Tesis sobre el tema "Association copy"
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Li, Yinglei. "Genetic Association Testing of Copy Number Variation". UKnowledge, 2014. http://uknowledge.uky.edu/statistics_etds/8.
Texto completoJiang, Wei. "Killer-cell immunoglobulin-like receptor gene copy number, haplotypes and disease association". Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607691.
Texto completoChen, Wanting. "Copy Number Variants in the human genome and their association with quantitative traits". Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5957.
Texto completoGiannoulatou, Eleni. "Single nucleotide polymorphism and copy number variant genotyping for genome wide association studies". Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543550.
Texto completoDe, Tisham. "Statistical approaches for copy number variation detection and association with complex human phenotypes". Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/45494.
Texto completoWong, Hoi-man Emily y 黃凱敏. "Genome-wide association analyses on complex diseases: from single-nucleotide polymorphism to copy numbervariation". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50534099.
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Psychiatry
Doctoral
Doctor of Philosophy
Godoy, Thaís Fernanda. "Inherited copy number variation in the chicken genome and association with breast muscle traits". Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/11/11139/tde-26072018-112650/.
Texto completoA variação de número de cópias (CNV) é um polimorfismo importante que está associado a uma ampla gama de características em seres humanos, espécies selvagens e domésticas. Em frango, que é uma importante fonte de proteína e considerado um modelo biológico, CNVs foram associados a vários fenótipos e passos evolutivos. No entanto, nenhum estudo foi realizado para a identificação e caracterização da herança da CNV no genoma da galinha. Identificamos as CNVs no genoma da galinha usando duas populações experimentais e com pedigree conhecido: uma população de frangos de corte e uma F2. Em 826 frangos de corte, identificamos 25.819 CNVs (4.299 deleções e 21.520 duplicações), dos quais 21.077 foram herdados, 201 não foram herdados e 4.541 foram CNVs denominados de novo. Em 514 animais F2, identificamos 21.796 CNVs (2.254 deleções e 19.543 duplicações) das quais 18.230 foram herdadas, 587 não foram herdadas e 2.979 foram de novo CNVs. Após a etapa de filtragem nos de novo CNVs, apenas 220 (4,84%) e 430 (14,43%) permaneceram nas populações de frango de corte e F2, respectivamente. Um total de 33,11% (50 de 151) das CNV identificadas por dados de genotipagem em dez animais foram validados por dados de sequenciamento. Dos validados, 64% tinham mais de 80% do tamanho (pb) validados. Um total de 59% e 48,8% foram classificados como novas regiões de CNVs (CNVRs) nas populações de frango de corte e F2, respectivamente. Considerando os p-values corrigidos por Bonferroni para testes múltiplos e estatisticamente significativos (≤ 0,01), encontramos dois segmentos de CNV significativamente associados ao peso do peito, um ao rendimento de peso de peito, seis ao peso de carne de peito, 18 ao rendimento de carne de peito, quatro ao peso de filé de peito e dois ao rendimento do filé de peito. Esses segmentos de CNV significativamente associados estão sobrepostos com 181 genes codificadores de proteínas. O CNVseg 300, que foi associado a todas as características e abrange seis CNVRs, foram sobrepostos a um total de 26 genes codificadores de proteínas. Entre estes genes, o gene MYL1 (Myosin Light Chain 1) é expresso nas fibras rápidas do músculo esquelético, e os genes MLPH (Melanophilin), PRLH (Prolactin Releasing Hormone) e RAB17 (Member RAS Oncogene Family), que foram anteiromente associados ao fenótipo de cor azul acinzentado de penas e à regulação da homeotermia e do metabolismo. O presente estudo melhora o conhecimento sobre CNVs no genoma de frango, especialmente sobre a distribuição de CNV herdadas, não herdadas e de novo, em duas populações experimentais de frango. Além disso, a associação genômica foi a primeira realizada na população de frangos de corte com características do músculo do peito, que são muito importantes para a avicultura. Os resultados do GWAS nos permitem compreender a provável relação entre alguns genes e CNVRs que foram significativamente associados às características do músculo do peito.
Cifola, I. "Association of genome-wide DNA copy number data and transcriptional profile in renal carcinoma". Doctoral thesis, Università degli Studi di Milano, 2006. http://hdl.handle.net/2434/31123.
Texto completoLi, Zhiwei. "Characterising copy number polymorphisms using next generation sequencing data". Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-386050.
Texto completoJarick, Ivonne [Verfasser] y Helmut [Akademischer Betreuer] Schäfer. "Strategies for Genome-Wide Association Analyses of Raw Copy Number Variation Data / Ivonne Jarick. Betreuer: Helmut Schäfer". Marburg : Philipps-Universität Marburg, 2013. http://d-nb.info/1045729884/34.
Texto completoCharoen, Pimphen. "Robust approaches for performing meta-analysis of genome-wide association studies to identify single nucleotide polymorphisms and copy number variations associated with complex traits". Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/30165.
Texto completoSulovari, Arvis. "Integrating Human Population Genetics And Genomics To Elucidate The Etiology Of Brain Disorders". ScholarWorks @ UVM, 2017. http://scholarworks.uvm.edu/graddis/781.
Texto completoMarenne, Gaëlle. "Statistical Methods to Combine SPN and CNV Information in Genome-Wide Association Studies : An Application to Bladder Cancer". Thesis, Paris 11, 2012. http://www.theses.fr/2012PA11T046.
Texto completoCopy number variations (CNVs) are losses or gains of DNA sequences that may play a role in specific disease susceptibility. CNVs can be detected by high-resolution SNP-arrays through the analysis of allele intensities with CNV calling algorithms such as CNVpartition, PennCNV and QuantiSNP. In this thesis, we identified and assessed the performances of available tools for CNV calling and for association testing, at the genome-wide level. We also investigatedassociation strategies that combine information on both the allele and the number of copies for SNPs located in CNV regions. We applied these tools to conduct a genome-wide association study with CNV using data from the Spanish Bladder Cancer (SBC)/EPICURO Study generated by the Illumina 1M SNP-array. Our results showed a low reliability and a low sensitivity of the investigated CNV calling algorithms applied to SNP-array data. The GSTM1 locus shows a very frequent CNV that is associated with bladder cancer (BC) risk. We reported that the calling algorithms performed very poorly in identifying this CNV. We proposed using allele intensity measures (LRR) as a screening step to assess association as it allowed the detection of the GSTM1 CNV association with BC. To combine the allele and the number of copies for SNPs located in CNV regions, we investigated several strategies of association testing and we showed that the more powerfulone used a two-term model with the sum and the difference of the number of copies of both alleles. Finally, by applying these strategies to the (SBC)/EPICURO Study, we identified CNV regions potentially associated with BC risk, as well as SNPs for which both the allele and the number of copies could be involved in BC risk
Peterson, Roseann. "On the genetic and environmental associations between body composition, depression symptoms and smoking behavior". VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2889.
