Comparison of statistics for candidate-gene association studies using cases and parents

Daniel J. Schaid, Steve S. Sommer

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

Studies of association between candidate genes and disease can be designed to use cases with disease, and in place of nonrelated controls, their parents. The advantage of this design is the elimination of spurious differences due to ethnic differences between cases and nonrelated controls. However, several statistical methods of analysis have been proposed in the literature, and the choice of analysis is not always clear. We review some of the statistical methods currently developed and present two new statistical methods aimed at specific genetic hypotheses of dominance and recessivity of the candidate gene. These new methods can be more powerful than other current methods, as demonstrated by simulations. The basis of these new statistical methods is a likelihood approach. The advantage of the likelihood framework is that regression models can be developed to assess genotype-environment interactions, as well as the relative contribution that alleles at the candidate-gene locus make to the relative risk (RR) of disease. This latter development allows testing of (1) whether interactions between alleles exist, on the scale of log RR, and (2) whether alleles originating from the mother or father of a case impart different risks, i.e., genomic imprinting.

Original languageEnglish (US)
Pages (from-to)402-409
Number of pages8
JournalAmerican journal of human genetics
Volume55
Issue number2
StatePublished - Aug 11 1994

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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