Ítem
Acceso Abierto

Genetic Epidemiology of Polyautoimmunity and Common Autoimmunity in Colombia — Proof of Principle

Mostrar el registro sencillo de la publicación
dc.contributor.advisorAnaya, Juan-Manuel
dc.creatorCastiblanco Quinche, John
dc.creator.degreeDoctor en Ciencias Biomédicas
dc.date.accessioned2017-09-03T19:14:28Z
dc.date.available2017-09-03T19:14:28Z
dc.date.created2016-11-28
dc.date.issued2016
dc.descriptionIntroducción: Las enfermedades autoinmunes (EA) son responsables de una gran porción de discapacidad y morbilidad a nivel mundial. Generalmente, las investigaciones científicas se centran en una sola enfermedad, aunque los fenotipos autoinmunes podrían estar representados por efectos pleiotrópicos en genes no-específicos al presentar mecanismos inmunogenéticos similares. Múltiples casos de una sola enfermedad dentro de familia son evidentes, y aún más sorprendente son los individuos en aquellas familias que sufren de múltiples enfermedades autoinmunes. Este estudio exploró la dinámica de agregación familiar y la segregación en pacientes con EA, poliautoimmunidad (polyA) (presentar por lo menos dos AD) y el síndrome autoinmune múltiple (MAS) (presentar tres o más EA). Por otra parte, se examinó el efecto y la importancia de la homocigosis y la ancestría en individuos afectados colombianos con respecto a desarrollar una EA. Métodos: La agregación y segregación familiar se examinó en familiares de primer grado para un rasgo binario en 210 familias afectadas por EA. La homocigosis se estudió en dos enfoques: (I) Comparación de casos y controles mediante la evaluación del efecto de la homocigosis al nivel de todo el genoma en 453 individuos no relacionados (121 EA tardía, 79 EA temprana, 40 polyA, 30 MAS y 183 individuos control); (II) por un estudio de ligamiento no-paramétrico en parientes afectados en 35 familias con MAS, 49 con polyA, 104 con EA tardía, y 83 con EA temprana. La ancestría se examinó en todos los individuos afectados y sanos colombianos, así como individuos originados a partir de poblaciones de referencia, suponiendo tres grupos ancestrales (k = 3) (i.e., europea, amerindia y africana). El efecto de ancestría para los rasgos estudiados se comparó y analizó mediante regresión logística con respecto a los controles. Todos los individuos y las familias fueron tratados e invitados a participar en el Centro de Investigación de Enfermedades Autoinmunes (CREA) en Medellín y Bogotá, Colombia. Resultados: Este proyecto sugiere que las EA no son rasgos independientes y que el género, la edad y la edad de inicio representan factores que definen y permiten el estudio de la dinámica de los rasgos dentro del grupo familiar. Más allá, los datos de segregación proporcionaron soporte para el papel del componente genético en la etiología de las EAs en las familias de aparición tardía, mientras que para las familias de inicio temprano no se observó un papel claro, tal vez debido a la edad relativamente joven familiar. Los datos también mostraron diferencias en la homocigosidad en relación con los controles para las personas de aparición temprana, mientras que en la inspección de varios marcadores locales se sugiere que la homocigosis se encuentra asociada con la protección/susceptibilidad para la EA temprana, de inicio tardío, polyA y MAS. Por otra parte, la ancestría y la autoinmunidad en muestras de colombianos mostraron cómo el paisaje rasgo autoinmune no es un escenario blanco y negro, sino más bien una colorida mezcla de factores genéticos y ambientales. Todos los marcadores analizados fueron muy informativos con una baja frecuencia del alelo nulo haciéndolos óptimos y fiables para estudios de diversidad genética. Conclusiones: Este estudio asumió a la autoinmunidad como un rasgo más que un fenotipo clínico y como un rasgo continuo que presenta fenotipos extremos. Los datos sugieren que las EAs no son independientes. Por último, una EA individual, definida por síntomas y signos, podría no ser completamente yuxtapuesta con una EA definida por el medio ambiente y genética, lo que hace aún más difícil la tarea de definir y dilucidar los mecanismos de las enfermedades.spa
dc.description.abstractBackground: Autoimmune diseases (AD) are responsible for a substantial amount of disability and morbidity worldwide. Research generally focuses on a single disease, although autoimmune phenotypes could represent pleiotropic outcomes of non-specific disease genes underlying similar immunogenetic mechanisms. While it is apparent that multiple cases of a single disease cluster within families, more striking are the individuals in those families afflicted with multiple autoimmune diseases. This study explored the dynamics of familial aggregation and segregation in AD (i.e., having at least one AD), polyautoimmunity (polyA) (i.e., having at least two ADs) and multiple autoimmune syndrome (MAS) (i.e., having three or more ADs) patients. Moreover, this project examined the effect and importance of homozygosity and whether the ancestry component of Colombian affected