Texto completoPiazzon, Flavia Balbo. "Investigação clínica e citogenética molecular em pacientes com atraso de desenvolvimento neuropsicomotor associado à malformação congênita". Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5144/tde-24032016-145538/.
Texto completoIntroduction: The recent technological advances on DNA-based techniques have established in modern medicine good opportunities to elucidate undefined clinical cases in patients with complex chromosomal microrearrangements. The performance of MLPA (Multiplex ligation-dependent probe amplification) technique together with array technologies (WGAS - whole genome array screening) created the possibility of one single experiment to analyze different regions of interest in the human genome. Objective: Patients with psychomotor delay (PSMD) associated with multiple congenital anomalies who had normal or inconclusive G-band-karyotype (MCA) were studied in order to understand the genotype-phenotype correlations. Material and methods: This study involved 71 patients with psychomotor delay (PSMD) associated with multiple congenital anomalies (MCA) analyzed by MLPA (P036 and P064 kits), followed by WGAS different platforms (Agilent, Affymetrix e Illumina®). Results: Among 33 patients with pathogenic and uncertain (VOUS) copy number variations (CNV) were found: 12 deletions, 5 duplications and 16 concomitant duplication and deletion (dup/del). There were 29 patients with conclusive pathogenic findings, 4 patients with VOUS and 16 patients with normal array, but others 23 patients with benign results, which means there is no gene content in the region involved, or because these genes were not linked to phenotype, or even due to CNVs inherited of healthy parents. From the whole casuistic, 4 individuals presented loss of heterozygosity (LOH) regions. Conclusions: The use of a combined strategy of analysis (MLPA - WGAS) with a high capacity to detect pathogenic CNVs allows unraveling microscopic imbalances, and consequently, offers an adequate clinical correlation for patients not previously diagnosed by classical cytogenetics. In conclusion, this study suggests a new model for the combined application of these techniques, which represents an optimal alternative for a genomic screening and diagnostic establishment in patients with rare complex disorders and their families
Marengo, Graciela Emilia Silva. "Association between asthma and COPD: A longitudinal evaluation of the Dutch hypothesis". Diss., The University of Arizona, 2004. http://hdl.handle.net/10150/289241.
Texto completoMitchell, Colin. "The Association Between Exhaled Nitric Oxide in Exhaled Breath Condensate and Chronic Obstructive Pulmonary Disease". ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/397.
Texto completoMcPhee, Kelly. "A preliminary investigation into the association between Chronic Obstructive Pulmonary Disease (COPD) and oropharyngeal dysphagia, and its impact on health". Thesis, University of Sheffield, 2011. http://etheses.whiterose.ac.uk/1593/.
Texto completoAndersson, Anthon y Robin Guntell. "Advancing the COO Construct From an Affective Dimension : The Application of Projective Technique". Thesis, Linnéuniversitetet, Institutionen för marknadsföring (MF), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-47045.
Texto completoGaytan, Monika. "The association of dust events with asthma exacerbation in the U.S.-Mexico Border children". To access this resource online via ProQuest Dissertations and Theses @ UTEP, 2009. http://0-proquest.umi.com.lib.utep.edu/login?COPT=REJTPTU0YmImSU5UPTAmVkVSPTI=&clientId=2515.
Texto completoAmorim, Adriana Silva. "A Experiência Trágica do Torcedor Brasileiro: Análise da Copa do Mundo de Futebol de 1950 enquanto Unidade Dramática". Escola de Teatro, 2015. http://repositorio.ufba.br/ri/handle/ri/27003.
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RESUMO A presente tese apresenta os resultados da pesquisa de caráter predominantemente bibliográfico, cujo principal objetivo foi investigar as características formais e conceituais do futebol que tornassem possível afirmar que, na relação com o esporte em questão, o torcedor brasileiro vivencia uma verdadeira experiência trágica, conforme configurada nos termos poéticos, expressos a partir de elementos relacionados à sua forma, e nos termos teóricos, com base nos elementos relacionados a tal experiência do ponto de vista filosófico. Para tanto, foram investigados os diversos modos de compreensão do conceito de “tragédia” e de “trágico”, a partir da literatura dramática e da literatura filosófica que apresentam investigações sobre o tema, ancoradas, respectivamente, em Aristóteles e Friedrich Nietzsche. Além disso, foram construídos conceitos próprios e originais inspirados por uma lógica dramatúrgica, testados no objeto escolhido, qual seja, a Copa do Mundo de Futebol de 1950, realizada no Brasil, focando mais especificamente na última partida que foi disputada pelas seleções do Brasil e do Uruguai.
ABSTRACT This thesis presents the results of predominantly bibliographical research, which main objective was to investigate the formal and conceptual characteristics of football association (soccer) that would make possible to say that through the relationship with the sport in question, the Brazilian fan lives through a true tragic experience as configured in terms poetic expressed from elements related to its form, and a theoretically based on the information related to the experience from a philosophical point of view. Thereunto, different ways of understanding the concept of “tragedy” and “tragic” were investigated, from the dramatic literature and philosophical literature presenting research on the subject, anchored respectively in Aristotle and Friedrich Nietzsche. In addition, original and own concepts were built inspired by a dramaturgical logic tested in the chosen object, namely, the Football World Cup 1950, held in Brazil, focusing more specifically in the last match that was played between Brazilian’s and Uruguay’s teams.
