Linkage studies agnostically scanned the mapped genome by looking for chromosomal regions that were shared among affected family members (suggesting there was a gene in that region that contributed to the disorder). The advantage of linkage was that it did not require any a priori knowledge of the underlying biology of the outcome, in theory making it possible to discover new genes involved in the outcome that could expand our understanding of the biology of the disorder. Linkage studies were used to successfully identify many genes that contributed to Mendelian disorders, where a single gene following a straightforward inheritance pattern with a major impact on outcome was present (Gusella et al., 1983; Murray et al., 1982; Tsui et al., 1985). However, linkage methods were less successful when applied to complex behavioral outcomes where many genes are likely to be involved, each having just a small effect on the behavior, along with the environment.