individuals is associated with susceptibility/protection to develop an AD. Methods: Familial aggregation was examined for first-degree relatives. Segregation analysis for a binary trait was implemented on 210 single ascertained multiplex AD families. Homozygosity was examined by two approaches: (I) a case – control comparison and evaluation on the effect of homozygosity at the genome-wide level, including 453 genotyped unrelated individuals (121 late-onset AD, 79 early-onset, 40 polyA, 30 MAS and 183 healthy control individuals); and (II) a model-free affected pair linkage approach which included 35 MAS, 49 polyA, 104 late-, and 83 early-onset multiplex families. The admixture effect was examined in all included Colombian affected and healthy individuals, as well as in the individuals originated from reference populations, assuming three ancestral groups (k=3) (i.e., European, Amerindian and African). The ancestry component effect for the studied traits was compared and examined by logistic regression relative to controls. All individuals and families were treated and recruited at the Center for Autoimmune Diseases Research (CREA) from Medellin and Bogota, Colombia, South America. Results: This project provided data supporting that polyA and MAS are not AD independent traits and that gender, age and age of onset represent factors that define and allow the study of the dynamics of the traits within the familial group. Also, segregation data provided evidence for the genetic component role in the etiology of AD in late-onset families, while for early-onset families and perhaps because of their the relatively familial young status, eluded a clear picture of autoimmunity segregation and aggregation. The data also showed homozygosity differences relative to controls for early-onset individuals, while on local inspection several markers suggested homozygosity associated with protection/susceptibility to early-, late-onset, polyA and/or MAS. Moreover, ancestry and autoimmunity in Colombian samples showed how the autoimmune trait landscape is not a black and white scenario but rather a colorful mix of genetic and environmental factors. All markers analyzed were highly informative with a low null allele frequency making them optimal and reliable for genetic diversity studies. Conclusions: This study presumed autoimmunity as a trait rather than a clinical phenotype and tried to approach AD as a continuous trait presenting extreme phenotypes. Data suggested that AD are not independent traits and that gender, age and age of onset represent factors play a role and allow to study of the dynamic of the traits. Finally, a clinical defined individual AD, defined by symptoms and signs, might not be completely juxtaposed to the AD trait defined by environment and genetics, which makes even more difficult the task to define and untangle disease mechanisms.eng
dc.description.sponsorshipCenter for Autoimmune Disease Research (CREA)spa
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.48713/10336_13733
dc.identifier.urihttp://repository.urosario.edu.co/handle/10336/13733
dc.language.isospa
dc.publisherUniversidad del Rosariospa
dc.publisher.departmentFacultad de Ciencias Naturales y Matemáticasspa
dc.publisher.programDoctorado en Ciencias Biomédicasspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto completo)spa
dc.rights.ccAtribución-NoComercial-SinDerivadas 2.5 Colombiaspa
dc.rights.licenciaEL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma. PARGRAFO: En caso de presentarse cualquier reclamación o acción por parte de un tercero en cuanto a los derechos de autor sobre la obra en cuestión, EL AUTOR, asumirá toda la responsabilidad, y saldrá en defensa de los derechos aquí autorizados; para todos los efectos la universidad actúa como un tercero de buena fe. EL AUTOR, autoriza a LA UNIVERSIDAD DEL ROSARIO, para que en los términos establecidos en la Ley 23 de 1982, Ley 44 de 1993, Decisión andina 351 de 1993, Decreto 460 de 1995 y demás normas generales sobre la materia, utilice y use la obra objeto de la presente autorización. -------------------------------------- POLITICA DE TRATAMIENTO DE DATOS PERSONALES. Declaro que autorizo previa y de forma informada el tratamiento de mis datos personales por parte de LA UNIVERSIDAD DEL ROSARIO para fines académicos y en aplicación de convenios con terceros o servicios conexos con actividades propias de la academia, con estricto cumplimiento de los principios de ley. Para el correcto ejercicio de mi derecho de habeas data cuento con la cuenta de correo habeasdata@urosario.edu.co, donde previa identificación podré solicitar la consulta, corrección y supresión de mis datos.spa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.5/co/
dc.source.bibliographicCitationJacobson DL, Gange SJ, Rose NR, Graham NM. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clinical immunology and immunopathology. 1997;84(3):223-43
dc.source.bibliographicCitationMariani SM. Genes and autoimmune diseases - a complex inheritance. MedGenMed. 2004;6(4):18.
