Search for bipolar disorder susceptibility loci: the application of a modified genome scan concentrating on gene-rich regions

Conducting genome wide screens for evidence of genetic linkage has become a well-established method for identifying regions of the human genome harboring susceptibility loci for complex disorders. For bipolar disorder, a number of such studies have been performed, and several regions of the genome have potentially been implicated in the disorder. The classic design for a genome screen involves examining polymorphic genetic markers spaced at regular intervals throughout the genome, typically every 10 cM, for evidence of linkage. An alternative design, based on the observation that genes do not appear to be evenly distributed, was proposed, enabling the number of markers examined in a genome wide screen to be reduced. This article describes the application of such a modified screen to a collection of 48 Irish families with bipolar disorder, comprising a total of 82 affected sib-pairs. From the results obtained a number of regions are highlighted for further study. One of these regions (17q11.1-q12) coincides with the location of a candidate gene, the serotonin transporter, whereas others concur with the findings of published studies. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:728-732, 2000.