Jia, Ning. "Security analyst behavior and the association with pre-ipo equity investments and under writing by investment banks /". May be available electronically:, 2007. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
Texto completoPatel, Kantibhai Motiram. "The association of the human leukocyte antigens alleles and type 2 diabetes mellitus among Mexican Americans". To access this resource online via ProQuest Dissertations and Theses @ UTEP, 2009. http://0-proquest.umi.com.lib.utep.edu/login?COPT=REJTPTU0YmImSU5UPTAmVkVSPTI=&clientId=2515.
Texto completoBurgos-Monzon, Ximena. "Association of overweight and obesity with inflammation and blood pressure in U.S.-Mexico Border elementary school children". To access this resource online via ProQuest Dissertations and Theses @ UTEP, 2008. http://0-proquest.umi.com.lib.utep.edu/login?COPT=REJTPTU0YmImSU5UPTAmVkVSPTI=&clientId=2515.
Texto completoMelro, Hélder Filipe Fernandes. "Contributions for unravelling chronic obstructive pulmonary disease trajectory: associations between genetics and clinical measures". Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/21403.
Texto completoChronic Obstructive Pulmonary Disease (COPD) is a multifactorial and heterogeneous disease which impacts differently on patients with similar grades. This suggests that factor others than lung function may affect patients experience of the disease. Patient-reported outcomes (PROs) are a set of measures that allow to assess patients’ self-perception and experience of the disease. Recent studies have reported associations between specific single nucleotide polymorphisms (SNPs) and PROs, however not much is known about these associations and their meanings. Thus, this study had as main objective to explore possible associations between specific genetic variants and clinical measures, including PROs. It also sought to contribute for a characterization of the genotypes from patients with COPD in Portugal. A cross-sectional study was conducted in a total number of 60 patients with COPD. The PROs assessed were: 1) self-reported frequency of exacerbations, 2) dyspnoea with modified Medical Research Council and Borg scales , 3) fatigue with Borg scale, 4) anxiety and depression with Hospital Anxiety and Depression scale; 5) impact of the disease with COPD Assessment Test and 6) health-related quality of life (HRQOL) with St. George Respiratory questionnaire; Additionally, several surrogate outcomes were also assessed i. e., lung function, peripheral muscle strength with digital dynamometer, respiratory muscle strength with the respiratory pressure assessment and functional capacity through the 1 minute and 5 time sit-to-stand. Both oropharyngeal swabs and saliva samples were collected from the patients for genotyping. Significant associations were found between genetic variants and dyspnoea (rs1143634, rs1042717, rs1138272 and rs12504628), fatigue (rs1042714, rs1138272), anxiety (rs1051303, rs1800450 and rs1131620), impact of the disease (rs10461985 and rs11172113) and HRQOL (rs11172113, rs1042713, rs1138272 and rs12504628). Significant associations were also found between genetic variants and lung function (rs1042713, rs1042717, rs5030737), respiratory muscle strength (rs1130866), peripheral muscle strength (rs1042713, rs1042717, rs11172113, rs11556218) and functional capacity (rs12899618, rs11046966 and rs1138272). This was an exploratory study and more investigations are necessary to confirm the results obtained and to explore deeply the associations and interpretations between genetics and COPD trajectory.
A Doença Pulmonar Obstrutiva Crónica (DPOC) é uma doença multifatorial e heterogénea que apresenta impactos diferentes em pacientes com estadios da doença semelhantes. Isto sugere que outros fatores para além da função pulmonar podem afetar a forma como o paciente experiencia a sua doença. As medidas reportadas pelo paciente (PROs) são um conjunto de variáveis que permitem avaliar a autoperceção e experiência dos doentes em relação à sua doença. Estudos recentes reportaram a existência de associações entre polimorfismos de nucleótidos simples (SNPs) e PROs, mas pouco ainda se sabe sobre estas associações e seu significado. Assim, este estudo teve como objetivo principal explorar possíveis associações entre variantes genéticas específicas e medidas clínicas, entre as quais PROs. Pretendeu também contribuir para a caracterização dos genótipos dos doentes com DPOC em Portugal. Realizou-se um estudo transversal com 60 doentes com DPOC. As PROs avaliadas foram 1) frequência de exacerbações autoreportadas pelos doentes, 2) dispneia com a modified medical Research Council Scale e Borg, 3) fadiga com a Borg, 4) ansiedade e depressão através da escala de ansiedade e depressão hospitalar, 5) impacto da doença com o teste de avaliação da DPOC e 6) qualidade de vida relacionada com a saúde (QVRS) com questionário do hospital de St. George na doença respiratória. Adicionalmente, outras medidas clínicas também foram avaliadas, i. é., função pulmonar, força muscular periférica com dinamometria digital, força dos músculos respiratórios com a medição das pressões respiratórias e capacidade funcional através do teste de levantar e sentar cinco vezes e 1 minuto. Zaragatoas orofaríngeas e amostras de saliva foram recolhidas de todos os pacientes para genotipagem. Foram encontradas associações significativas entre variantes genéticas e dispneia (rs1143634, rs1042717, rs1138272 e rs12504628), fadiga (rs1042714 e rs1138272), ansiedade (rs1051303, rs1800450 e rs1131620), impacto da doença (rs10461985 e rs1172113) e QVRS (rs11172113, rs1042713, rs1138272 e rs12504628). Também foram encontradas variantes significativamente associadas à função pulmonar (rs1042713, rs1042717 e rs5030737), força dos músculos respiratórios (rs1130866), força muscular periférica (rs1042713, rs1042717, rs11172113 e rs11556218) e capacidade funcional (rs12899618, rs11046966 e rs1138272). Este foi um estudo exploratório e mais investigações são necessárias para confirmar os resultados obtidos e para explorar mais profundamente a associação e interpretação entre a genética e a trajetória da DPOC.
Herber-Valdez, Christiane R. "Understanding a Hispanic serving institution beyond the federal definition a qualitative analysis of Mexican American student perceptions and experiences /". To access this resource online via ProQuest Dissertations and Theses @ UTEP, 2008. http://0-proquest.umi.com.lib.utep.edu/login?COPT=REJTPTU0YmImSU5UPTAmVkVSPTI=&clientId=2515.
