Are linkage analysis and the collection of family data dead? Prospects for family studies in the age of genome-wide association.

International audienceThe HapMap project and the discovery of millions of single nucleotide polymorphisms (SNPs) throughout the human genome, together with the development of bead and chip technology, has made it feasible to type hundreds of thousands of markers on an individual for a few hundred dollars. Because of the extensive linkage disequilibrium (LD) that exists, genome-wide association studies are currently being conducted on samples of unrelated persons in the belief by some that this is now the design of choice to discover genetic variants underlying relatively common complex diseases. Huge tissue repositories have been set up for the purpose of conducting large-sample case-control studies. Should we therefore stop collecting family data, forget that we inherit our genes from our parents and ignore the fundamental laws of genetic transmission as being unnecessary for gene discovery? Can we hope to anticipate, understand and treat the many diseases to which humans are prone, simply by finding genomic locations that differ between those who have and those who do not have disease? Below we argue that, although they have a useful role to play, it should not be naively assumed that the time has come for genome-wide association studies to replace genome-wide linkage studies, or that the collection of family data is no longer necessary