated using a candidate gene study of childhood leukemia that included case-control subjects and their parents.