Texto completoTecklenburg, Gerhard. "Design of body assemblies with distributed tasks under the support of parametric associative design (PAD)". Thesis, University of Hertfordshire, 2011. http://hdl.handle.net/2299/5809.
Texto completoDaly, Marwa El. "Challenges and potentials of channeling local philanthropy towards development and aocial justice and the role of waqf (Islamic and Arab-civic endowments) in building community foundations". Doctoral thesis, Humboldt-Universität zu Berlin, Philosophische Fakultät III, 2012. http://dx.doi.org/10.18452/16511.
Texto completoThis work provides a solid theoretical base on philanthropy, religious giving (Islamic zakat, ‘ushour, Waqf -plural: awqaf-, Sadaqa and Christian tithes or ‘ushour), and their implications on giving trends, development work, social justice philanthropy. The field study (quantitative and qualitative) that supports the theoretical framework reflects at a national level the Egyptian public’s perceptions on philanthropy, social justice, human rights, giving and volunteering and other concepts that determine the peoples’ civic engagement. The statistics cover 2000 households, 200 Civil Society Organizations distributed all over Egypt and interviews donors, recipients, religious people and other stakeholders. The numbers reflect philanthropic trends and for the first time provide a monetary estimate of local philanthropy of over USD 1 Billion annually. The survey proves that the per capita share of philanthropy outweighs the per capita share of foreign economic assistance to Egypt, which implies the significance of local giving if properly channeled, and not as it is actually consumed in the vicious circle of ad-hoc, person to person charity. In addition, the study relates local giving mechanisms derived from religion and culture to modern actual structures, like community foundations or community waqf that could bring about sustainable change in the communities. In sum, the work provides a comprehensive scientific base to help understand- and build on local philanthropy in Egypt. It explores the role that local individual giving could play in achieving sustainable development and building a new wave of community foundations not only in Egypt but in the Arab region at large. As a tangible result of this thesis, an innovative model that revives the concept of waqf and builds on the study’s results was created by the researcher and a dedicated board of trustees who succeeded in establishing Waqfeyat al Maadi Community Foundation (WMCF) that not only introduces the community foundation model to Egypt, but revives and modernizes the waqf as a practical authentic philanthropic structure.
Houle, Emily. "The Association Between Sperm DNA Methylation and Sperm Mitochondrial DNA Copy Number". 2020. https://scholarworks.umass.edu/masters_theses_2/950.
Texto completoHUANG, LI-YU y 黃俐瑜. "Combined Testing for Association Study of Copy Number Variation in Next Generation Sequencing". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/56t225.
Texto completo逢甲大學
統計學系統計與精算碩士班
106
Copy number variation (CNV) is a kind of genetic variation with abnormal fragment copies. Comparative the sequencings between case and control groups could detect the disease associated with CNVs. In this research, we focus on a specific issue about combining test statistics in the CNV association study. The absolute copy number for each window between case and control groups are compared, and then the test statistics are combined to identify the significant disease associated CNVs. The corresponded statistical methods are evaluated via simulation studies.
YU-RULiao y 廖鈺茹. "Modeling Association between DNA Copy Number and RNA Expressions on Colon Adenocarcinoma Patients". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/56pnpu.
Texto completoChang, Cheng-Chen y 張正辰. "The Association of Leukocyte Mitochondrial DNA Copy Number, Polymorphisms, and Oxidative Damage in Affective Disorders". Thesis, 2016. http://ndltd.ncl.edu.tw/handle/95557373165035584916.
Texto completo中山醫學大學
醫學研究所
104
Aims: This dissertation consists of two parts: (1) To compare alterations of mitochondria DNA (mtDNA) copy number, single nucleotide polymorphisms (SNPs), and oxidative damage of mtDNA in clinically stable patients with bipolar I disorder (BD) and normal controls. (2) The same research topics were investigated between patients of major depressive disorder (MDD) and normal controls. Methods: Patients met DSM-IV diagnostic criteria for BD and MDD were recruited from the psychiatric outpatient clinic at a medical center in Central Taiwan. They were clinically stable and their medications had not changed for at least the preceding two months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. All participants had no history of chronic medical illness, no indication of acute infection and were not pregnant. Comparison subjects did not have any history of major psychiatric disorders and they were non-smokers. By analyzing peripheral blood leukocytes, copy number, SNPs and oxidative damage of mtDNA were compared between patients and controls. Results: Forty BD patients, 40 MDD patients and 70 comparison subjects were included in this study. The median age of the subjects was 42, 41.5 and 38 years in MDD, BD and comparison groups, respectively. Leukocyte mtDNA copy number was significantly lower in BD and MDD patients than that of the comparison group (p<0.001 and p=0.037). All patients had significantly higher mitochondrial oxidative damage than the comparison group. The SNP of mtDNA C5178A and A10398G were similar in patients and control groups. After generalized linear model adjusting with related variables, mtDNA copy number was still significantly lower both in BD (p<0.001) and MDD group (p<0.001). MtDNA oxidative damage was positively correlated with age. Antipsychotic use was negatively associated with mtDNA copy number (p=0.036) in MDD group. Conclusions and Suggestions: Possible involvement of oxidative damage and mitochondria in the pathophysiology of BD and MDD needs more large-scale studies. Future study of mitochondrial dysfunction in affective disorders may bring some light in the development of disease biomarker. The study is cross-sectional with no longitudinal follow up. This relationship between mitochondrial dysfunction and affective disorders was correlational instead of causal. The study cohort is clinically stable and generalizability of our result to other cohort should be cautiously considered.
Chiang, Kuang-Mao y 姜廣茂. "Genome-Wide Association Studies with Single Nucleotide Polymorphisms (SNPs), Copy Number Variations (CNVs), and Gene Expression Profiles to Find Genetic Markers for Young-Onset Hypertension in Taiwan Han Chinese". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/jehx3x.
