Abstract
Bipolar disorder (BP) is a highly heritable, common, severe mood
disorder with lifetime prevalence up to 4%. We conducted a 10 cM
genome scan on 35 multigenerational pedigrees with 288 genotyped
individuals and identified linkage to chromosome 15q25-26. Using a
broad disease definition including individuals diagnosed with BPI,
schizoaffective disorder mania type, BPII or recurrent unipolar
depression, 130 individuals in the cohort were affected. We found a
maximumtwo pointLODscore of 3.85 and a maximummultipointLOD
score of 4.76 at D15S130 using 60% age-specific penetrance, the
dominant model under broad disease definition. Markers on chromosomes
4q, 6q, and 13q suggested linkage, in addition to a second marker
adjacent to D15S130. The region on 15q25-26 was further investigated
by typing 8 additional microsatellite markers, yielding significant
scores with a maximum two point LOD score of 4.66 and a maximum
multipoint LOD score of 5.17 at marker D15S1004. A 95% confidence
interval calculated by the Zmax-1 method suggests a support interval
spanning 17 cM between markers D15S979 and D15S816 (86.6-
92.8 Mb). Haplotype analysis based on pedigree-specific, identicalby-
descent, allele sharing supported the 95% confidence interval
estimates. The 15q25-26 locus is supported by linkage findings from
studies on recurrent early-onset major depressive disorder, BP with
psychotic features and a study of schizophrenic and BP subjects,
suggesting that the locusmight contain a gene conferring susceptibility
to both mood and psychotic disorder.
disorder with lifetime prevalence up to 4%. We conducted a 10 cM
genome scan on 35 multigenerational pedigrees with 288 genotyped
individuals and identified linkage to chromosome 15q25-26. Using a
broad disease definition including individuals diagnosed with BPI,
schizoaffective disorder mania type, BPII or recurrent unipolar
depression, 130 individuals in the cohort were affected. We found a
maximumtwo pointLODscore of 3.85 and a maximummultipointLOD
score of 4.76 at D15S130 using 60% age-specific penetrance, the
dominant model under broad disease definition. Markers on chromosomes
4q, 6q, and 13q suggested linkage, in addition to a second marker
adjacent to D15S130. The region on 15q25-26 was further investigated
by typing 8 additional microsatellite markers, yielding significant
scores with a maximum two point LOD score of 4.66 and a maximum
multipoint LOD score of 5.17 at marker D15S1004. A 95% confidence
interval calculated by the Zmax-1 method suggests a support interval
spanning 17 cM between markers D15S979 and D15S816 (86.6-
92.8 Mb). Haplotype analysis based on pedigree-specific, identicalby-
descent, allele sharing supported the 95% confidence interval
estimates. The 15q25-26 locus is supported by linkage findings from
studies on recurrent early-onset major depressive disorder, BP with
psychotic features and a study of schizophrenic and BP subjects,
suggesting that the locusmight contain a gene conferring susceptibility
to both mood and psychotic disorder.
| Original language | English |
|---|---|
| Article number | O2.3 |
| Pages (from-to) | 695-696 |
| Number of pages | 2 |
| Journal | American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics |
| Volume | 141B |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 5 Oct 2006 |
| Event | 14th World Congress on Psychiatric Genetics - Cagliari, Italy Duration: 28 Oct 2006 → 1 Nov 2006 |