Linkage disequilibrium analysis of G-olfα (GNAL) in bipolar affective disorder

✍ Scribed by Tsiouris, S. J.; Breschel, T. S.; Xu, J.; McInnis, M. G.; McMahon, F. J.

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 386 KB
• Volume: 67
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/(sici)1096-8628(19960920)67:5<491::aid-ajmg11>3.0.co;2-i

✦ Synopsis

This study examines G-olf, as a possible candidate gene for susceptibility to bipolar affective disorder (BPAD) using the Transmission Disequilibrium Test (TDT). G-olf,, which encodes a subunit of a G-protein involved in intracellular signaling, maps within a region of chromosome 18 that has been implicated by two different linkage studies as a potential site of BPAD susceptibility loci. The expression pattern of G-olf, in the brain, its coupling to dopamine receptors, and the effects of lithium salts on G-proteins all support G-olf, as a candidate gene for BPAD. Our study population consisted of 106 probands and sibs with bipolar I disorder, with a median age-at-onset of 21.5 years ascertained from the United States. There was no evidence of linkage disequilibrium between BPAD and any of the observed G-olf, alleles in our sample. Division of families based on sex of the transmitting parent did not significantly change the results. This sample had good power (78%) to detect linkage disequilibrium with alleles conferring a relative risk equal to that estimated for the putative 18p locus (2.58). Our results do not support a major role for G-olf,as a susceptibility locus for BPAD in a substantial portion of our sample. Other genes lying near G-olf, within the linked region on chromosome 18 cannot be excluded by our data. This study illustrates the use of the TDT in evaluating candidate genes within linked chromosome regions.