dc.source.bibliographicCitationVyse TJ, Todd JA. Genetic analysis of autoimmune disease. Cell. 1996;85(3):311-8.
dc.source.bibliographicCitationAnaya JM, Corena R, Castiblanco J, Rojas-Villarraga A, Shoenfeld Y. The kaleidoscope of autoimmunity: multiple autoimmune syndromes and familial autoimmunity. Expert Review of Clinical Immunology. 2007;3(4):623-35.
dc.source.bibliographicCitationAnaya JM, Gomez L, Castiblanco J. Is there a common genetic basis for autoimmune diseases? Clinical & developmental immunology. 2006;13(2-4):185-95.
dc.source.bibliographicCitationCotsapas C, Hafler DA. Immune-mediated disease genetics: the shared basis of pathogenesis. Trends in immunology. 2013;34(1):22-6.
dc.source.bibliographicCitationCardenas-Roldan J, Rojas-Villarraga A, Anaya JM. How do autoimmune diseases cluster in families? A systematic review and meta-analysis. BMC medicine. 2013;11:73.
dc.source.bibliographicCitationBaranzini SE. The genetics of autoimmune diseases: a networked perspective. Current opinion in immunology. 2009;21(6):596-605.
dc.source.bibliographicCitationZhernakova A, van Diemen CC, Wijmenga C. Detecting shared pathogenesis from the shared genetics of immune-related diseases. Nature reviews Genetics. 2009;10(1):43-55.
dc.source.bibliographicCitationBias WB, Reveille JD, Beaty TH, Meyers DA, Arnett FC. Evidence that autoimmunity in man is a Mendelian dominant trait. American journal of human genetics. 1986;39(5):584-602.
dc.source.bibliographicCitationWandstrat A, Wakeland E. The genetics of complex autoimmune diseases: non-MHC susceptibility genes. Nat Immunol. 2001;2(9):802-9.
dc.source.bibliographicCitationInvernizzi P. Future directions in genetic for autoimmune diseases. J Autoimmun. 2009;33(1):1-2.
dc.source.bibliographicCitationAnaya JM, Tobon GJ, Vega P, Castiblanco J. Autoimmune disease aggregation in families with primary Sjogren's syndrome. J Rheumatol. 2006;33(11):2227-34.
dc.source.bibliographicCitationTobon GJ, Arango A, Abad V, Garcia J, Cuervo H, Velasquez A, et al. Clinical and immunological characteristics of type 1 diabetes mellitus in a northwestern Colombian population. Diabetes Res Clin Pract. 2006;72(2):170-5.
dc.source.bibliographicCitationSloka S. Observations on recent studies showing increased co-occurrence of autoimmune diseases. J Autoimmun. 2002;18(3):251-7.
dc.source.bibliographicCitationBlank M, Gershwin ME. Autoimmunity: from the mosaic to the kaleidoscope. J Autoimmun. 2008;30(1-2):1-4.
