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Torben A Kruse

Publications and source records attributed to Torben A Kruse.

29 records · Page 2Linked to original sources
PubMed2004

Apolipoprotein E genotype frequency patterns in aged Danes as revealed by logistic regression models.

Although the ApoE gene has been intensively studied in aging research, most of the studies conducted so far have been based on the traditional case-control design with subjects consisting of young controls and long-lived cases. The genotype frequency pattern in and between the two age-groups has been rarely investigated due to limitations in either research design or data analytical method. In this study, we genotyped 748 individuals (including both twin pairs and unrelated individuals) aged from 73 to 95 with aim at examining the genotype frequency trajectory of ApoE gene at high ages. Binomial and multinomial logistic regression models have been applied to model the gene frequency as a function of age and to investigate the modes of gene function (dominant, recessive, additive). The generalized estimation equations (GEEs) are introduced to account for the intra-pair genotype correlation in the twin pairs included in the data. Both the observed and the fitted frequencies show a constantly declining pattern of ApoE epsilon4 allele as age advances indicating a significant and steadily deleterious effect of the dominant allele that increases the hazard of death at high ages.

Aged↗
PubMed2003

Analysis of transmission of novel polymorphisms in the somatostatin receptor 5 (SSTR5) gene in patients with autism.

Infantile autism is a pervasive developmental disorder with a strong genetic component. The mode of inheritance appears to be complex and no specific susceptibility genes have yet been identified. Chromosome 16p13.3 may contain a susceptibility gene based on findings from genome scans and reports of chromosome abnormalities in individuals with autism. The somatostatin receptor 5 (SSTR5) gene is located on chromosome 16p13.3 and is thus a positional candidate gene for autism. SSTR5 may also be a functional candidate gene for autism because somatostatin inhibits growth hormone secretion, and increased growth hormone response has been reported in some individuals with autism. Moreover, the somatostatinergic system interacts with the dopaminergic system, which has been hypothesized to be involved in the etiology of autism; in particular, somatostatin secretion is regulated by dopamine, and the dopamine D2 receptor and the SSTR5 receptor interact to form a receptor complex with enhanced functional activity. In the present study, we tested whether the alleles of twelve new single nucleotide polymorphisms (SNPs) in the SSTR5 gene were preferentially transmitted, using the transmission disequilibrium test (TDT) in a sample of 79 trios with autism (18 from Denmark and 61 from France). Furthermore, we combined four missense SNPs into haplotypes and searched for preferential transmission using the program TRANSMIT. No significant preferential transmission of the alleles and haplotypes of the twelve SNPs was found. Our results do not suggest the SSTR5 gene as a susceptibility gene for autism.

Autistic Disorder↗
PubMed2003

Genome wide scan using homozygosity mapping and linkage analyses of a single pedigree with affective disorder suggests oligogenic inheritance.

The present study reports results from a genome scan on a family with bipolar affective disorder in which the parents are first cousins and four of the offsprings and one grandchild have affective disorder. The study searched for risk loci for affective disorder by searching for homozygous segments or more complex inherited loci using parametric and non-parametric multipoint linkage analysis. In addition dominant, multipoint, affecteds-only linkage analyses were performed as a supplement to previous analyses. On chromosomes 2q31.3, 10, 12q24, and 21q22.3 evidence for a risk locus was obtained by parametric and/or non-parametric linkage analyses and by haplotype sharing. As other studies have found significant or suggestive linkage to bipolar disorder in these chromosome regions this suggests that an oligogenic mode of inheritance is possible in this family involving at least some of the loci. Finally, the work discusses whether homozygosity mapping using parametric and non-parametric linkage analyses may be of value for complex diseases including rare subphenotypes of such disorders.

Bipolar Disorder↗
PubMed2003

Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder.

Genome scans of bipolar disorder (BPD) have not produced consistent evidence for linkage. The rank-based genome scan meta-analysis (GSMA) method was applied to 18 BPD genome scan data sets in an effort to identify regions with significant support for linkage in the combined data. The two primary analyses considered available linkage data for "very narrow" (i.e., BP-I and schizoaffective disorder-BP) and "narrow" (i.e., adding BP-II disorder) disease models, with the ranks weighted for sample size. A "broad" model (i.e., adding recurrent major depression) and unweighted analyses were also performed. No region achieved genomewide statistical significance by several simulation-based criteria. The most significant P values (<.01) were observed on chromosomes 9p22.3-21.1 (very narrow), 10q11.21-22.1 (very narrow), and 14q24.1-32.12 (narrow). Nominally significant P values were observed in adjacent bins on chromosomes 9p and 18p-q, across all three disease models on chromosomes 14q and 18p-q, and across two models on chromosome 8q. Relatively few BPD pedigrees have been studied under narrow disease models relative to the schizophrenia GSMA data set, which produced more significant results. There was no overlap of the highest-ranked regions for the two disorders. The present results for the very narrow model are promising but suggest that more and larger data sets are needed. Alternatively, linkage might be detected in certain populations or subsets of pedigrees. The narrow and broad data sets had considerable power, according to simulation studies, but did not produce more highly significant evidence for linkage. We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region.

