A new susceptibility locus for bipolar affective disorder in PAR1 on Xp22.3/Yp11.3

We present the findings of a linkage study of bipolar affective disorder (BPAD) that involve the pseudoautosomal region 1 of the human sex chromosomes. We analyzed a substantial subset of pedigrees (89 families of German and Spanish origin; 661 participants; 298 affected individuals) from the large collection of BPAD-affected families with which a genomewide linkage analysis was previously performed and where the pseudoautosomal regions were poorly covered. Nonparametric linkage (Z(lr)) scores were calculated. The highest Z(lr) scores were obtained on Xp22.3/Yp11.3 in the Spanish subsample (DXS1071; Z(lr) = 3.54, P(empirical) = 0.0009 for the broad definition of affection sttuts; Z(lr) = 2.63, P(empirical) = 0.0129 for the medium definition of affection status; Z(lr) = 2.12, P(empirical) = 0.0429 for the narrow definition of affection status). Empirical P-values are adjusted using the Bonferroni correction to account for the testing of three affection status definitions. This region has not drawn much attention in previous linkage studies of BPAD. On the basis of these results, Xp22.3/Yp11.3 should now be considered a candidate region for BPAD.