Texto completo國防醫學院
生命科學研究所
102
Hypertension is an important public health problem in Taiwan and in the world. Although many large-scale genome-wide association studies (GWAS) have been performed, few study identified replicable and large-impact hypertension loci, not to mention the scanty Chinese studies. Young onset hypertension (YOH) is considered as a more promising target disorder to investigate than the late-onset one due to its stronger genetic component. To map YOH genetic variants, we carried out GWAS to search for hypertension susceptibility loci/genes with whole genome SNPs, CNVs and gene expression profiles. This investigation was consisted of 3 studies. The first part is a three-stage genome-wide association study using SNPs as genetic markers (SNPs-GWAS), combining 1st-stage multilocus GWAS (400 age- and sex-matched pairs), 2nd-stage gene expression analysis, and 3rd-stage multilocus confirmatory study (992 matched pairs). The second part is a two-stage genome-wide CNVs association study (CNVs-GWAS) consisting of an usual first stage GWAS (200 matched pairs) to find potential susceptibility CNV regions and a second stage confirmatory association study with an independent set of samples (199 matched pairs). Gene expression profiles were used to find differentially expressed genes among those implicated in both the first and second stages of the study. The third part is a two-stage genome-wide gene expression association study (GEs-GWAS), consisting of a regular GWAS in the 1st - stage (126 YOHs and 149 controls) to find the differentially expressed genes and a further confirmation with an independent set of samples (127 YOHs and 150 controls). We also integrated the gene expression data and SNP data to find eSNPs. In the SNPs-GWAS, a total of six SNP septets flanking the C1orf135, GSN, LARS, and ACTN4 remained significant in all three stages. Among them, the septet flanking ACTN4 and LARS was also associated with blood pressure/hypertension in two external replication studies: Hong Kong Hypertension Study (HKHS) and WTCCC hypertension study. In the CNVs-GWAS, 11 CNVs regions involving 14 genes were identified. In the GEs-GWAS, 9 genes were significantly associated with hypertension in both the first- and second-stage. Among these genes, ZRANB1, FAM110A, PREP, ANKRD9 and LAM2 were also differentially expressed in an existing database of hypertensive mouse model (GSE19817). Our study identified several previously unknown YOH loci/genes in Han Chinese. Identification of these genes enriches hypertension susceptibility gene list, thereby shedding light on the etiology of hypertension in Han Chinese.
Ivanga, Mahiné. "Étude pangénomique de la variabilité dans le nombre de copies liée à l’hypertension artérielle et ses anomalies métaboliques associées". Thèse, 2014. http://hdl.handle.net/1866/10532.
Texto completoEssential hypertension (HT) is a multifactorial complex disease with a strong genetic component. However, little is known about the effects of copy number variance on HT. We hypothesized common Copy Number Variants (CNVs) could increase or decrease the risk for HT. We performed GWAS of CNVs with HT and, with HT and Type 2 Diabetes (T2D), in 21 families of the Saguenay-Lac-St-Jean region of Quebec (FC) affected by early-onset hypertension and dyslipidemia. Replication was tested in a cohort of 3349 unrelated diabetic subjects of Caucasian origin from the ADVANCE trial. Replication was also tested in 187 individuals from the Czech Post-Monica (CPM) cross-sectional survey, ascertained by the presence/absence of albuminuria and/or metabolic syndrome. We performed locus-specific transcriptional analyses in 134 subjects from the CARTaGENE population cohort. We identified two CNV Regions (CNVRs), at 17q21.31, associated with HT and T2D in FC and associated with hypertension in ADVANCE diabetics. A statistical model of association including both CNVRs underlined the main effect size of CNVR1 on insulin resistance, T2D early onset and duration, and risk for cardiovascular diseases (CVD). CNVR1 appeared to influence LOC644172 expression, whose transcript abundance was associated with the prevalence of HT and T2D, and strongly with the risk of CVD and vascular age (P<2×10-16). Our results suggest carriers of copy-number gain at these 17q21.31 loci, principally at the CNVR1 locus, undergo premature β-cell functional deregulation and insulin resistance, due to increase dosage of the LOC644172 pseudogene, which might in turn affect the regulation of expression of its functional paralog, MAPK8IP1. We also report six different CNVR loci, highly heritable and contributing to the risk of hypertension, in French Canadians. The combined CNV risk score appeared robustly related to prevalence of hypertension (p=2×10-10) and age at diagnosis of hypertension. In FC, this combined CNV risk score model showed a C-statistic of 0.71 for HT and appeared as powerful as Framingham HT risk score in predicting hypertension in individuals aged less than 25. We validated the association of a new locus, 19q13.12 deletion-CNVR, with hypertension, in CPM. FFAR3 surrounds this 19q13.12 deletion-CNVR. It has been demonstrated that in mice, a portion of propionate hypotensive effect is mediated by Ffar3, and involves a cross-talk between the gut microbiota and the renal-cardiovascular system. The identified CNVRs appear to influence genes and QTLs mainly related to immune and inflammatory responses and renal damaged and repair. Some CNVRs are exclusive to primates. This study suggests that additive and interactive actions of multiple copy-number variants are involved in the etiology of hypertension or of hypertension associated with T2D.
Girard, Simon L. "Étude sur le rôle des déséquilibres génomiques dans le Syndrome d’Impatiences Musculaires de l’Éveil". Thèse, 2010. http://hdl.handle.net/1866/4115.
Texto completoRestless Legs syndrome (RLS) is a neurological disorder characterized by the urge to move one’s limbs. It is also one of the most frequent causes of insomnia. The prevalence of RLS is estimated to be around 15% in the general population. Complexes disorders like RLS are often the result of the evolution of genetic and environmental components. For RLS, recent Genome Wide Association Study (GWAS) have identified four variants with mild to moderate effects. However, those four variants explain only a small part of the disease heritability and thus, we expect that many new variants are still to be found. The impact of Copy-Number Variation (CNV) in the genetic mechanism of RLS is still unknown. However, many studies have recently position the CNVs as a significant source of genetic variation potentially responsible of phenotypes. In collaboration with a team from Munich, we conducted two genome-wide CNVs studies (Genome Wide SNP chips and Comparative Genomic Hybridization (CGH)) on RLS patients from Germany. Using cases-controls studies, we identified regions with a different occurrence of CNVs for RLS patients, compared to different groups of controls. One of these regions is particularly interesting, as it has already been identified by both linkage and association studies.
Tien, Hong-Yih y 田鴻毅. "Association study of serum growth factors in patient with COPD". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/a9evkc.