dc.source.bibliographicCitationRojas-Villarraga A, Amaya-Amaya J, Rodriguez-Rodriguez A, Mantilla RD, Anaya JM. Introducing polyautoimmunity: secondary autoimmune diseases no longer exist. Autoimmune diseases. 2012;2012:254319.
dc.source.bibliographicCitationAnaya JM, Castiblanco J, Rojas-Villarraga A, Pineda-Tamayo R, Levy RA, Gomez-Puerta J, et al. The Multiple Autoimmune Syndromes. A Clue for the Autoimmune Tautology. Clinical reviews in allergy & immunology. 2012.
dc.source.bibliographicCitationAnaya JM, Rojas-Villarraga A, Garcia-Carrasco M. The autoimmune tautology: from polyautoimmunity and familial autoimmunity to the autoimmune genes. Autoimmune diseases. 2012;2012:297193.
dc.source.bibliographicCitationCardenas-Roldan J, Rojas-Villarraga A, Anaya JM. How do autoimmune diseases cluster in families? A systematic review and meta-analysis. BMC medicine. 2013;11(1):73.
dc.source.bibliographicCitationAnaya JM, Castiblanco J, Tobon GJ, Garcia J, Abad V, Cuervo H, et al. Familial clustering of autoimmune diseases in patients with type 1 diabetes mellitus. Journal of autoimmunity. 2006;26(3):208-14.
dc.source.bibliographicCitationHumbert P, Dupond JL. [Multiple autoimmune syndromes]. Ann Med Interne (Paris). 1988;139(3):159-68.
dc.source.bibliographicCitationSchmidt MB. Eine biglandulare Erkrankung (Nebennieren und Schilddrüse) bei Morbus Addisonii. Verh Dtsch Ges Pathol. 1926;21(212-21).
dc.source.bibliographicCitationBetterle C, Lazzarotto F, Presotto F. Autoimmune polyglandular syndrome Type 2: the tip of an iceberg? Clinical and experimental immunology. 2004;137(2):225-33.
dc.source.bibliographicCitationEisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. The New England journal of medicine. 2004;350(20):2068-79.
dc.source.bibliographicCitationAnaya JM, Corena R, Castiblanco J, Rojas-Villarraga A, Shoenfeld Y. The kaleidoscope of autoimmunity: multiple autoimmune syndromes and familial autoimmunity. Expert review of clinical immunology. 2007;3(4):623-35.
dc.source.bibliographicCitationVoight BF, Cotsapas C. Human genetics offers an emerging picture of common pathways and mechanisms in autoimmunity. Current opinion in immunology. 2012;24(5):552-7.
dc.source.bibliographicCitationMori M, Yamada R, Kobayashi K, Kawaida R, Yamamoto K. Ethnic differences in allele frequency of autoimmune-disease-associated SNPs. Journal of human genetics. 2005;50(5):264-6.
dc.source.bibliographicCitationGibson G. Decanalization and the origin of complex disease. Nature reviews Genetics. 2009;10(2):134-40.
dc.source.bibliographicCitationAylsworth AS. Defining disease phenotypes. In: Haines JL, Pericak-Vance MA, editors. Approaches to Gene Mapping in Complex Human Diseases. New York, NY: Wiley-Liss; 1998. p. 53-76.
dc.source.bibliographicCitationRose AM, Bell LC. Epistasis and immunity: the role of genetic interactions in autoimmune diseases. Immunology. 2012;137(2):131-8.
dc.source.bibliographicCitationBurton PR, Tobin MD, Hopper JL. Key concepts in genetic epidemiology. Lancet. 2005;366(9489):941-51.
dc.source.bibliographicCitationGoris A, Liston A. The immunogenetic architecture of autoimmune disease. Cold Spring Harbor perspectives in biology. 2012;4(3).
dc.source.bibliographicCitationBarcellos LF, Kamdar BB, Ramsay PP, DeLoa C, Lincoln RR, Caillier S, et al. Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis: a descriptive study. The Lancet Neurology. 2006;5(11):924-31.
