Further analyses of the NIMH bipolar dataset: Follow up on suggestive linkage results on 1p and 10p

Bipolar Affective Disorder (BP) is complex and familial. However, the genetics of BP is not consistent with a major locus inheritance. Linkage of BP has been reported in several chromosomal regions. Data from 540 subjects from 97 families in wave one of a four site collaborative study supported as part of the NIMH genetics initiative indicated possible linkage to a region on chromosome 1 near D1S224 (MOD 1.66, p<0.001) as well as regions on chromosome 10 near D10S1423 (MOD 3.40, p<0.001) and D10S188 (MOD 3.47, p<0.001). Ascertainment required a subject affected with Bipolar I disorder (BP1) and another subject with BP1 or schizoaffective disorder, bipolar type (SA/BP). Subjects were considered affected if diagnosed with BP1, SA/BP, or Bipolar II disorder (BP2). Additional markers were then genotyped in a 20cm region around D1S224. With these new markers and additional genotyping of 353 individuals from 56 families in wave 2 of the study, there is no longer suggestive evidence for linkage to D1S224. Using Mapmaker/Sibs, a multipoint analysis using the all pairs unweighted option yields a maximal lod score of 0.96 near D1S224. Evidence for linkage on 10p remains strong with an all pairs unweighted lod score of 4.48 near D10S1423.