Evidence of a susceptibility locus for bipolar disorder on chromosome 1p in the Sardinian population

Introduction: Twin, family segregation and adoption studies clearly indicate that Bipolar Disorder (BD) presents a strong genetic component. However, the inheritance of BD is characterized by complex patterns due to heterogeneity, polygenicity and interaction of environmental factors. Albeit no gene has been clearly identified for BD, linkage studies have recurrently sorted out several chromosomal regions. The discovery of genetic factors implicated in the predisposition to BD may greatly profit from genetic studies in isolated populations with lesser genetic heterogeneity and probably fewer environmental differences than outbred populations. Methods: We performed a genome-wide scan using 506 microsatellite polymorphic markers with an average interval size of 7.6 cM on a sample of 88 nuclear families with at least two affected sibs with BP recruited in theSardinian population. Results: Evidence for linkage wasobserved at two markers (NPL¼3.44 P value¼0.00028 and NPL¼3.45 P value¼0.00027) in the 1p chromosomal region. A subsequent fine mapping of 29 cM in the region using the same set of families and 21 new polymorphic microsatellite markers, spaced at 1.2 cMonaverage, confirmed the linkage result.NPL values greater than 3 or comprised between 2.5 and 3 were obtained for two and nine, respectively, of the additional markers. Conclusions: These results implicate a new chromosomal region in the genetic susceptibility to BP. Further genetic investigation of this locus in Sardinian or other populations may allow a more rapid discovery of genetic variations predisposing to BP.