Genetic studies of stroke in Northern Sweden
Stroke is a common disorder of later life with a complex etiology, including both environmental and genetic risk factors. The inherited predisposition is challenging to study due to the complexity of the stroke phenotype. Genetic studies in an isolated population have successfully identified a posit...
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Medicinsk biovetenskap
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ftumeauniv:oai:DiVA.org:umu-887 2023-10-09T21:54:30+02:00 Genetic studies of stroke in Northern Sweden Nilsson Ardnor, Sofie 2006 application/pdf http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-887 eng eng Medicinsk biovetenskap Umeå : Medicinsk biovetenskap Umeå University medical dissertations, 0346-6612 1060 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-887 urn:isbn:91-7264-191-6 info:eu-repo/semantics/openAccess stroke linkage genome wide scan susceptibility loci association candidade gene PDE4D PIK3R1 extended pedigree Medical Genetics Medicinsk genetik Doctoral thesis, comprehensive summary info:eu-repo/semantics/doctoralThesis text 2006 ftumeauniv 2023-09-22T13:48:00Z Stroke is a common disorder of later life with a complex etiology, including both environmental and genetic risk factors. The inherited predisposition is challenging to study due to the complexity of the stroke phenotype. Genetic studies in an isolated population have successfully identified a positional candidate gene for stroke, phosphodiesterase 4D (PDE4D). The aim of this thesis was to identify stroke susceptibility loci and positional candidate genes, taking advantage of low genetic variation in the northern Sweden population. All stroke cases were identified in a population-based stroke registry at the northern Sweden MONICA Centre. 56 families containing multiple cases of stroke and a follow up set of an additional 53 families were used for linkage studies. For association studies, 275 cases of first ever stroke together with 550 matched community controls were included. In paper I, we used a candidate region approach to investigate the PDE4D region on chromosome 5q. Linkage was obtained with a maximum allele-sharing LOD score of 2.06; P = 0.001. However, no significant association of ischemic stroke to the previously defined at-risk allele in PDE4D was observed. We next performed a genome wide linkage scan to explore new susceptibility loci for common forms of stroke (paper II). Non-parametric multipoint linkage analysis yielded allele-sharing LOD scores > 1.2 at nine locations; 1p34, 5q13, 7q35, 9q22, 9q34, 13q32, 14q32, 18p11, 20q13. The highest allele-sharing LOD score was obtained on chromosome 18p (LOD = 2.14). Fine mapping resulted in increased allele-sharing LOD scores for chromosome 5q13 and 9q22. In the follow up analysis of the nine regions, including all 109 families, the highest allele-sharing LOD scores were obtained on chromosomes 5q, 13q and 18p although none reached the initial genome wide values. In paper III, we focused on the chromosome 5q region, and further mapping and haplotype analysis in the families was performed. A common 1 cM haplotype was found to be shared among affected ... Doctoral or Postdoctoral Thesis Northern Sweden Umeå University: Publications (DiVA) |
institution |
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Umeå University: Publications (DiVA) |
op_collection_id |
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language |
English |
topic |
stroke linkage genome wide scan susceptibility loci association candidade gene PDE4D PIK3R1 extended pedigree Medical Genetics Medicinsk genetik |
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stroke linkage genome wide scan susceptibility loci association candidade gene PDE4D PIK3R1 extended pedigree Medical Genetics Medicinsk genetik Nilsson Ardnor, Sofie Genetic studies of stroke in Northern Sweden |
topic_facet |
stroke linkage genome wide scan susceptibility loci association candidade gene PDE4D PIK3R1 extended pedigree Medical Genetics Medicinsk genetik |
description |
Stroke is a common disorder of later life with a complex etiology, including both environmental and genetic risk factors. The inherited predisposition is challenging to study due to the complexity of the stroke phenotype. Genetic studies in an isolated population have successfully identified a positional candidate gene for stroke, phosphodiesterase 4D (PDE4D). The aim of this thesis was to identify stroke susceptibility loci and positional candidate genes, taking advantage of low genetic variation in the northern Sweden population. All stroke cases were identified in a population-based stroke registry at the northern Sweden MONICA Centre. 56 families containing multiple cases of stroke and a follow up set of an additional 53 families were used for linkage studies. For association studies, 275 cases of first ever stroke together with 550 matched community controls were included. In paper I, we used a candidate region approach to investigate the PDE4D region on chromosome 5q. Linkage was obtained with a maximum allele-sharing LOD score of 2.06; P = 0.001. However, no significant association of ischemic stroke to the previously defined at-risk allele in PDE4D was observed. We next performed a genome wide linkage scan to explore new susceptibility loci for common forms of stroke (paper II). Non-parametric multipoint linkage analysis yielded allele-sharing LOD scores > 1.2 at nine locations; 1p34, 5q13, 7q35, 9q22, 9q34, 13q32, 14q32, 18p11, 20q13. The highest allele-sharing LOD score was obtained on chromosome 18p (LOD = 2.14). Fine mapping resulted in increased allele-sharing LOD scores for chromosome 5q13 and 9q22. In the follow up analysis of the nine regions, including all 109 families, the highest allele-sharing LOD scores were obtained on chromosomes 5q, 13q and 18p although none reached the initial genome wide values. In paper III, we focused on the chromosome 5q region, and further mapping and haplotype analysis in the families was performed. A common 1 cM haplotype was found to be shared among affected ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Nilsson Ardnor, Sofie |
author_facet |
Nilsson Ardnor, Sofie |
author_sort |
Nilsson Ardnor, Sofie |
title |
Genetic studies of stroke in Northern Sweden |
title_short |
Genetic studies of stroke in Northern Sweden |
title_full |
Genetic studies of stroke in Northern Sweden |
title_fullStr |
Genetic studies of stroke in Northern Sweden |
title_full_unstemmed |
Genetic studies of stroke in Northern Sweden |
title_sort |
genetic studies of stroke in northern sweden |
publisher |
Medicinsk biovetenskap |
publishDate |
2006 |
url |
http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-887 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
Umeå University medical dissertations, 0346-6612 1060 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-887 urn:isbn:91-7264-191-6 |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1779318086576373760 |