No evidence for linkage of chromosome 22 markers to schizophrenia in Southern African Bantu-speaking families

Riley, Brien P.; Mogudi-Carter, M.; Jenkins, Trefor; Williamson, Robert

doi:10.1002/(sici)1096-8628(19961122)67:6<515::aid-ajmg2>3.0.co;2-g

Cited by 26 publications

(13 citation statements)

References 28 publications

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“…1 The COMT gene is located on chromosome 22q11, a region that showed positive results in some linkage studies [2][3][4] but was negative in others. [5][6][7][8] The region is also associated with the velocardiofacial syndrome (VCFS), 9 a genetic disorder characterized by cleft palate, heart defects and characteristic facial appearance. Studies have shown that patients with VCFS are at increased risk for schizophrenia.…”

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Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families

et al. 2004

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The enzyme catechol-o-methyltransferase (COMT) transfers a methyl group from adenosylmethionine to catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. In this article, we reported our study of association of COMT with schizophrenia in Irish families with a high density of schizophrenia. Three single nucleotide polymorphisms (SNPs) were genotyped for the 274 such families and within-family transmission disequilibrium tests were performed. SNP rs4680, which is the functional Val/Met polymorphism, showed modest association with the disease by the TRANSMIT, FBAT and PDT programs, while the other two SNPs were negative. These SNPs showed lower level of LDs with each other in the Irish subjects than in Ashkenazi Jews. Haplotype analysis indicated that a haplotype, haplotype A-G-A for SNPs rs737865-rs4680-rs165599, was preferentially transmitted to the affected subjects. This was different from the reported G-G-G haplotype found in Ashkenazi Jews, but both haplotypes shared the Val allele. We concluded that COMT gene is associated with schizophrenia and carries a small but significant risk to the susceptibility in the Irish subjects. Molecular Psychiatry (2004) 9, 962-967.

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Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families

et al. 2004

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“…Subsequent replication attempts showed weak evidence for linkage 23,24 or linkage disequilibrium, 25,26 although some studies failed to show evidence for linkage. [27][28][29] . We analyzed eight markers spanning 47 cM in this chromosomal region and found a maximum heterogeneity lod score of 0.89 with marker D22S427 (dominant affecteds only model, diagnostic model 1) ( Table 1).…”

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Linkage analysis of putative schizophrenia gene candidate regions on chromosomes 3p, 5q, 6p, 8p, 20p and 22q in a population-based sampled Finnish family set

et al. 1998

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During the past decade numerous studies have been published describing chromosomal regions potentially linked with schizophrenia. Unfortunately, none of these studies has been able to conclusively identify any specific gene that predisposes to schizophrenia. Typically evidence for linkage is seen on large chromosomal regions, as expected, containing tens or even hundreds of genes. Furthermore, attempts to replicate the findings have rarely been successful leaving a confusion about the existence of predisposing genes for schizophrenia in a particular region of the genome. We have carried out linkage analysis in a set of 62 pedigrees rising from a genetically isolated population of Finland with markers on six chromosomal regions earlier suggested to harbor predisposing genes for schizophrenia, namely 3p, 1 5q, 2,3 6p, 4 8p, 1 20p, 5 and 22q. 6,7 We were not able to find significant evidence for linkage on any of these chromosomal regions. However, some support for linkage was found on all studied chromosomal regions, except 3p.We identified all Finnish patients with schizophrenia born between 1940 and 1969 (n = 29 124). 8 Patients who had received disability pension or free medication because of schizophrenia were identified from two registers of the Social Insurance Institution, and patients who had been hospitalized for schizophrenia were identified from the National Hospital Discharge Register. All three registers were computerized in 1968; ICD-8 diagnostic criteria and codes were used before 1987, since when psychiatric diagnoses have been coded according to ICD-9 applying DSM-III-R diagnostic criteria. We accepted all probands with a 295 diagnosis according to the ICD-8 and ICD-9 numbering scheme; this includes patients with schizophrenia, schizophreniform disorder, and schizoaffective disorder. Parents and siblings were identified from the National Population Register, and information on these relatives was linked to the health care registers to obtain data on their hospital treatments, pensions, and free medications.From these pedigrees, families with at least three affected family members were identified (n = 312), and those with at least one unaffected and three affected children were asked to participate in the study. If both parents were affected, the family was excluded. Diagnoses were confirmed as described in methods. Some families refused to participate and some were excluded because of uncertain diagnoses, and finally 62 families were used for molecular genetic studies out of 102 families who were asked to participate. Three different diagnostic classes were constructed as follows: class 1 contained 137 cases of DSM-IV schizophrenia, class 2 added 23 cases with schizoaffective disorder, and class 3 another 29 individuals with schizophrenia spectrum conditions (schizophreniform disorder, schizotypal personality disorder, schizoid personality disorder, delusional disorder, brief psychotic disorder, and psychotic disorder NOS). Patients with bipolar disorder or major depressive disorder were classifie...

