AFFECTED-SIB-PAIR ANALYSES REVEAL SUPPORT OF PRIOR EVIDENCE FOR A SUSCEPTIBILITY LOCUS FOR BIPOLAR DISORDER, ON 21Q

In 22 multiplex pedigrees screened for linkage to bipolar disorder, by use of 18 markers on chromosome 21q, single-locus affected-sib-pair ( ASP) analysis detected a high proportion (57%-62%) of alleles shared i dentical by descent (IBD), with P values of .049-.0008 on nine marker loci. Multilocus ASP analyses revealed locus trios in the distal regio n between D21S270 and D21S171, with excess allele sharing (nominal P v alues <.01) under two affection-status models, ASM I (bipolars and sch izoaffectives) and ASM II (ASM I plus recurrent unipolars). In additio n, under ASM I, the proximal interval spanned by D21S1436 and D21S65 s howed locus trios with excess allele sharing (nominal P values of .03- .0003). These findings support prior evidence that a susceptibility lo cus for bipolar disorder is on 21q.