dc.source.bibliographicCitationSomers EC, Thomas SL, Smeeth L, Hall AJ. Autoimmune diseases co-occurring within individuals and within families: a systematic review. Epidemiology. 2006;17(2):202-17.
dc.source.bibliographicCitationMichou L, Rat AC, Lasbleiz S, Bardin T, Cornelis F. Prevalence and distribution of autoimmune diseases in 368 rheumatoid arthritis families. The Journal of rheumatology. 2008;35(5):790-6.
dc.source.bibliographicCitationAlarcon-Segovia D, Alarcon-Riquelme ME, Cardiel MH, Caeiro F, Massardo L, Villa AR, et al. Familial aggregation of systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases in 1,177 lupus patients from the GLADEL cohort. Arthritis and rheumatism. 2005;52(4):1138-47.
dc.source.bibliographicCitationPrahalad S, Shear ES, Thompson SD, Giannini EH, Glass DN. Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis. Arthritis and rheumatism. 2002;46(7):1851-6.
dc.source.bibliographicCitationKumar V, Rajadhyaksha M, Wortsman J. Celiac disease-associated autoimmune endocrinopathies. Clin Diagn Lab Immunol. 2001;8(4):678-85.
dc.source.bibliographicCitationHafler DA. Multiple sclerosis. J Clin Invest. 2004;113(6):788-94.
dc.source.bibliographicCitationAnaya JM, Delgado-Vega AM, Castiblanco J. Genetic basis of Sjogren syndrome. How strong is the evidence? Clinical & developmental immunology. 2006;13(2):209-22.
dc.source.bibliographicCitationHerrick AL, Worthington J. Genetic epidemiology: systemic sclerosis. Arthritis Res. 2002;4(3):165-8.
dc.source.bibliographicCitationJawaheer D, Lum RF, Amos CI, Gregersen PK, Criswell LA. Clustering of disease features within 512 multicase rheumatoid arthritis families. Arthritis and rheumatism. 2004;50(3):736-41.
dc.source.bibliographicCitationChistiakov DA. Immunogenetics of Hashimoto's thyroiditis. J Autoimmune Dis. 2005;2(1):1.
dc.source.bibliographicCitationThanvi BR, Lo TC. Update on myasthenia gravis. Postgrad Med J. 2004;80(950):690-700.
dc.source.bibliographicCitationBarragan-Martinez C, Amaya-Amaya J, Pineda-Tamayo R, Mantilla RD, Castellanos-de la Hoz J, Bernal-Macias S, et al. Gender differences in Latin-American patients with rheumatoid arthritis. Gender medicine. 2012;9(6):490-510 e5.
dc.source.bibliographicCitationFairweather D, Frisancho-Kiss S, Rose NR. Sex differences in autoimmune disease from a pathological perspective. The American journal of pathology. 2008;173(3):600-9.
dc.source.bibliographicCitationRubtsov AV, Rubtsova K, Kappler JW, Marrack P. Genetic and hormonal factors in female-biased autoimmunity. Autoimmunity reviews. 2010;9(7):494-8.
dc.source.bibliographicCitationChitnis S, Monteiro J, Glass D, Apatoff B, Salmon J, Concannon P, et al. The role of X-chromosome inactivation in female predisposition to autoimmunity. Arthritis Res. 2000;2(5):399-406.
dc.source.bibliographicCitationStewart JJ. Theory and treatment of the X-inactivation chimera in female-prevalent autoimmune disease. Arch Immunol Ther Exp (Warsz). 1999;47(6):355-9.
dc.source.bibliographicCitationReveille JD, Wilson RW, Provost TT, Bias WB, Arnett FC. Primary Sjogren's syndrome and other autoimmune diseases in families. Prevalence and immunogenetic studies in six kindreds. Ann Intern Med. 1984;101(6):748-56.
dc.source.bibliographicCitationPriori R, Medda E, Conti F, Cassara EA, Danieli MG, Gerli R, et al. Familial autoimmunity as a risk factor for systemic lupus erythematosus and vice versa: a case-control study. Lupus. 2003;12(10):735-40.
