Unicentre CH-1015 Lausanne http://serval.unil.ch Year : 2010 Computational analysis of the genetic and environmental contributions to disease-related human phenotypes: From predicting adverse lipid response of HIV patients receiving antiretroviral therapy to genome-wide association studies of cardiovascular and lipid related disorders Diana MAREK Diana MAREK, 2010, Computational analysis of the genetic and environmental contributions to disease-related human phenotypes: From predicting adverse lipid response of HIV patients receiving antiretroviral therapy to genome-wide association studies of cardiovascular and lipid related disorders Originally published at : Thesis, University of Lausanne Posted at the University of Lausanne Open Archive. http://serval.unil.ch Droits d’auteur L'Université de Lausanne attire expressément l'attention des utilisateurs sur le fait que tous les documents publiés dans l'Archive SERVAL sont protégés par le droit d'auteur, conformément à la loi fédérale sur le droit d'auteur et les droits voisins (LDA). 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Département de Génétique Médicale - Computational Biology Group Computational analysis of the genetic and environmental contributions to disease-related human phenotypes: From predicting adverse lipid response of HIV patients receiving antiretroviral therapy to genome-wide association studies of cardiovascular and lipid-related disorders Thèse de doctorat ès sciences de la vie (PhD) Présentée à la Faculté de biologie et médecine de l'Université de Lausanne par DIANA MAREK Diplômée de l'Université Paris XI – Orsay (France) Master de Bioinformatique et Biostatistiques Jury Prof. Jérôme Biollaz, Président Prof. Sven Bergmann, Directeur de thèse Prof. Jacques Beckmann, co-Directeur de thèse Prof. Murielle Bochud, Expert Prof. Eckart Zitzler, Expert Lausanne, 2010 Ici et ailleurs, A mes parents, A tous ceux et celles qui ont marqué ma vie, De quelque manière qui soit. Acknowledgements I spent five years in the Department of Medical Genetics at the University of Lausanne for my PhD. Since 2005, I met many people at work and in my life in Lausanne. They all participated in different ways to a very special step in my scientific career and life as a human being. I would like to start with the Department of Medical Genetics (DGM). I saw the DGM growing. I appreciated being one of the first DGM member and the first student of the Computational Biology Group (CBG) founded by Professor Sven Bergmann. I would like to thank the Swiss Institute of Bioinformatics (SIB). The CBG is affiliated to the SIB. It allowed me to meet other scientists from the community, to attend conferences, and especially through the SIB Doctoral School program that I joined to meet other PhD students, and share my experience with them. It has been a fantastic way of knowing what other bioinformaticians are doing in Switzerland and abroad. Thanks to all of you! Through my PhD, I established collaborations with different research groups. I want here to thank them for giving me the opportunity to work with them. First, thanks to Professor Amalio Telenti and Dr Philip Tarr who provided me with the Swiss HIV Cohort Study data and for the fruitful exchanges we had. Working on that topic was very stimulating for me. Thanks to the Cohorte of Lausanne (CoLaus) Study, especially Vincent Mooser (from GSK), Peter Vollenweider and Gérard Waeber (from the CHUV) for setting up such a rich study that allowed me to be part of important large-scale projects which brought together lots of scientists, clinicians and researchers from all around the world. I learnt a lot and I developed my sense of collaboration and teamwork within two big consortia. Thanks to the different members of GIANT and MAGIC. It was very pleasant and rewarding working and exchanging with you. Thanks to the Hypergenes project led by Dr. Carlo Rivolta. I have been involved in the primary steps of this study, which was a different and profitable experience for me. I would also like to thank Dr. Ronan Roussel for the nice collaboration that we established together. In the following section, I want to thank my experts: Prof. Eckart Zitzler and Prof. Murielle Bochud. Writing a thesis takes time but reading all those pages also demands time. Thanks to both of you for accepting to be my experts and for your involvement. Your suggestions, comments and questions have been very much appreciated. During my PhD, my work in the CBG has been supervised by Prof. Sven Bergmann and Prof. Jacques Beckmann. I would like to thank Sven for his patience, advices, open-mindness and support in the good and bad moments of my PhD. I could easily share with you my fears and frustrations regarding my work. It was our first experience as PhD student and supervisor, so we certainly made mistakes but we learnt a lot from each other. I enjoyed working at the CBG with you and the rest of the group. I also want to say a few words about Jacqui. He was always available when needed for scientific and non-scientific matters. I always felt very comfortable talking to you; you pushed me over my limits because you believed I could do it. Both Sven and Jacqui boosted my self-confidence and challenged me to go forward when I wanted to give up. Thanks to the two of you for your encouragement. It helped me a lot all along the way! I have been extremely lucky to be surrounded at work by very smart and nice people. I want to thank here all my colleagues at the CBG for their help and the time they spent with me for questions and discussions. Especially thanks to Zoltán, Bastian, Aitana, Micha, Armand, and Karen. Working with you guys was really great! Aitana, sharing our frustrations and good moments together at work made me realize you are a very special person to me. I also want to thank the whole DGM for all the moments shared together, all the enthusiasm people showed in the department. I had lot of fun working in such a nice environment. I also thank Suzanne, our secretary. She has always been available for any administrative issue, I really appreciated your help. I met lots of people during my PhD time and some of them became good friends. Here I am grateful to them and to my long-time friends. I tried my best not to forget anybody but I am sure that I will. So please, forgive me in advance! Merci à mes amis de plus ou moins longues dates, à ceux que j'ai connus aux différentes époques de la vie, comme Marion et Fred à l'école primaire et en fac. Merci aux étudiants de la filière de Bionfo et Biostats de la fac d'Orsay. Ce furent 3 années géniales. Merci Christophe, merci de m'avoir soutenue durant ces années, que ce soit pour les cours, les TPs, les examens, les coups durs de la vie. Tu as toujours été là, pour m'écouter, rigoler, bosser, et pour m'encourager ! Merci Pierrot pour tous les moments, conversations diverses et variées, partagés au long de nos thèses. Cela m'a permis de continuer le dur cheminement du doctorat. Merci à toi Julien, avec qui j'ai repris contact ces dernières années, nos échanges et nos rencontres autour d'un café sont toujours géniales. Merci à toi Jean, je t'ai connu vers le début de la fin de ma thèse, certainement au moment le plus dur. Tu m'as beaucoup apporté, ton franc-parler, nos convers', nos rigolades et ta façon bien propre à toi de me soutenir m'ont beaucoup aidée. Merci au volley-ball, à ce sport qui est une passion pour moi depuis déjà 16 ans. Il m'a permis de me défouler lorsque j'en avais besoin. Il m'a permis de me vider la tête lorsque je pensais ne plus pouvoir y arriver. Merci à Manon avec qui je prends toujours autant de plaisir à jouer à ce sport. Merci à Sandrine, Gérald, Célia et Sacha, mes Suisses "préférés". Partager le volley, faire les cours de soutien, de bonnes bouffes et des sorties avec vous m'ont fait découvrir une super famille. Je vous ai adoptés comme vous m'avez adoptée. Je suis ravie d'avoir croisé votre chemin et j'en garde d'excellents souvenirs. Merci à Stelle, Marie-Aude, François, Pierre D, Julie, Séverine, Aurélie pour votre bonne humeur, votre écoute, vos encouragements à différents moments de ma thèse. Gracias a vos Marcos, por haberme soportado todos estos años, y haber compartido conmigo momentos de mi vida más o menos fáciles y siempre haberme dado ánimo. Thanks to Arne and David for your encouragement when I was deeply thinking whether I should start a PhD.