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postgraduate thesis: Genetic and genomic mapping of common diseases

TitleGenetic and genomic mapping of common diseases
Authors
Advisors
Issue Date2012
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Guo, Y. [郭友玲]. (2012). Genetic and genomic mapping of common diseases. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5053386
Abstract Genome-wide mapping of susceptibility genes was conducted in two complex disorders of hypertension and epilepsy, allowing the dissection of the genetic architecture of these common diseases and related quantitative traits. The study performed comprehensive genetic analyses in a genome-wide scale, using different structure of data – sib-pairs and case-control samples. To identify genes influencing hypertension and blood pressure, a combined linkage and association study was conducted using over half a million SNPs genotyped in 328 siblings. Regions of significant linkage were identified for blood pressure traits on chromosomes 2q22.3 and 5p13.2, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P < 7  10-5) for hypertension. One candidate gene, PDC, was replicated in the family-based association tests. A two-stage genome-wide association study (GWAS) was performed in a total of 1,087 cases and 3,444 controls, to identify common susceptibility variants of epilepsy in Chinese. The combined analysis identified two association signals in CAMSAP1L1, rs2292096 [G] (P=1.0×10-8, OR =0.63) and rs6660197 [T] (P=9.9×10-7, OR=0.69), which are highly correlated, achieving genome-wide significance. One SNP (rs9390754, P = 1.7 × 10-5) in GRIK2 was refined as a previously-implicated association. In addition to SNPs, the assessment of CNVs in GWAS was performed, which could provide valuable clues to discover genes contributing to the heritability of epilepsy. A genome-wide scan for epilepsy through the use of DNA pooling also provides an alternative approach to reducing the substantial cost and thus increase efficiency in large-scale genetic association studies. The genome-wide mapping studies in families and unrelated individuals are complementary and together offer a comprehensive catalog of common variations and structural variants implicated for both quantitative and qualitative traits.
DegreeDoctor of Philosophy
SubjectHypertension - Genetic aspects.
Epilepsy - Genetic aspects.
Dept/ProgramPsychiatry
Persistent Identifierhttp://hdl.handle.net/10722/188267

 

DC FieldValueLanguage
dc.contributor.advisorCherny, SS-
dc.contributor.advisorSham, PC-
dc.contributor.authorGuo, Youling-
dc.contributor.author郭友玲-
dc.date.accessioned2013-08-27T08:02:58Z-
dc.date.available2013-08-27T08:02:58Z-
dc.date.issued2012-
dc.identifier.citationGuo, Y. [郭友玲]. (2012). Genetic and genomic mapping of common diseases. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5053386-
dc.identifier.urihttp://hdl.handle.net/10722/188267-
dc.description.abstract Genome-wide mapping of susceptibility genes was conducted in two complex disorders of hypertension and epilepsy, allowing the dissection of the genetic architecture of these common diseases and related quantitative traits. The study performed comprehensive genetic analyses in a genome-wide scale, using different structure of data – sib-pairs and case-control samples. To identify genes influencing hypertension and blood pressure, a combined linkage and association study was conducted using over half a million SNPs genotyped in 328 siblings. Regions of significant linkage were identified for blood pressure traits on chromosomes 2q22.3 and 5p13.2, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P < 7  10-5) for hypertension. One candidate gene, PDC, was replicated in the family-based association tests. A two-stage genome-wide association study (GWAS) was performed in a total of 1,087 cases and 3,444 controls, to identify common susceptibility variants of epilepsy in Chinese. The combined analysis identified two association signals in CAMSAP1L1, rs2292096 [G] (P=1.0×10-8, OR =0.63) and rs6660197 [T] (P=9.9×10-7, OR=0.69), which are highly correlated, achieving genome-wide significance. One SNP (rs9390754, P = 1.7 × 10-5) in GRIK2 was refined as a previously-implicated association. In addition to SNPs, the assessment of CNVs in GWAS was performed, which could provide valuable clues to discover genes contributing to the heritability of epilepsy. A genome-wide scan for epilepsy through the use of DNA pooling also provides an alternative approach to reducing the substantial cost and thus increase efficiency in large-scale genetic association studies. The genome-wide mapping studies in families and unrelated individuals are complementary and together offer a comprehensive catalog of common variations and structural variants implicated for both quantitative and qualitative traits.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B50533861-
dc.subject.lcshHypertension - Genetic aspects.-
dc.subject.lcshEpilepsy - Genetic aspects.-
dc.titleGenetic and genomic mapping of common diseases-
dc.typePG_Thesis-
dc.identifier.hkulb5053386-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplinePsychiatry-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5053386-
dc.date.hkucongregation2013-

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