Texto completo國立臺灣大學
臨床醫學研究所
107
Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by complex inflammatory, neuronal and fibrotic changes. Growth factor plays a key regulator of neuronal plasticity, and a crucial role in tissue repair and emphysema pathogenesis. The aims of this study was to determine which blood-based molecules (growth factors) have been evaluated as possible biomarkers to diagnose outcome of chronic obstructive pulmonary disease (COPD), to be correlated with lung function of forced expiratory volume in one second (FEV1% of predicted), and to predict risk of acute exacerbations. Methods: In the present study, patients over 40 and under 100 years of age with COPD (spirometry GOLD stages 1–4) were studied. Lung function, smoking history, medication, eosinophil of peripheral blood and serum concentrations of growth factors were assessed in all participants. There were 11 kinds of growth factors in this study, including NGF(Nerve growth factor-beta), BDNF(Brain-derived neurotrophic factor), EGF(Epidermal growth factor), FGF-2 (fibroblast growth factor-2), HGF( Hepatocyte growth factor), LIF(Leukemia inhibitory factor), PDGF (Platelet-derived growth factor), PLGF Placental growth factor), SCF(Stem cell Factor), VEGF-A and VEGF-D(Vascular endothelial growth factor-D). Spearman rank correlation was used to assess the relationship between growth factors and FEV1 predicted levels. The trend of levels of growth factors across COPD severity (GOLD grading or ABCD group classification) was assessed by the Jonckheere-Terpstra test. We also compared levels of growth factors between subgroups of FEV1% of predicted (< 50% vs. ≥ 50%), eosinophil (≥ 2% vs. < 2%), and frequent acute exacerbation (AE) in the previous year (0-1 vs. 2-3) by the Mann-Whitney U-test. The associations between growth factors and binary outcomes (e.g., GOLD grading 3-4, FEV1% of predicted <50%) were determined using multivariable logistic regression analysis with adjustment with sex, age, smoking status and body mass index. The performance of growth factors to discriminate frequent AE was evaluated by Receiver Operating Characteristic (ROC) curve analysis. The validation using outcome in the next year was also performed. Results: A total of 138 participants were enrolled who male is predominant (98.6%) and with a mean age of 68.3 years (standard deviation [SD], 9 years). The mean FEV1 predicted levels were 55.7% (SD, 18.4%). Number of GOLD stages 1–4 was 16 (11.6%), 67 (48.6%), 45 (32.6%) and 10 (7.2%) respectively. Number of COPD group classification A, B, C and D was 58 (42.0%), 28 (20.3%), 30 (21.7%), and 22 (15.9%) respectively. No significant correlation between the 11 growth factors and FEV1 predicted levels was found. There were no significant trend of levels of the 11 growth factors across GOLD grading or COPD group classification. There were no significant difference in levels of the 11 growth factors between subgroup of FEV1 predicted (< 50% vs. ≥ 50%) and eosinophil (≥ 2% vs. < 2%). Notably, serum levels of both FGF-2 and VEGF-D were significantly decreased in patients with frequency of acute exacerbations of COPD (AECOPD) compared with patients with infrequency of AECOPD (both P < 0.05) in previous year. The ROC curves showed the area under the curve (AUC) of FGF-2 was 0.704 (95% confidence interval [CI], 0.620 to 0.778, P = 0.010), the optimum cut point for Youden index was ≤4.76 with a sensitivity of 81.8% and a specificity of 62.2%. Another AUC of VEGF-D was 0.700 (95% CI, 0.616 to 0.775, P = 0.004), its Youden index is optimally ≤10.02 with a sensitivity of 100% and a specificity of 43.3%. After combining FGF-2 and VEGF-D in the logistic regression, the result showed that the AUC was 0.777 (95% CI, 0.697 to 0.844, P < 0.001). A total of 112 participants were enrolled for validation study in the next year. Higher FGF-2 level was associated with a lower risk of acute exacerbations of COPD one year later (odds ratio, 0.972; 95% CI, 0.949-0.997). The ROC curves showed the area under the curve (AUC) of FGF-2 was 0.614 (95% CI, 0.518 to 0.705, P = 0.032), the optimum cut point for Youden index was ≤9.12. Higher NGF was associated with a lower risk of frequent AE of COPD one year later(odds ratio, 0.93; 95% CI, 0.87-0.99).Similarly, using the ROC curve, the AUC of the NGF was 0.797 (P < 0.001), which reached an acceptable discriminating power for predict of frequency of acute exacerbations of COPD, the optimum cut point for the Younden index is ≤ 25.23. Conclusion: FGF-2 and VEGF-D concentrations are associated with increased frequency of acute exacerbations of COPD in previous year. FGF-2 was used to predict acute exacerbation of COPD after one year later. For predicting acute exacerbation, if combined with other growth factors (eg, FGF-2, VEGF-D, NGF, etc.), the prediction sensitivity should be improved. Therefore, measuring serum VEGF-D, FGF-2 and NGF concentrations in patients with COPD should be a sensitive indicator for predictive acute exacerbation of patients. Therefore, this may be used as a biomarker for COPD.
Olmsted, Alexandra. "Sperm Mitochondrial Copy Number and Associations with Oxidative Stress and Phthalate Metabolites in Male Partners Undergoing Assisted Reproductive Technologies". 2017. https://scholarworks.umass.edu/masters_theses_2/547.
Texto completoLO, PRESTI Anna Rita. "CANDIDATE GENE ASSOCIATION ANALYSIS IN RESPIRATORY DISEASES – THE GEIRD PROJECT". Doctoral thesis, 2012. http://hdl.handle.net/11562/393934.
