Relative risks and effective number of meioses: A unified approach for general genetic models and phenotypes

Azra Kurbasic, O Hossjer

Research output: Contribution to journalArticlepeer-review

Abstract

Many common diseases are known to have genetic components, but since they are non-Mendelian, i.e. a large number of genetic factors affect the phenotype, these components are difficult to localize. These traits are often called complex and analysis of siblings is a valuable tool for mapping them. It has been shown that the power of the affected relative pairs method to detect linkage of a disease susceptibility locus depends on the locus contribution to increased risk of relatives compared with population prevalence Risch, 1990a,b). In this paper we generalize calculation of relative risk to arbitrary phenotypes and genetic models, but also show that the relative risk can be split into the relative risk at the main locus and the relative risk due to interaction between the main locus and loci at other chromosomes. We demonstrate how the main locus contribution to the relative risk is related to probabilities of allele sharing identical by descent at the main locus, as well as power to detect linkage. To this end we use the effective number of meioses, introduced by Hossjer (2005a) as a convenient tool. Relative risks and effective number of meioses are computed for several genetic models with binary or quantitative phenotypes, with or without polygenic effects.
Original languageEnglish
Pages (from-to)907-922
JournalAnnals of Human Genetics
Volume70
Issue number6
DOIs
Publication statusPublished - 2006

Subject classification (UKÄ)

  • Probability Theory and Statistics

Keywords

  • linkage analysis
  • complex diseases
  • relative risk
  • effective number of
  • meioses

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