請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57286
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳為堅(Wei J. Chen) | |
dc.contributor.author | Yu-Hsuan Shih | en |
dc.contributor.author | 施又瑄 | zh_TW |
dc.date.accessioned | 2021-06-16T06:40:23Z | - |
dc.date.available | 2019-10-20 | |
dc.date.copyright | 2014-10-20 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-07-29 | |
dc.identifier.citation | Ancin, I., Santos, J.L., Teijeira, C., Sanchez-Morla, E.M., Bescos, M.J., Argudo, I., Torrijos, S., Vazquez-Alvarez, B., De La Vega, I., Lopez-Ibor, J.J., Barabash, A., Cabranes-Diaz, J.A., 2010. Sustained attention as a potential endophenotype for bipolar disorder. Acta Psychiatrica Scandinavica 122(3), 235-245.
Beck, L.H., Bransome, E.D., Jr., Mirsky, A.F., Rosvold, H.E., Sarason, I., 1956. A continuous performance test of brain damage. Journal of Consulting and Cilnical Psychology 20(5), 343-350. Benyamin, B., Wilson, V., Whalley, L.J., Visscher, P.M., Deary, I.J., 2005. Large, consistent estimates of the heritability of cognitive ability in two entire populations of 11-year-old twins from Scottish mental surveys of 1932 and 1947. Behavior Genetics 35(5), 525-534. Bilder, R.M., Howe, A., Novak, N., Sabb, F.W., Parker, D.S., 2011. The genetics of cognitive impairment in schizophrenia: a phenomic perspective. Trends in Cognitive Sciences 15(9), 428-435. Bray, N.J., Owen, M.J., 2001. Searching for schizophrenia genes. Trends in Molecular Medicine 7(4), 169-174. Cardno, A.G., Gottesman, II, 2000. Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. American Journal of Medical Genetics 97(1), 12-17. Chen, W.J., Chang, C.H., Liu, S.K., Hwang, T.J., Hwu, H.G., 2004. Sustained attention deficits in nonpsychotic relatives of schizophrenic patients: a recurrence risk ratio analysis. Biological Psychiatry 55(10), 995-1000. Chen, W.J., Hsiao, C.K., Hsiao, L.L., Hwu, H.G., 1998. Performance of the Continuous Performance Test among community samples. Schizophrenia Bulletin 24(1), 163-174. Chiang, H.L., Gau, S.S., 2014. Impact of executive functions on school and peer functions in youths with ADHD. Research in Developmental Disabilities 35(5), 963-972. Chien, I.C., Chou, Y.J., Lin, C.H., Bih, S.H., Chou, P., Chang, H.J., 2004. Prevalence and incidence of schizophrenia among national health insurance enrollees in Taiwan, 1996-2001. Psychiatry and Clinical Neurosciences 58(6), 611-618. Fanous, A.H., Kendler, K.S., 2005. Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: searching for a framework. Molecular Psychiatry 10(1), 6-13. Fanous, A.H., Zhou, B., Aggen, S.H., Bergen, S.E., Amdur, R.L., Duan, J., Sanders, A.R., Shi, J., Mowry, B.J., Olincy, A., Amin, F., Cloninger, C.R., Silverman, J.M., Buccola, N.G., Byerley, W.F., Black, D.W., Freedman, R., Dudbridge, F., Holmans, P.A., Ripke, S., Gejman, P.V., Kendler, K.S., Levinson, D.F., 2012. Genome-wide association study of clinical dimensions of schizophrenia: polygenic effect on disorganized symptoms. American Journal of Psychiatry 169(12), 1309-1317. Gejman, P.V., Sanders, A.R., Kendler, K.S., 2011. Genetics of schizophrenia: new findings and challenges. Annual Review of Genomics and Human Genetics 12, 121-144. Goldberg, T.E., Weinberger, D.R., Berman, K.F., Pliskin, N.H., Podd, M.H., 1987. Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test. Archives of General Psychiatry 44(11), 1008-1014. Gottesman, II, Gould, T.D., 2003. The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160(4), 636-645. Greenwood, T.A., Braff, D.L., Light, G.A., Cadenhead, K.S., Calkins, M.E., Dobie, D.J., Freedman, R., Green, M.F., Gur, R.E., Gur, R.C., Mintz, J., Nuechterlein, K.H., Olincy, A., Radant, A.D., Seidman, L.J., Siever, L.J., Silverman, J.M., Stone, W.S., Swerdlow, N.R., Tsuang, D.W., Tsuang, M.T., Turetsky, B.I., Schork, N.J., 2007. Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Archives of General Psychiatry 64(11), 1242-1250. Howie, B., Fuchsberger, C., Stephens, M., Marchini, J., Abecasis, G.R., 2012. Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nature Genetics 44(8), 955-959. Hwu, H.-G., Faraone, S.V., Liu, C.-M., Chen, W.J., Liu, S.-K., Shieh, M.-H., Hwang, T.-J., Tsuang, M.-M., OuYang, W.-C., Chen, C.-Y., Chen, C.-C., Lin, J.-J., Chou, F.H.-C., Chueh, C.-M., Liu, W.-M., Hall, M.-H., Tsuang, M.T., 2005. Taiwan schizophrenia linkage study: The field study. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 134B(1), 30-36. Jun, G., Moncaster, J.A., Koutras, C., Seshadri, S., Buros, J., McKee, A.C., Levesque, G., Wolf, P.A., St George-Hyslop, P., Goldstein, L.E., Farrer, L.A., 2012. delta-Catenin is genetically and biologically associated with cortical cataract and future Alzheimer-related structural and functional brain changes. PLoS One 7(9), e43728. Kim, J.M., Lee, K.H., Jeon, Y.J., Oh, J.H., Jeong, S.Y., Song, I.S., Kim, J.M., Lee, D.S., Kim, N.S., 2006. Identification of genes related to Parkinson's disease using expressed sequence tags. DNA Research 13(6), 275-286. Li, Y., Willer, C., Sanna, S., Abecasis, G., 2009. Genotype Imputation. Annual Review of Genomics and Human Genetics 10(1), 387-406. Li, Y., Willer, C.J., Ding, J., Scheet, P., Abecasis, G.R., 2010. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genetic Epidemiology 34(8), 816-834. Lien, Y.J., Hsiao, P.C., Liu, C.M., Faraone, S.V., Tsuang, M.T., Hwu, H.G., Chen, W.J., 2011. A genome-wide linkage scan for distinct subsets of schizophrenia characterized by age at onset and neurocognitive deficits. PLoS One 6(8), e24103. Lin, C.C., Chen, W.J., Yang, H.J., Hsiao, C.K., Tien, A.Y., 2000. Performance on the Wisconsin Card Sorting Test among adolescents in Taiwan: norms, factorial structure, and relation to schizotypy. Journal of Clinical and Experimental Neuropsychology 22(1), 69-79. Lin, S.H., Liu, C.M., Hwang, T.J., Hsieh, M.H., Hsiao, P.C., Faraone, S.V., Tsuang, M.T., Hwu, H.G., Chen, W.J., 2012. Performance on the Wisconsin Card Sorting Test in Families of Schizophrenia Patients With Different Familial Loadings. Schizophrenia Bulletin 39(3), 537-546. Medina, M., Marinescu, R.C., Overhauser, J., Kosik, K.S., 2000. Hemizygosity of delta-catenin (CTNND2) is associated with severe mental retardation in cri-du-chat syndrome. Genomics 63(2), 157-164. Nurnberger, J.I., Jr., Blehar, M.C., Kaufmann, C.A., York-Cooler, C., Simpson, S.G., Harkavy-Friedman, J., Severe, J.B., Malaspina, D., Reich, T., 1994. Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. Archives of General Psychiatry 51(11), 849-859; discussion 863-844. Picchioni, M.M., Murray, R.M., 2007. Schizophrenia. British Medical Journal 335(7610), 91-95. