A follow-up linkage study supports evidence for a bipolar affective disorder locus on chromosome 21q22

Evidence for linkage between bipolar affective disorder (BP) and 21q22 was first reported by our group in a single large pedigree with a lod score of 3.41 with the PFKL locus, In a subsequent study, with denser marker coverag e in 40 multiplex BP pedigrees, we reported supporting evidence with a two- point lod score of 2.76 at the D21S1260 locus, about 6cM proximal to PFKL, For cost-efficiency, the individuals genotyped in that study comprised a su bset of our large pedigree sample. To augment our previous analysis, we now report a follow-up study including a larger sample set with an additional 331 typed individuals from the original 40 families, improved marker covera ge, and an additional 16 pedigrees, The analysis of all 56 pedigrees (a tot al of 862 genotyped individuals vs. the 372 genotyped previously), the larg est multigenerational BP pedigree sample reportedly analyzed to date, suppo rts our previous results, with a two-point lod score of 3.56 with D21S1260, The 16 new pedigrees analyzed separately gave a maximum two-point lod scor e of 1.89 at D21S266, less than 1 cM proximal to D21S1260, Our results are consistent with a putative BP locus on 21q22, (C) 2001 Wiley-Liss, Inc.