Texto completoAsthma, Rhinitis and Chronic Obstructive Pulmonary Disease (COPD) are common respiratory diseases worldwide, characterized by systemic and local chronic inflammation of the airways and increasing bronchial responsiveness, that contribute substantially to morbidity and mortality in adults living in the developed world. They are complex and heterogeneous diseases resulting from interaction between genetic and environmental factors. Several genes, each with a small effect, are likely involved in the development of these diseases and might contribute to the phenotype variability according to environmental exposure. Many candidate genes are reported in the literature data in association to one, two or all three diseases, even if results of these studies are not always consistent. This work is a part of the GEIRD (Gene Environment Interaction Respiratory Diseases) project, a population-based case-control study, aimed to elucidate the role of environment and genetic factors in the occurrence, persistence, severity and control of inflammatory airway diseases. In particular, the PhD thesis project here presented is focused on candidate gene association analysis in a large and accurately defined series of Italian subjects, in order to identify genes involved in the susceptibility to Asthma, Rhinitis and COPD and susceptibility genes that may be common to all the three diseases. A total of 1175 individuals, including subjects affected by asthma, rhinitis and COPD (cases) and unaffected by airways inflammatory diseases (controls), have been enrolled. A DNA bank, from all the subjects participating to the study, was created. Candidate genes for the study was chosen on the basis of the analysis of literature data, considering single genes studies, GWAS and meta-analyses. A group of 69 genes, involved in pathways related to the all three studied diseases, as inflammation, innate immunity and immunoregulation, oxidative stress and metabolism of xenobiotics, regulation of the protease-antiprotease equilibrium, and tissue remodelling, were selected. A panel of 384 Tag SNPs, representative of the candidate genes, was genotyped by a customized multiplexed GoldenGate Genotyping assay (Illumina). A single-locus and multi-locus association analysis was conducted to evaluate association with the following phenotypes: current asthma, past asthma, total asthma (current and past), current atopic asthma, allergic rhinitis, non allergic rhinitis, total rhinitis (allergic and non allergic), and subjects presenting with chronic respiratory symptoms. A significant association (p<0,01) was observed between IL-13 (5q31) and past asthma, both SPINK-5 (5q31-q32) and GSTP-1 (11q13) and non-atopic rhinitis, NOS-1 (12q24.2-24.31) and chronic respiratory symptoms. More interestingly, polymorphisms in IL1RL-2 gene (2q12) were found associated to multiple phenotypes (current asthma, current atopic asthma, chronic respiratory symptoms, non atopic rhinitis, and total rhinitis) suggesting a possible role for this gene in all the studied respiratory diseases. Therefore, we decide to deepen the study performing an haplotype association analysis for these genes. This additional study confirmed the single-locus associations found and the involvement of IL-13, SPINK-5, GSTP-1, NOS-1 and IL1RL-2 genes in the susceptibility to inflammatory respiratory diseases. The results of this study can be used in the future for the development of new molecular genetic tests for the early identification of subgroups of patients who need a specific therapy or having an individual susceptibility to specific environmental risk factors, by the determination of their genetic risk profile. In the post-genomic era, searching and identification of genes associated with complex diseases are still one of the main challenges for dissecting human complex diseases. A better understanding of pathogenic mechanisms and the identification of molecular markers of disease and genomic profiles, associated to particular diseases phenotypes and clinical outcomes, will be offering new targets for pharmacological therapy and will be opening the way to possible future applications in disease treatment and prevention, by a more accurate prognosis determination and a more specific or even individual therapies.
Cheng, Yu-Chiao y 鄭宇喬. "The associations of serum IgE levels and blood eosinophil counts with COPD clinical features". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/2ar9ju.
Texto completo國立中山大學
生物科學系研究所
106
Background: Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the world, is a chronic inflammatory disease of the airway characterized by “persistent airflow limitation that is usually progressive”. COPD is recognized as a complex and heterogeneous syndrome. Significant heterogeneity exists within COPD with respect to clinical presentation, physiology, imaging, response to therapy, decline in lung function, and survival. Currently, there are neither consensus phenotypes classification nor useful biomarkers in COPD. Serum IgE and blood eosinophil, which are easy to measure, have been used as biomarkers in asthma. This study aimed to evaluate the clinical utility of serum IgE levels and blood eosinophil counts in COPD patients. Methods: We conducted a prospective observational study in Kaohsiung Medical University Hospital. From Jan 1, 2016 to Dec 31, 2017, we enrolled 208 patients with COPD into this study. These patients were followed till Mar 31, 2018, with a mean follow-up period of 18.8 months. Of the 208 enrolled patients, 190 with complete data were analyzed. We compared clinical features and exacerbation frequency between COPD patients with serum IgE < 100 KU/L vs. ≥ 100 KU/L, blood eosinophil counts < 300/µL vs. ≥ 300/µL and blood eosinophil < 4% vs. ≥ 4% Results: Of the 190 COPD patients analyzed in this study, 56 (29.5%) patients had moderate or severe acute exacerbation events, 55 (28.9%) had blood eosinophil ≥ 300/µL, 65 (34.2%) had blood eosinophil ≥ 4%, and 83 (45.1%) had serum IgE ≥ 100 KU/L. COPD patients with blood eosinophil ≥ 300/µL or > 4% had significantly higher risk of acute exacerbation (OR = 2.80, 95% CI = 1.44-5.44, P = 0.011; OR = 2.35, 95% CI = 1.23-4.48, P = 0.093). Serum IgE ≥ 100 KU/L were not associated with higher risk of acute exacerbation (OR = 0.81, 95% CI = 0.43-1.55, P = 0.533). In multivariate analysis, positive bronchodilator response, diffusion capacity of the lung for carbon monoxide (DLCO) and blood eosinophil percentage were significantly associated with acute exacerbation risk. For every 1% increment in blood eosinophil, the risk of exacerbation increased by 25% (OR = 1.25, 95% CI = 1.09-1.43, P = 0.001). Conclusion: Blood eosinophil count and percentage were significantly associated with acute exacerbation in COPD. For every 1% increment in blood eosinophil, the risk of exacerbation increased by 25%. Serum IgE levels were not associated with risk of COPD acute exacerbation. Blood eosinophil are easily available and can serve as useful biomarkers in COPD. We suggest measuring blood eosinophil counts or percentage routinely in COPD to evaluate the risk of future acute exacerbation.
Moreau, Clara. "Mapping genome-wide neuropsychiatric mutation effects on functional brain connectivity : c opy number variants delineate dimensions contributing to autism and schizophrenia". Thesis, 2020. http://hdl.handle.net/1866/24592.
