Genome scans for susceptibility genes in bipolar affective disorder

A genome-wide scan for genetic linkage can suggest fresh insights into dise ase aetiology, However, in the case of complex disorders such as bipolar af fective disorder (BPAD), the results of genome-wide scans must be interpret ed with caution. We review 10 published and 10 in-progress genome scans of BPAD, encompassing 3536 affected individuals in 1119 pedigrees, We find tha t ascertainment methods vary widely, with no two studies using identical me thods. Sample sizes and marker densities have generally been well below wha t is now considered adequate, but several in-progress studies are using lar ger samples and more closely spaced markers. Few findings I each the 'sugge stive' threshold, and fewer still reach the 'significant' threshold at geno me-wide levels of significance. Strategies for pooling samples or subjectin g findings in different samples to meta-analysis are being developed, but d ifferences in ascertainment methods may have a large impact on the uniformi ty of different samples and hamper efforts at combining data or findings. T here is also a need for methods that help define more genetically homogeneo us phenotypes, take into account interactions between multiple susceptibili ty loci, and accommodate additional complexity leg parent-of-origin effects ) in the search far linkage.