dc.source.bibliographicCitationTait KF, Marshall T, Berman J, Carr-Smith J, Rowe B, Todd JA, et al. Clustering of autoimmune disease in parents of siblings from the Type 1 diabetes Warren repository. Diabet Med. 2004;21(4):358-62.
dc.source.bibliographicCitationCoyle PK. Gender issues. Neurol Clin. 2005;23(1):39-60, v-vi.
dc.source.bibliographicCitationGuo SW, Tuomilehto J. Preferential transmission of type 1 diabetes from parents to offspring: fact or artifact? Genet Epidemiol. 2002;23(4):323-34.
dc.source.bibliographicCitationKantarci OH, Barcellos LF, Atkinson EJ, Ramsay PP, Lincoln R, Achenbach SJ, et al. Men transmit MS more often to their children vs women: the Carter effect. Neurology. 2006;67(2):305-10.
dc.source.bibliographicCitationCarter CO. The inheritance of congenital pyloric stenosis. Br Med Bull. 1961;17:251-4.
dc.source.bibliographicCitationAnaya JM, Shoenfeld Y, Correa PA, Garcia-Carrasco M, Cervera R. Autoimmunity and Autoimmune Disease. 1 ed. Anaya JM, editor. Medellin: CIB; 2005.
dc.source.bibliographicCitationArcos-Burgos M, Parodi E, Salgar M, Bedoya E, Builes J, Jaramillo D, et al. Vitiligo: complex segregation and linkage disequilibrium analyses with respect to microsatellite loci spanning the HLA. Hum Genet. 2002;110(4):334-42.
dc.source.bibliographicCitationLin JP, Cash JM, Doyle SZ, Peden S, Kanik K, Amos CI, et al. Familial clustering of rheumatoid arthritis with other autoimmune diseases. Human genetics. 1998;103(4):475-82.
dc.source.bibliographicCitationAlamanos Y, Tsifetaki N, Voulgari PV, Venetsanopoulou AI, Siozos C, Drosos AA. Epidemiology of primary Sjogren's syndrome in north-west Greece, 1982-2003. Rheumatology. 2006;45(2):187-91.
dc.source.bibliographicCitationJacobsson LT, Hanson RL, Knowler WC, Pillemer S, Pettitt DJ, McCance DR, et al. Decreasing incidence and prevalence of rheumatoid arthritis in Pima Indians over a twenty-five-year period. Arthritis and rheumatism. 1994;37(8):1158-65.
dc.source.bibliographicCitationGoransson LG, Haldorsen K, Brun JG, Harboe E, Jonsson MV, Skarstein K, et al. The point prevalence of clinically relevant primary Sjogren's syndrome in two Norwegian counties. Scandinavian journal of rheumatology. 2011;40(3):221-4.
dc.source.bibliographicCitationZurauskas J, Beroukas D, Walker JG, Smith MD, Ahern MJ, Roberts-Thomson PJ. Scleroderma in Australian aborigines. Internal medicine journal. 2005;35(1):60-2.
dc.source.bibliographicCitationHelmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis and rheumatism. 2008;58(1):15-25.
dc.source.bibliographicCitationRoden DM. Personalized medicine and the genotype-phenotype dilemma. Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 2011;31(1):17-23.
dc.source.bibliographicCitationMcKinney C, Merriman ME, Chapman PT, Gow PJ, Harrison AA, Highton J, et al. Evidence for an influence of chemokine ligand 3-like 1 (CCL3L1) gene copy number on susceptibility to rheumatoid arthritis. Annals of the rheumatic diseases. 2008;67(3):409-13.
dc.source.bibliographicCitationRai E, Wakeland EK. Genetic predisposition to autoimmunity--what have we learned? Seminars in immunology. 2011;23(2):67-83.
dc.source.bibliographicCitationLettre G, Rioux JD. Autoimmune diseases: insights from genome-wide association studies. Human molecular genetics. 2008;17(R2):R116-21.