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., de Bakker, P.I., Daly, M.J., Sham, P.C., 2007. PLINK: a tool set for whole-genome association and population-based linkage analyses. The American Journal of Human Genetics 81(3), 559-575. Purcell, S.M., Wray, N.R., Stone, J.L., Visscher, P.M., O'Donovan, M.C., Sullivan, P.F., Sklar, P., 2009. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460(7256), 748-752. R. K. Heaton, G.J.C., J. L. Talley, G. G. Kay, and G. Curtiss., 1993. Wisconsin Card Sorting Test Manual: Revised and expanded. Psychological Assessment Resources Inc, Odessa, FL, . Robinson, A.L., Heaton, R.K., Lehman, R.A., Stilson, D.W., 1980. The utility of the Wisconsin Card Sorting Test in detecting and localizing frontal lobe lesions. Journal of Consulting and Clinical Psychology 48(5), 605-614. Schreiber, J.E., Possin, K.L., Girard, J.M., Rey-Casserly, C., 2014. Executive function in children with attention deficit/hyperactivity disorder: the NIH EXAMINER battery. Journal of the International Neuropsychological Society 20(1), 41-51. Sullivan, P.F., Kendler, K.S., Neale, M.C., 2003. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Archives of General Psychiatry 60(12), 1187-1192. van Os, J., Kapur, S., 2009. Schizophrenia. Lancet 374(9690), 635-645. Vaughn, A.J., Epstein, J.N., Rausch, J., Altaye, M., Langberg, J., Newcorn, J.H., Hinshaw, S.P., Hechtman, L., Arnold, L.E., Swanson, J.M., Wigal, T., 2011. Relation between outcomes on a continuous performance test and ADHD symptoms over time. Journal of Abnormal Child Psychology 39(6), 853-864. Vrijenhoek, T., Buizer-Voskamp, J.E., van der Stelt, I., Strengman, E., Sabatti, C., Geurts van Kessel, A., Brunner, H.G., Ophoff, R.A., Veltman, J.A., 2008. Recurrent CNVs disrupt three candidate genes in schizophrenia patients. The American Journal of Human Genetics 83(4), 504-510. Wang, K.S., Liu, X.F., Aragam, N., 2010. A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. Schizophr Research 124(1-3), 192-199. Wolf, L.E., Cornblatt, B.A., Roberts, S.A., Shapiro, B.M., Erlenmeyer-Kimling, L., 2002. Wisconsin Card Sorting deficits in the offspring of schizophrenics in the New York High-Risk Project. Schizophr Research 57(2-3), 173. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57286 | - |
dc.description.abstract | 思覺失調症在基因型及臨床表徵都具有很高的異質性,其中神經認知功能受損在病人中具有高遺傳度。因此,利用神經認知功能指標做為內表型,將可以找到與神經認知功能顯著相關之單核苷酸多型性 (single-nucleotide polymorphisms, SNPs),並發現潛在之多基因影響。本研究為全基因組關聯的單純病例研究,期望納入神經認知功能缺損做為量性變項 (Quantitative trait),可找到與思覺失調症及神經認知功能相關之修飾基因 (Modifier gene),此外,我們也利用多基因分數分析,探討神經認知功能缺損在思覺失調症的病人是否受到多基因的影響。本研究共納入165位有思覺失調症的病人,每位病人都會有642,832個SNPs資料以及14個來自於連續操作測驗 (Continuous Performance Test, CPT) 及威斯康辛卡分類測驗 (Wisconsin Card Sorting Test, WCST) 的神經認知功能指標。在經過質量管控 (Quality control) 後,共有564,110個SNPs資料留下做後續分析。首先,我們使用主成分分析,將14個指標化簡成2個分別解釋總變異36.11%及18.30%的主成分,並探討其與SNPs之相關,但由於樣本數的限制並未偵測到任何全基因組相關。此外,為了進行多基因分數分析,我們利用MaCH及MiniMac軟體進行缺失基因資料的填補,並將可能具有高度連鎖不平衡之SNPs去除,因此共240,579個被納入進行多基因分析。接著,利用隨機抽樣將165位個案分成探索組 (n=83) 與驗證組 (n=82),我們發現由25個SNPs所得到的多基因分數,可成功預測病人在注意力的表現。此外,由219個SNPs所計算的多基因分數,可有效預測病人在執行能力的表現。由此可證明,思覺失調症病人在神經認知功能的表現,可能不是由於單一基因所造成之影響,而是受到多基因共同影響所致。 | zh_TW |
