A Genome-wide Search for Chromosomal Loci Linked to Bipolar
Affective Disorder in the Old Order Amish
Edward I. Ginns, Jurg Ott, Janice A. Egeland, Cleona R. Allen,
Cathy S.J. Fann, David L. Pauls, Jean Weissenbach, John P. Carulli,
Kathleen M. Falls, Tim P. Keith & Steven M. Paul
Nature Genetics , 12(4), 431-435 (1996)
Abstract
The most characteristic features of bipolar affective disorder (manic-depressive
illness) are episodes of mania (bipolar I, BPI) or hypomania (bipolar II, BPII)
interspersed with periods of depression. Manic-depressive illness afflicts about
one percent of the population, and if untreated, is associated with an approximately
20% risk of suicide. Twin, family and adoption studies provide compelling
evidence for a partial genetic aetiology, but the mode(s) of inheritance has not
been identified. Nonetheless, the majority of genetic linkage studies have assumed
classical mendelian inheritance attributable to a single major gene. Although
segregation analyses have yielded inconsistent results (with most studies rejecting
a single locus inheritance model), the best single gene model is dominant inheritance
if only BPI is considered. Reported linkages of bipolar affective disorder on chromosomes
11, 18, 21 and X have been difficult to substantiate, and additional studies are
required for replication or exclusion of these regions. We now present the
results of our genome-wide linkage analyses that provide evidence that regions on
chromosomes 6, 13 and 15 harbour susceptibility loci for bipolar affective disorder,
suggesting that bipolar affective disorder in the Old Order Amish is inherited as a
complex trait.