dc.source.bibliographicCitationZhernakova A, Stahl EA, Trynka G, Raychaudhuri S, Festen EA, Franke L, et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS genetics. 2011;7(2):e1002004.
dc.source.bibliographicCitationSmyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. The New England journal of medicine. 2008;359(26):2767-77.
dc.source.bibliographicCitationFesten EA, Goyette P, Green T, Boucher G, Beauchamp C, Trynka G, et al. A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn's disease and celiac disease. PLoS genetics. 2011;7(1):e1001283.
dc.source.bibliographicCitationSirota M, Schaub MA, Batzoglou S, Robinson WH, Butte AJ. Autoimmune disease classification by inverse association with SNP alleles. PLoS genetics. 2009;5(12):e1000792.
dc.source.bibliographicCitationStahl EA, Wegmann D, Trynka G, Gutierrez-Achury J, Do R, Voight BF, et al. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nature genetics. 2012;44(5):483-9.
dc.source.bibliographicCitationJohar A, Sarmiento-Monroy JC, Rojas-Villarraga A, Silva-Lara MF, Patel HR, Mantilla RD, et al. Definition of mutations in polyautoimmunity. J Autoimmun. 2016;72:65-72.
dc.source.bibliographicCitationJohar AS, Mastronardi C, Rojas-Villarraga A, Patel HR, Chuah A, Peng K, et al. Novel and rare functional genomic variants in multiple autoimmune syndrome and Sjogren's syndrome. Journal of translational medicine. 2015;13:173.
dc.source.bibliographicCitationWang K, Baldassano R, Zhang H, Qu HQ, Imielinski M, Kugathasan S, et al. Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects. Human molecular genetics. 2010;19(10):2059-67.
dc.source.bibliographicCitationEaton WW, Rose NR, Kalaydjian A, Pedersen MG, Mortensen PB. Epidemiology of autoimmune diseases in Denmark. Journal of autoimmunity. 2007;29(1):1-9.
dc.source.bibliographicCitationAnaya JM, Ramirez-Santana C, Alzate MA, Molano-Gonzalez N, Rojas-Villarraga A. The Autoimmune Ecology. Front Immunol. 2016;7:139.
dc.source.bibliographicCitationAbecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, et al. A map of human genome variation from population-scale sequencing. Nature. 2010;467(7319):1061-73.
dc.source.bibliographicCitationShendure J, Lieberman Aiden E. The expanding scope of DNA sequencing. Nature biotechnology. 2012;30(11):1084-94.
dc.source.bibliographicCitationA user's guide to the encyclopedia of DNA elements (ENCODE). PLoS biology. 2011;9(4):e1001046.
dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subjectAutoinmunidadspa
dc.subjectPoliautoinmunidadspa
dc.subjectSindrome Autoinmune Multiplespa
dc.subjectEnfermedad Autoinmunespa
dc.subjectAutoinmunidad Familialspa
dc.subject.ddcIncidencia & prevención de la enfermedad
dc.subject.decsEpidemiologíaspa
dc.subject.decsEnfermedades autoinmunesspa
dc.subject.decsInmunologíaspa
dc.subject.keywordAutoimmunityeng
dc.subject.keywordPolyautoimmunityeng
dc.subject.keywordMultiple Autoimmune syndromeeng
dc.subject.keywordFamilial Autoimmunityeng
dc.subject.keywordAutoimmune diseaseeng
dc.subject.lembCiencias médicasspa
dc.titleGenetic Epidemiology of Polyautoimmunity and Common Autoimmunity in Colombia — Proof of Principlespa
dc.typedoctoralThesiseng
dc.type.hasVersioninfo:eu-repo/semantics/acceptedVersion
dc.type.spaTesis de doctoradospa
local.department.reportEscuela de Medicina y Ciencias de la Saludspa
Archivos
Bloque original
Mostrando1 - 1 de 1
Miniatura
Nombre:
CastiblancoQuinche-John-2017.pdf
Tamaño:
4.73 MB
Formato:
Adobe Portable Document Format
Descripción:
Documento de tesis completo
Descargar
Colecciones
Doctorado en Ciencias Biomédicas