Association study of schizophrenia with polymorphisms at six candidate genes

Virgos, Carmen; Martorell, Lourdes; Valero, Joaquı́n; Civeira, Fernando; Joven, Jorge; Labad, Antonio; Vilella, Elisabet; Figuera, Lı́dia

doi:10.1016/s0920-9964(00)00106-7

Cited by 104 publications

(44 citation statements)

References 36 publications

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“…[46][47][48][49][50] Although several association studies have been conducted to investigate the association of NTF3 and GRIN2B with schizophrenia and alcohol dependence, the results have been inconclusive. [51][52][53][54] Regarding potential candidate genes from other regions, we will not discuss these in the present report because (1) they have been reported previously for possible association with nicotine and/or alcohol dependence in independent sample; (2) potential candidate genes for a few chromosomal regions were discussed in our recent report based on the AA sample; 20 and/or (3) a limited number of candidate genes are obvious on the basis of their functionality unless we are able to demonstrate their association experimentally, a consideration which is well beyond the scope of this report.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide linkage scan for nicotine dependence in European Americans and its converging results with African Americans in the Mid-South Tobacco Family sample

Payne

et al. 2007

Mol Psychiatry

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Previously, we reported a genome-wide scan for nicotine dependence (ND) in the African American (AA) sample of the Mid-South Tobacco Family (MSTF) cohort. In this study, we conducted a genome-wide scan in 629 individuals representing 200 nuclear families of European American (EA) origin of the MSTF cohort with the goals of identifying vulnerability loci for ND in the EAs and determining converging regions across the ethnic groups. We examined 385 autosomal microsatellite markers for ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerströ m test for ND (FTND). After performing linkage analyses using various methods implemented in the GENEHUNTER and SAGE programs, we found eight regions on chromosomes 2, 4, 9-12, 17 and 18 that met the criteria for suggestive linkage to at least one ND measure in the EA sample. Of these, the region on chromosome 4 at 43 cM showed suggestive linkage to indexed SQ, the HSI and the FTND, and the region on chromosome 9 at 24 cM showed suggestive linkage to the HSI and the FTND. To increase detection power, we analyzed a combined AA and EA sample using age, gender and ethnicity as covariates and found that the region on chromosome 12 near marker D12S372 showed significant linkage to SQ. Additionally, we found six regions on chromosomes 9-11, 13 and 18 that showed suggestive linkage to at least one ND measure in the combined sample. When we compared the linkage peaks detected for ND among the two samples and a combined sample, we found that four regions on chromosomes 9 (two regions), 11 and 18 overlapped. On the other hand, we identified five regions on chromosomes 2, 4, 10, 12 and 17 that showed linkage to ND only in the EA sample, and two regions on chromosomes 10 and 13 that showed linkage to ND only in the AA sample. For those linkages identified in only one sample, we found that the combined analysis of AA plus EA samples actually decreased the linkage signal. This indicates that some chromosomal regions may be more homogenous than others across the ethnic samples. All regions except for the one on chromosome 12 have been detected at nominally significant levels in other studies, providing independent replication of ND loci in different populations.

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Section: Discussionmentioning

confidence: 99%

Genome-wide linkage scan for nicotine dependence in European Americans and its converging results with African Americans in the Mid-South Tobacco Family sample

Payne

et al. 2007

Mol Psychiatry

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“…These studies do not provide any consistent evidence for the differential distribution of BDNF alleles among groups of patients with schizophrenia compared to controls. [77][78][79][80][81] However, these studies, in which the number of patients with schizophrenia ranged from 48 to 262, were somewhat underpowered to find a genetic association between the BDNF genotypes and schizophrenia, particularly as there exist numerous alleles of low frequency with this particular BDNF polymorphism.…”

Section: Evaluation Of the Evidence For Model 1fepiphenomenamentioning

confidence: 99%

Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia

et al. 2003

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Anatomical and molecular abnormalities of excitatory neurons in the dorsolateral prefrontal cortex (DLPFC) are found in schizophrenia. We hypothesized that brain-derived neurotrophic factor (BDNF), a protein capable of increasing pyramidal neuron spine density and augmenting synaptic efficacy of glutamate, may be abnormally expressed in the DLPFC of patients with schizophrenia. Using an RNase protection assay and Western blotting, we detected a significant reduction in BDNF mRNA (mean = 23%) and protein (mean = 40%) in the DLPFC of patients with schizophrenia compared to normal individuals. At the cellular level, BDNF mRNA was expressed at varying intensities in pyramidal neurons throughout layers II, III, V, and VI of DLPFC. In patients with schizophrenia; neuronal BDNF expression was decreased in layers III, V and VI. Our study demonstrates a reduction in BDNF production and availability in the DLPFC of schizophrenics, and suggests that intrinsic cortical neurons, afferent neurons, and target neurons may receive less trophic support in this disorder.

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“…4 This polymorphism has been tested for association with schizophrenia in five independent studies. [5][6][7][8][9] Three of these studies 6-8 used a case-control association strategy, one 9 used a family-based approach, while the other study used both the family and the casecontrol approach. 5 None of these data sets showed association between the BDNF dinucleotide repeat and schizophrenia.…”

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confidence: 99%

“…One of the previous studies was conducted in Japanese patients, 7 one in Roscommon County in Ireland, 5 one in 48 triads from Iowa, 9 and one in Spanish Caucasians. 8 The study by Krebs a w 2 = 6.48; 1 df; P = 0.010. b w 2 = 7.0; 1 df; P = 0.0081.…”

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confidence: 99%