Absence of a significant linkage between Na+,K+-ATPase suburmit (ATP1A3 and ATP1B3) genotypes and bipolar affective disorder in the old-order Amish

Previous studies provide evidence for a genetic component for susceptibilit y to bipolar affective disorder (BPAD) in the old-order Amish population. E l-Mallakh and Wyatt [1995: Biol Psychiatry 37:235-244] have suggested that the Na+,K+-ATPase may be a candidate gene for BPAD, This study examines the relationship between BPAD in the old-order Amish cohort and the Na+,K+-ATP ase alpha1 and beta3 subunit genes (ATP1A3, ATP1B3). A total of 166 sibling pairs were analyzed for linkage via nonparametric methods, Suggestive leve ls of statistical significance were not reached in any stratification model for affective illness, Overall, the results do not support linkage of bipo lar disorder to the Na+,K+-ATPase alpha subunit gene (ATP1A3) and beta subu nit gene (ATP1B3) in these old-order Amish families and they show that thes e Na+,K+-ATPase subunit genes are not major effect genes (greater than or e qual to fourfold increased genetic risk of disease) for BPAD in the old-ord er Amish pedigrees. We cannot exclude other genetic variants of the Na+,K+- ATPase hypothesis for BPAD, whereby other loci may modifying Na+,K+-ATPase activity, (C) 2001 Wiley-Liss, Inc.