Searching for genes

statisticians and geneticists have developed a new strategy for surveying the human genome in order to identify those genes involved in human disease.

Finding the gene loci involved in particular human diseases (that is, the places along the human genome where those genes are located) has proved remarkably difficult.

Almost all current methods of searching look separately at different positions in the human genome where disease-related variants might be (there are hundreds of thousands, or millions, of such positions). However, it is known that it is often the interaction of genes at different points on the genome which causes disease, and so just looking at individual gene loci might not be very effective.

However, checking each possible pair of loci involves many more tests: if a study examines 300,000 variants, there are about 45,000,000,000 possible interacting pairs.

This raises practical and statistical problems – the latter because if such an enormous number of hypotheses are tested, the chance of a false positive result is very high. This multiple testing problem requires that each individual test must be very tightly controlled, and has led to a widespread view that searching for interacting genes would not be feasible.