Bipolar Disorder↗
PubMed2002

Investigation of two variants in the DOPA decarboxylase gene in patients with autism.

Though genetic risk factors are important for the development of autism, no specific risk alleles have yet been identified. DOPA decarboxylase (DDC) is involved in both the catecholaminergic and serotonergic pathways and may be considered a functional candidate gene for autism. The present study is the first to test if two new variants of possible functional significance in the DDC gene increase the susceptibility to autism. A total of 90 parent-offspring trios recruited in Denmark and France were investigated using the transmission disequilibrium test (TDT). We found no evidence of linkage disequilibrium between autism and either of the two polymorphisms. Nor did we find linkage disequilibrium between autism and haplotypes of the two variants using a multiallelic TDT. These findings suggest that the DDC gene is unlikely to play a major role in the development of autism in our data set.

Adolescent↗
PubMed2002

Search for a shared segment on chromosome 10q26 in patients with bipolar affective disorder or schizophrenia from the Faroe Islands.

Previous linkage studies have suggested a new locus for bipolar affective disorder and possibly also for schizophrenia on chromosome 10q26. We searched for allelic association and chromosome segment and haplotype sharing on chromosome 10q26 among distantly related patients with bipolar affective disorder or schizophrenia and controls from the relatively isolated population of the Faroe Islands by investigating 22 microsatellite markers from a 35 cM region. We used a combined approach with both assumption free tests and tests based on genealogical relationships. The 6.5 cM region between D10S1230 and D10S2322, which has been implied in previous linkage analyses, received some support. A search for segment sharing yielded empirical P-values around 0.02 among patients with bipolar affective disorder and around 0.03 for patients with schizophrenia. For both disorders combined allelic association yielded empirical P-values around 0.003 at marker D10S1723. A haplotype data mining approach supported haplotype sharing in this region. In another, more distal, 11.5 cM region between markers D10S214 and D10S505, which has received support in previous linkage studies, increased haplotype sharing in patients with bipolar affective disorder was supported by Fisher's exact test, tests based on genealogy and by haplotype data mining. Our findings yield some support for a risk gene for bipolar affective disorder and possibly also for schizophrenia.

Alleles↗
PubMed2002

[Pycnodysostosis--common ancestor of some Danish patients. Examination and diagnosis based on molecular genetics].

Eight patients with pycnodysostosis from six Danish families were examined for mutations in the cathepsin K gene. Three different mutations are the cause of pycnodysostosis in the six families--five of whom come from Ringkøbing County and one from Vejle County. One mutation has a high frequency in the families from Ringkoebing County. The five families are related through a common ancestor, who introduced the mutation around the year 1100. The disease is described with respect to aetiology, symptoms, prognosis, diagnosis, and symptomatic treatment. Research in pycnodysostosis may bring important knowledge to the understanding of related diseases, such as osteoporosis.

Cathepsins↗
PubMed2002

Linkage disequilibrium and demographic history of the isolated population of the Faroe Islands.

The isolated population of the Faroe Islands has a history of recent expansion after being limited to a small size for centuries. Such an isolated population may be ideal for linkage disequilibrium mapping of disease genes if linkage disequilibrium (LD) extends over large regions. Analyses of 18 markers on 12q24.3, spanning a region of 4.3 Mb (16 cM), revealed extensive LD in the Faroese population. Maximum LD was found between marker pairs separated by more than 3.8 Mb. The same region had a maximum LD of only 1.2 and 1.4 Mb respectively in two outbred Danish and British populations analysed here for comparison. The analyses of gene diversity excess at 15 unlinked microsatellite markers did not reveal any sign of a severe bottleneck to have occurred within approximately 1200 years' history of the Faroese population. The extensive LD in this population may, therefore, have arisen primarily by random genetic drift. The implications for future gene mapping studies are discussed.

Atlantic Islands↗