Study Report
Basic Info
| Reference |
Lopez de Lara, C.,2010 PMID: 20667171
|
| Citation |
Lopez de Lara, C., I. Jaitovich-Groisman, et al. (2010). "Implication of synapse-related genes in bipolar disorder by linkage and gene expression analyses." Int J Neuropsychopharmacol 13(10): 1397-1410.
|
| Disease Type |
Bipolar Disorder |
| Study Design |
family-based |
| Study Type |
Genome-wide linkage study |
| Sample Size |
36 families (275 genotyped individuals, 132 affected) |
| SNP/Region/Marker Size |
811 microsatellite markers for whole genome wide |
| Predominant Ethnicity |
Caucasian |
| Population |
Canadian |
| Gender |
36 probands:19 males and 17 females |
| Age Group |
Adults
:
mean age (S.D.) was 46.0(13.6) yr, and their mean age at onset was 24.5(7.9) yr.
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Detail Info
| Sample Diagnosis |
DSM and RDC |
| Sample Status |
A total of 36 probands were recruited from specialized clinics at McMaster University, Hamilton; University of Ottawa; and Dalhousie University, Halifax. They all met criteria for bipolar I (n=25) or bipolar II (n=11).None of the probands had any other Axis I or Axis II disorders.Their clinical course had been characterized by a high number of manic and depressive episodes before lithium (8.2,SD=10.1) and by a full stability on lithium monotherapy for 14.4,SD=6.8 yr on average.participants were aged >=16 yr at the time of recruitment. Overall, 36 multiplex families were included, accounting for a total of 275 individuals. Of these, 132 were considered affected. |
| Technique |
genotyping |
| Statistical Method |
Linkage was tested by two-point LOD score analysis,with genetic models based on our previous analyses of mode of inheritance in this population (Alda et al. 1997). We used the MLINK program from the FASTLINK computer package (Cottingham et al.1993). |
| Result Summary |
We identified regions 3p25, 3p14 and 14q11 as showing the highest genome-wide linkage signal (LOD 2.53, 2.04 and 3.19, respectively). Fine mapping provided further support for 3p25, while only modest support was found in the other two regions. We identified a group of synaptic, mitochondrial and apoptotic genes with altered expression patterns in BD. Analysis of an independent microarray dataset supported the implication of synapse-related and mitochondrial genes in BD. In conclusion, using two complementary strategies, we found evidence of linkage to lithium-responsive BD on 3p25, 3p14 and 14q11 as well as significantly dysregulated genes on these regions suggesting altered synaptic and mitochondrial function in BD. Further studies are warranted to demonstrate the functional role of these genes in BD. |
Regions reported by this study for BD (count: 5)
| Region |
Statistical Values |
Author Comments |
Result Category |
| 14q11.2 |
two-point LOD score analysis: model REC2, LOD score = 3.19, P-value = 0.0001
|
Suggestive linkage was found in this region.
Suggestive linkage was found in this region.
|
Trend
|
| 3p14.1 |
two-point LOD score analysis: model DOM2, LOD score = 2.04, P-value = 0.0012
|
Suggestive linkage was found in this region.
Suggestive linkage was found in this region.
|
Trend
|
| 3p25.1 |
two-point LOD score analysis: model INTER, LOD score = 2.53, P-value = 0.0003
|
Suggestive linkage was found in this region.
Suggestive linkage was found in this region.
|
Trend
|
| 17q12 |
two-point LOD score analysis: model REC1, LOD score = 1.94, P-value = 0.0013
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Suggestive linkage was found in this region.
Suggestive linkage was found in this region.
|
Trend
|
| 21q21.1 |
two-point LOD score analysis: model REC1, LOD score = 1.91, P-value = 0.0021
|
Suggestive linkage was found in this region.
Suggestive linkage was found in this region.
|
Trend
|
