Genome scans for susceptibility genes in bipolar affective disorder

A genome-wide scan for genetic linkage can suggest fresh insights into disease aetiology. However, in the case of complex disorders such as bipolar affective disorder (BPAD), the results of genome-wide scans must be interpreted with caution. We review 10 published and 10 in-progress genome scans of BPAD, encompassing 3536 affected individuals in 1119 pedigrees. We find that ascertainment methods vary widely, with no two studies using identical methods. Sample sizes and marker densities have generally been well below what is now considered adequate, but several in-progress studies are using larger samples and more closely spaced markers. Few findings reach the 'suggestive' threshold, and fewer still reach the 'significant' threshold at genome-wide levels of significance. Strategies for pooling samples or subjecting findings in different samples to meta-analysis are being developed, but differences in ascertainment methods may have a large impact on the uniformity of different samples and hamper efforts at combining data or findings. There is also a need for methods that help define more genetically homogeneous phenotypes, take into account interactions between multiple susceptibility loci, and accommodate additional complexity (eg parent-of-origin effects) in the search for linkage.