The field of genetic epidemiology seeks to identify the genetic risk factors underlying human disease. First, one must assess whether the trait has an underlying genetic influence; this is done by estimating familial relative risk and conducting segregation analysis. In order to discover genes influencing human disease, both family- and population-based studies are designed, and linkage and association methods are used to analyse the relationship between the trait(s) of interest and genetic markers. A variety of approaches to both linkage and association analysis exist, each having strengths and weaknesses for differing situations. In general, linkage analysis is more powerful for detecting rare genes, whereas association analysis is more powerful for detecting common allelic effects that might be weaker. In addition, when studying complex traits, other issues must be considered, including interactions with other genes and the environment, parent-of-origin effects, as well as the effect of structural variants.

Key Concepts:

• Genetic epidemiologists design both family- and population-based studies to find genes influencing disease risk.
  
• Before conducting a gene mapping study, one must first ascertain whether the trait is influenced by genetic effects.
  
• Linkage and association analysis are two complementary methods used to analyse the relationship between trait(s) and genetic markers.
  
• The approach used (linkage versus association) depends on the study design, and these approaches depend on the genetic parameters (rare versus common, large versus small effects).
  
• Other factors – gene–gene interaction, gene–environment interaction, existence of structural variants and parent-of-origin effects – further complicate the search for disease genes.