There is mounting evidence for the convergence of bipolar affective disorder linkage in broad chromosomal regions, though the evidence generally, is not striking. Our scan of chromosome 11 on 22 multiplex pedigrees yielded modest peaks of allele sharing. Because linkage methods lose power when common alleles underlie genetic risk, we performed family-based linkage disequilibrium (LD) analysis. GASSOC (GDOM and GREC) and sib_tdt under both stringent (ASM I) and broad (ASM II) phenotype classifications were used. The highest transmission distortion was displayed by two loci on 11q23: D11S4090 (ASM I: GDOM P = 0.0000067, sib_tdt P = 0.00017; ASM II: GDOM P = 0.000025, sib_tdt P = 0.000025) and D11S4464 (ASM I: GDOM P = 0.001, sib_tdt P = 0.0095; ASM II: GDOM P = 0.0013, sib_tdt P = 0.0007). Excess transmission of the second most common allele of D11S4090 was found (P = 0.000022). The signals at D11S4090 may reflect linkage alone, if so, they meet the proposed statistical criteria for significant pointwise linkage. This study illustrates the power of LD methods in uncovering a susceptibility region with weak hints of a locus obtained from linkage analysis, lending support for a gene for bipolar disorder on 11q23, and potentially refining its location.
|Original language||English (US)|
|Number of pages||1|
|Journal||American Journal of Medical Genetics - Neuropsychiatric Genetics|
|State||Published - Aug 7 2000|
ASJC Scopus subject areas
- Psychiatry and Mental health
- Cellular and Molecular Neuroscience