SAGE Programs: Model-Free Linkage Analysis for Complex Cardiovascular Phenotypes

A complex disease trait refers to a phenotype that does not follow simple Mendelian segregation attributable to a single gene locus, but instead may be caused by multiple disease loci, their interactions, polygenic inheritance, and environmental effects. Most cardiovascular disorders are thought to have a polygenic basis with complex interactions with environmental factors. A gene that increases or decreases the risk to a complex cardiovascular disease (susceptibility gene) can now be mapped to a specific chromosomal region by model-free linkage analysis, and follow-up molecular genetic studies can identify the specific gene at the locus. This chapter describes a protocol for model-free linkage analysis of a complex trait, as implemented in the popular genetic analysis software—SAGE. In particular, the Haseman-Elston sib-pair regression method is introduced and implemented with examples to demonstrate how to identify susceptibility loci for complex traits.