Study Report
Basic Info
| Reference |
Kremeyer,B.,2010 PMID: 21071953
|
| Citation |
Kremeyer, B., J. Garcia, et al. (2010). "Genome-wide linkage scan of bipolar disorder in a Colombian population isolate replicates Loci on chromosomes 7p21-22, 1p31, 16p12 and 21q21-22 and identifies a novel locus on chromosome 12q." Hum Hered 70(4): 255-268.
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| Disease Type |
Bipolar Disorder |
| Study Design |
pedigree |
| Study Type |
Genome-wide linkage study |
| Sample Size |
Fifteen extended pedigrees comprised 90 cases of BPI, 22 cases of major depression, and 1 case each of schizophrenia and BPII |
| SNP/Region/Marker Size |
382 microsatellite markers for whole genome wide |
| Predominant Ethnicity |
|
| Population |
Colombian |
| Gender |
BPI (37.8% males, 62.2% females), 22 cases of major depression (18.2% males, 82.8% females), and 1 case each of schizophrenia (female) and BPII (male) |
| Age Group |
Adults
:
BPI (age at onset 22.2,SD=7.6 years), 22 cases of major depression (age at onset 26.6,SD=13.8 years), and 1 case each of schizophrenia (age at onset 27 years) and BPII (age at onset could not be determined reliably)
|
Detail Info
| Sample Diagnosis |
DSM |
| Sample Status |
Fifteen extended pedigrees segregating severe BP were collected as part of an ongoing psychiatric genetics programme in the population isolate of Antioquia, Colombia. Six of these had been included in a previous linkage scan (CO3, CO4, CO7, CO14, CO18, CO27) . Index cases were recruited in the municipalities of Medellin and Envigado (Antioquia, Colombia) at the Hospital Mental de Antioquia, the Hospital San Vicente de Paul, the Clinica Samean, the Clinica Insam, and the Mental Health Centre of Envigado. All index cases had at least 6 greatgrandparents born in Antioquia. Families with at least 3 individuals with a clinical diagnosis of BP were chosen for pedigree extension by a social worker or psychiatric nurse using the Family Interview for Genetic Studies. Family CO24 includes only 2 cases of BP; it was studied because it also includes 1 case of major depression and 1 case of schizophrenia, which are phenotypes also considered in the analyses (see below). Family members were assessed by a psychiatrist using the Spanish version of the Diagnostic Interview for Genetic Studies (DIGS version 3) that we validated in Colombia. Final DSM-IV-TR diagnoses were reached through consensus between 2 expert psychiatrists in a best estimate procedure, as described by Freimer and colleagues. The occurrence of psychotic episodes was determined based on both the DIGS and medical records. Family members with a clinical diagnosis of BPI who were unavailable for interview (including deceased individuals) were considered affected if they had undergone at least 2 hospitalizations and clinical records allowed confirmation of symptoms through the best estimate process. No psychiatric diagnoses other than BPI were considered in family members that were unavailable for interview. In order to maintain a strict phenotypic definition, and to rule out cases where psychiatric symptoms might be secondary to other medical conditions, any psychiatric diagnoses in patients with mental retardation and/or neurological lesions, as well as cases related to substance abuse, were disregarded for the analyses. A total of 46 individuals (30.4% males, 69.6% females) had suffered from psychosis, operationally defined by the occurrence of at least 1 episode of hallucinations and/ or delusions. These included 43 of the 90 BPI cases (47.8%), the schizophrenic individual and 2 individuals with a psychotic mood disorder that did not meet the full diagnostic criteria for BP (these 2 individuals are included in families CO14 and CO15). |
| Technique |
genotyping |
| Statistical Method |
Multipoint parametric heterogeneity LOD (HLOD) score and nonparametric linkage (NPL) analyses were performed using SimWalk2 v2.9.1. |
| Result Summary |
RESULTS AND CONCLUSION: For BPI only, the most interesting result was obtained for chromosome 7p21.1-p22.2 under a recessive model of inheritance (heterogeneity LOD score = 2.80), a region that had previously been linked to BP in a study on Portuguese Island families. For both BPI and mood disorders, nonparametric analyses identified a locus on chromosome 12ct-q14 (nonparametric linkage = 2.55 and 2.35, respectively). This locus has not previously been reported as a candidate region for BP. Additional candidate regions were found on chromosomes 1p22-31 (mood disorders) and 21q21-22 (BPI), 2 loci that have repeatedly been implicated in BP susceptibility. Linkage analysis of psychosis as a phenotype identified candidate regions on chromosomes 2q24-31 and 16p12-q12. The finding on chromosome 16p is noteworthy because the same locus has been implicated by genome-wide association analyses of BP. |
Regions reported by this study for BD (count: 5)
| Region |
Statistical Values |
Author Comments |
Result Category |
| 21q21.1-q22.13 |
Parametric analysis, narrow, dominant model: Maximum HLOD = 2.14
|
Suggestive linkage was found in this region.
Suggestive linkage was found in this region.
|
Trend
|
| 1q24.2-q25.1 |
Parametric analysis, narrow, recessive model: Maximum HLOD = 1.47
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No significant linkage was found in this region.
No significant linkage was found in this region.
|
Negative
|
| 1p31.1-p22.1 |
Parametric analysis, narrow, dominant model: Maximum HLOD = 1.32
|
No significant linkage was found in this region.
No significant linkage was found in this region.
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Negative
|
| 13q33.1-q33.3 |
Parametric analysis, narrow, dominant model: Maximum HLOD = 1.46
|
No significant linkage was found in this region.
No significant linkage was found in this region.
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Negative
|
| 7p22.2-p21.1 |
Parametric analysis, narrow, recessive model: Maximum HLOD = 2.8
|
Suggestive linkage was found in this region.
Suggestive linkage was found in this region.
|
Trend
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