ABSTRACT

This chapter focuses on how one might find the candidate genetic variants underlying complex traits. The history and rapid progress of human genetics has largely consisted of the application of Mendelian genetics to identify rare allelic variants with large phenotypic effects. Single nucleotide polymorphisms are both the most common and extensively surveyed form of genetic variation. There are several genetic features that allow relatively easy mapping of Mendelian traits. The sites contributing to variation in these traits are generally rare missense mutations that are in linkage disequilibrium with other surrounding sites. Diagnosis and phenotype characterization of neuropsychiatric traits is simply harder than diagnosis of, say, cystic fibrosis. The genetic variants leading to the disease will simply be different in distinct families. Neuropsychiatric traits are complex, and as such, are more difficult to analyze than most single-gene Mendelian traits. Nevertheless, the genetics research program has hope.