Texto completoResearch on Autism Spectrum Disorder (ASD) and schizophrenia (SZ) has mainly adopted a ‘top-down’ approach, starting from psychiatric diagnosis, and moving to intermediate brain phenotypes and underlying genetic factors. Recent cross-disorder studies have raised questions about diagnostic boundaries and pleiotropic mechanisms. By contrast, the recruitment of groups based on the presence of a genetic risk factor allows for the investigation of molecular pathways related to a particular risk for neuropsychiatric conditions (NPs). Copy number variants (CNVs, loss or gain of a DNA segment), which confer high risk for NPs are natural candidates to conduct such bottom-up approaches. Because CNVs have a similar range of adverse effects on NPs, we hypothesized that entire classes of CNVs may converge upon shared connectivity dimensions contributing to mental illness. Resting-state functional MRI (rs-fMRI) studies have provided critical insight into the architecture of brain networks involved in NPs, but so far only a few studies have investigated networks modulated by CNVs. We aimed at 1) Delineating the effects of neuropsychiatric variants on functional connectivity (FC), 2) Investigating whether the alterations associated with CNVs are also found among idiopathic psychiatric populations, 3) Testing whether deletions reorganize FC along general dimensions, irrespective of their localization in the genome. We gathered rsfMRI data on 502 carriers of eight NP-CNVs (high-risk), four CNVs without prior association to NPs as well as carriers of eight scarcer NP-CNVs. We also analyzed 756 subjects with idiopathic ASD, SZ, and attention deficit hyperactivity disorder (ADHD), and 5,377 controls. Connectome-wide analyses showed a positive gene dosage effect for the 22q11.2 and 1q21.1 CNVs, and a negative association for the 16p11.2 CNV. The effect size of CNVs on relative FC (mean-connectivity adjusted) was correlated with the known level of NP-risk conferred by CNVs. Consistent with results on cognition, we also reported that deletions had a larger effect size on FC than duplications. We identified similarities between high-risk CNV profiles and the connectivity architecture of individuals with NPs. The level of similarity was associated with mutation severity and was strongest in SZ, followed by ASD, and ADHD. The similarity was driven by the thalamus, and the posterior cingulate cortex, previously identified as hubs in transdiagnostic psychiatric studies. These results raised questions about shared mechanisms across CNVs. By comparing deletions at the 16p11.2 and 22q11.2 loci, we identified similarities at the connectivity, and at the gene expression level. We extended this work by pooling all deletions available for analysis. We asked if connectivity alterations were associated with the severity of deletions scored using pLI, a measure of intolerance to haploinsufficiency. The haploinsufficiency profile involved the thalamus, anterior cingulate cortex, and somatomotor network and was correlated with lower general intelligence and higher autism severity scores in 3 unselected and disease cohorts. An exploratory factor analysis confirmed the contribution of these regions to three latent components shared across CNVs and NPs. Our results open new avenues for understanding polygenicity in psychiatric conditions, and the pleiotropic effect of CNVs on cognition and on risk for neuropsychiatric disorders.
Li-Yun y 謝禮雲. "Comparison of intake and plasma levels of vitamin A and carotenoids in COPD patients and healthy people: the association with diet pattern". Thesis, 2009. http://ndltd.ncl.edu.tw/handle/59723055669923476592.
Texto completo中山醫學大學
營養學研究所
97
Oxidative stress is thought to play a key role in the pathogenesis of COPD. Increasing evidence suggested that individuals with a high intake of antioxidative nutrients, such as vitamins C, E, A, and carotenoids tend to maintain better lung function. However, little has been known about the intakes status of these nutrients in COPD patients in Taiwan. Therefore, this case-controlled study elucidated the differences in plasma and intake levels of vitamin A and various carotenoids as well as the association of the plasma concentration of these nutrients and endogenous and H2O2-induced white blood cells (WBC) DNA damage. In addition, we investigated whether the dietary habits of avoiding “cooling” vegetables and fruits affect the intake of these nutrients. Thirty-two COPD patients, who satisfied the criteria with forced expiratory volume in 1 second (FEV1) % predicted less than 80% and a ratio of FEV1 to forced vital capacity (FVC) less than 0.7, were recruited in this study; whereas, forty-three healthy people, who were ≧ 50 years old and with normal lung function, were recruited as control group. We compared the dietary habits and nutrient intakes using a food frequency questionnaire and a 24-h food recall. Blood samples were collected to measure the level of vitamin A, α-carotene, β-carotene, lutein and lycopene. The results showed that the mean intakes of vitamin A, individual carotenoid except for α-carotene or total carotenoids in COPD patients were significantly lower than those of healthy people. On the other hand, the mean plasma concentrations of vitamin A, individual carotenoid except for lutein and lycopene, or total carotenoids were also significantly lower in COPD patients than those of healthy individuals. Furthermore, we investigated the associations between these nutrients with DNA damage in white blood cells (WBC), because the previous study in our lab showed that the endogenous and H2O2-induced WBC DNA damage of COPD patients were significantly higher than those of healthy people. Pooling the data of the two groups showed that total carotenoids concentration was significantly inversely correlated with the H2O2-induced WBC DNA damage (β= -5.343, p=0.043).However, after adjusted for confounders, the inverse association was not statistically significant. In addition, the sum vegetable and fruit intakes frequency of COPD patients was significantly lower than that of healthy people, especially in cooling items. In both COPD and healthy groups, the total consumption of vegetables and fruits was significantly positively associated with the intake of dietary vitamin A,β-carotene, lutein, and total carotenoids; whereas the consumption of cooling items were positively associated, with a borderline significance, with the intake of vitamin A in both groups after adjustment for confounders. After adjusting for confounders, the total consumption vegetables and fruits, rather than each individual nutrient, reduced the OR for COPD. In summary, COPD patients in Taiwan have lower levels of plasma and of intake of vitamin A and several carotenoids than healthy people. The consumption of cooling foods was positively associated with the total consumption of vegetables and fruits which affect the intake of several antioxidative nutrients.
Yi-ChingHuang y 黃怡菁. "The Association between Inhaled Corticosteroid Use and Risk of Mental Disorders among Patients with Asthma-COPD Overlap Syndrome: A Nationwide Population-based Cohort Study". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/zuuq72.
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