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“…Riley and collaborators were the first to investigate schizophrenia in a South African population and published a series of manuscripts on linkage analyses in a cohort of Bantu-speaking black South Africans. [17][18][19][20][21][22] Areas of implied linkage to schizophrenia identified by these studies are displayed in Table II and include genomic regions surrounding the coding regions for subunits of N-methyl-D-aspartate (NMDA) receptors 19 and the alpha7 acetylcholine receptor gene (CHRNA7). 22 NMDA receptors form part of the glutamate system, which is believed to be of relevance as NMDA antagonists (i.e.…”

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confidence: 99%

“…358 mentioned earlier, found no evidence for 22q linkage. 18 These data indicate that genetic, as well as cultural, differences exist between the black African Xhosa schizophrenia patients and those of Caucasian ethnicity. Therefore, results obtained from one population cannot necessarily be extrapolated to another.…”

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Psychiatric genetics in South Africa: cutting a rough diamond

Wright¹,

Niehaus²,

Koen³

et al. 2011

Afr. J. Psych

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Psychiatric disorders place a considerable healthcare burden on South African society. Incorporating genetic technologies into future treatment plans offers a potential mechanism to reduce this burden. This review focuses on psychiatric genetic research that has been performed in South African populations with regards to obsessive-compulsive disorder, schizophrenia and bipolar disorder. Preliminary findings from these studies suggest that data obtained in developed countries cannot necessarily be extrapolated to South African population groups. Psychiatric genetic studies in South Africa seem to involve relatively low-cost methodologies and only a limited number of large national collaborative studies. Future research in South Africa should therefore aim to incorporate highthroughput technologies into large scale psychiatric studies through the development of collaborations. On a global level, the vast majority of psychiatric genetic studies have been performed in non-African populations. South Africa, as the leading contributor to scientific research in Africa, may provide a foundation for addressing this disparity and strengthening psychiatric genetic research on the continent. Although the elucidation of the genetic architecture of psychiatric disorders has proved challenging, examining the unique genetic profiles found in South African populations could provide valuable insight into the genetics of psychiatric disorders. 356 pharmacogenetic studies). The Afrikaners are an example of a homogenous population as they arose from a small founder population of 1000-2000 Dutch immigrants that arrived in South Africa in the 17th century. 6,7 The ancient southern African Khoisan population possesses the highest level of genetic diversity reported to date, while the Mixed Ancestry population shows the greatest global admixture of any of the world's populations analysed thus far. 8 Additionally, the Nguni-speaking Xhosa population shows a significant genetic contribution from the Khoisan in their genomes, reflecting admixture between these ancient individuals and ancestral Bantu populations; artefacts of this exchange are also linguistically evident through the click consonants present in the isiXhosa language. 8,9 The prevalence of psychiatric disorders in the different ethnic groups of South Africa is not known, although evidence from the South African Stress and Health Study 10 suggests very little difference from non-African populations. However, alarmingly, it appears that the majority of individuals suffering from psychiatric disorders in South Africa do not receive treatment. 11 Revised burden of disease estimates place neuropsychiatric disorders as the third highest cause of disability-adjusted life years in the country, mainly due to the extended morbidity of such conditions. 12 Unipolar depression, alcohol use, bipolar affective disorder, schizophrenia, drug use, obsessive-compulsive disorder (OCD) and panic disorder are neuropsychiatric disorders that fall into the top 20 causes of years lived with ...

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No evidence for linkage of chromosome 22 markers to schizophrenia in Southern African Bantu-speaking families

Cited by 26 publications

References 28 publications

Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families

Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families

Linkage analysis of putative schizophrenia gene candidate regions on chromosomes 3p, 5q, 6p, 8p, 20p and 22q in a population-based sampled Finnish family set

Psychiatric genetics in South Africa: cutting a rough diamond

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