dc.description.abstract | Schizophrenia is considered to be genetically and phenotypically heterogeneous. The high heritability of neurocognitive impairments found in patients with schizophrenia suggests that these impairments may serve as an endophenotype resulting from a set of underlying genes in a mode of polygenic effects. In this study, a total of 165 schizophrenia patients were selected and these subjects were subjected to genotyping for 642,832 single nucleotide polymorphisms (SNPs). After quality control, 564,110 SNPs were left. We then performed principal component analysis (PCA) on 14 indices of the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST). Two orthogonal principal components (PC1 and PC2) identified with PCA explained 36.11% and 18.30% of the total variance, respectively. Then the two PCs were investigated for association with SNPs. Because of small sample size in this study, however, we were unable to detect SNPs associated with neurocognitive performance in schizophrenia with genome-wide significance. For exploring the polygenic effect, polygenic score analysis was conducted on 240,579 LD-based pruning SNPs (r2 > 0.5), which were imputed using MaCH and MiniMac. The sample was first randomly divided into a learning set (n = 83) and a test set (n = 82). Then the effect size (β) for the results of association test in the learning set was used to develop a linear model to generate scores in the test set. The sustained attention demonstrated a significant association (p = 0.03) with the PC1 polygenic score at a threshold of p = 0.0001 (25 markers), For the executive function, when polygenic scores in the test set was calculated based on the results of the best 0.1% of SNPs (219 markers) in the association study of learning set. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T06:40:23Z (GMT). No. of bitstreams: 1 ntu-103-R01849005-1.pdf: 650057 bytes, checksum: 28bdbd283a72b82ae68ca9346a361837 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 口試委員審定書 I
致謝 II 摘要 III Abstract IV Contents V List of Tables VII List of Figures VIII Chapter 1. Introduction 1 Chapter 2. Materials and Methods 4 2.1 Participants 4 2.2 Neurocognitive Assessment 4 2.3 Statistical Analysis 6 2.3.1 Genotyping and Quality Control (QC) 6 2.3.2 Genotype Imputation 6 2.3.3 Principal Component Analysis (PCA) of Neurocognitive performance Indices 7 2.3.4 QT Association Analysis 7 2.3.5 Polygenic Score Analysis 8 Chapter 3. Results 9 3.1 Demographic Data and Clinical Characteristics 9 3.2 PCA of Neurocognitive Performance Indices 9 3.3 Genetic Analysis of QT GWAS 10 3.4 Polygenic Score Analyses 11 Chapter 4. Discussion 12 References 15 | |
dc.language.iso | en | |
dc.title | 以全基因組關聯探討思覺失調症之神經認知功能缺損:多基因分數策略 | zh_TW |
dc.title | A Genome-wide Association Study of Neurocognitive Impairments in Schizophrenia: Polygenic Score Approach | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 郭柏秀(Po-Hsiu Kuo),劉智民(Chih-Min Liu),蕭朱杏(Chuhsing Kate Hsiao),賴文崧(Wen-Sung Lai) | |
dc.subject.keyword | 思覺失調症,全基因組關聯,內表型,認知功能缺損,多基因分數分析, | zh_TW |
dc.subject.keyword | schizophrenia,GWAS,endophenotype,cognitive impairment,polygenic score analysis, | en |
dc.relation.page | 32 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2014-07-30 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
顯示於系所單位: | 流行病學與預防醫學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-103-1.pdf 目前未授權公開取用 | 634.82 kB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。