Abstract
Background
In 1989 the National Institute of Mental Health began a collaborative effort to identify
genes for bipolar disorder. The first 97 pedigrees showed evidence of linkage to chromosomes
1, 6, 7, 10, 16, and 22 (Nurnberger et al 1997). An additional 56 bipolar families
have been genotyped, and the combined sample of 153 pedigrees studied.
Methods
Three hierarchical affection status models were analyzed with 513 simple sequence
repeat markers; 298 were common across all pedigrees. The primary analysis was a nonparametric
genome-wide scan. We performed conditional analyses based on epistasis or heterogeneity
for five regions.
Results
One region, on 16p13, was significant at the genome-wide p < .05 level. Four additional chromosomal regions (20p12, 11p15, 6q24, and 10p12)
showed nominally significant linkage findings (p ≤ .01). Conditional analysis assuming epistasis identified a significant increase
in linkage at four regions. Families linked to 6q24 showed a significant increase
in nonparametric logarithms of the odds (NPL) scores at 5q11 and 7q21. Epistasis also
was observed between 20p12 and 13q21, and 16p13 and 9q21.
Conclusions
The findings are presented in rank order of nominal significance. Several of these
regions have been previously implicated in independent studies of either bipolar disorder
or schizophrenia. The strongest finding is at 16p13 at D16S748 with an NPL of 3.3,
there is evidence of epistasis between this locus and 9q21. Application of conditional
analyses is potentially useful in larger sample collections to identify susceptibility
genes of modest influence that may not be identified in a genome-wide scan aimed to
identify single gene effects.
Keywords
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Article info
Publication history
Accepted:
August 4,
2003
Received in revised form:
June 13,
2003
Received:
February 18,
2003
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
