Linkage versus Association Studies

Doctor Anil Malhotra compares (older) linkage and (more modern) association techniques for identifying candidate genes for disorders.

Linkage analysis was a very popular method for detecting genes of major effect particularly in psychiatry. It was used mostly in the '80s and perhaps early 1990s usually based on within-family design either sibling pairs or large multiplex pedigrees. As I said, it is really optimally designed for disorders in which their genes have major effect. One of the things I think that came out of that generation of linkage studies was [that] it is relatively clear that if there are genes of major effect they are relatively rare and relatively isolated populations within schizophrenia. Association studies take the opposite approach. In general, there are case-control association studies, though there are family-based approaches also, which hopefully are going to find genes that have less of a strong effect and thus maybe multiple genes of lesser effect can be detected. With the association approach, where we essentially compare allele frequencies between cases and controls and then examine whatever number of genes or number of polymorphisms in individual study.