Genetic comorbidities in Parkinson's disease

Autor: Nalls, Mike A, Saad, Mohamad, Morris, Huw R, Mudanohwo, Ese, O'Sullivan, Sean S, Pearson, Justin, Perlmutter, Joel S, Pétursson, Hjörvar, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Williams, Nigel, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Sidransky, Ellen, Gasser, Thomas, Smith, Colin, Spencer, Chris C A, Stefánsson, Hreinn, Steinberg, Stacy, Stockton, Joanna D, Strange, Amy, Talbot, Kevin, Tanner, Carlie M, Tashakkori-Ghanbaria, Avazeh, Tison, François, Heutink, Peter, Trabzuni, Daniah, Traynor, Bryan J, Uitterlinden, André G, Velseboer, Daan, Vidailhet, Marie, Walker, Robert, van de Warrenburg, Bart, Wickremaratchi, Mirdhu, Williams-Gray, Caroline H, Wood, Nick, Winder-Rhodes, Sophie, Stefánsson, Kári, Martinez, Maria, Hardy, John, Brice, Alexis, Singleton, Andrew B, Wood, Nicholas W, Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, N. A., Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard, Su, Zhan, Vukcevic, Damjan, Consortium, International Parkinson's Disease Genomics, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, 2, Wellcome Trust Case Control Consortium, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Noyce, Alastair J, Consortium, North American Brain Expression, McCarthy, Mark I, Cookson, Mark R, Consortium, United Kingdom Brain Expression, Gibbs, J Raphael, Hernandez, Dena G, Dillman, Allissa, Nalls, Michael A, Zonderman, Alan B, Arepalli, Sampath, Ferrucci, Luigi, Johnson, Robert, Longo, Dan L, O'Brien, Richard, Nalls, Mike, Traynor, Bryan, Troncoso, Juan, van der Brug, Marcel, Zielke, Ronald H, Weale, Michael E, Ramasamy, Adaikalavan, Plagnol, Vincent, Walker, Rober, Sharma, Manu, Sheerin, Una-Marie, Simón-Sánchez, Javier, Schulte, Claudia, Keller, Margaux F, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Barker, Roger, Ben-Shlomo, Yoav, Berendse, Henk W, Berg, Daniela, Bhatia, Kailash, de Bie, Rob M A, Biffi, Alessandro, Schrag, Anette, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M, Brockmann, Kathrin, Brooks, Janet, Burn, David J, Charlesworth, Gavin, Chen, Honglei, Chinnery, Patrick F, Bestwick, Jonathan P, Chong, Sean, Clarke, Carl E, Cooper, J Mark, Corvol, Jean Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean-François, Deuschl, Günther, Dexter, David T, van Dijk, Karin D, Durif, Frank, Dürr, Alexandra, Evans, Jonathan R, Foltynie, Thomas, Gao, Jianjun, Gardner, Michelle, Goate, Alison, Guerreiro, Rita, Gústafsson, Ómar, Harris, Clare, van Hilten, Jacobus J, Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Huber, Heiko, Hudson, Gavin, Huttenlocher, Johanna, Illig, Thomas, Jónsson, Pálmi V, Lambert, Jean-Charles, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morrison, Karen E
Přispěvatelé: ANS - Amsterdam Neuroscience, Neurology, Graduate School, Erasmus MC other
Rok vydání: 2014
Předmět:
genetics [Crohn Disease]
epidemiology [Schizophrenia]
Single-nucleotide polymorphism
Genome-wide association study
Disease
Comorbidity
Biology
Bioinformatics
Inflammatory bowel disease
Polymorphism
Single Nucleotide

Crohn Disease
genetics [Parkinson Disease]
Risk Factors
ddc:570
Mendelian randomization
mental disorders
Genetics
medicine
Humans
Genetic Predisposition to Disease
genetics [Schizophrenia]
Molecular Biology
GeneralLiterature_REFERENCE(e.g.
dictionaries
encyclopedias
glossaries)

Genetics (clinical)
Genetic association
epidemiology [Crohn Disease]
Association Studies Articles
Parkinson Disease
General Medicine
DNA Methylation
medicine.disease
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
3. Good health
Schizophrenia
CpG Islands
epidemiology [Parkinson Disease]
Genome-Wide Association Study
Zdroj: Human Molecular Genetics, 23, 3, pp. 831-41
Human Molecular Genetics, 23, 831-41
Human molecular genetics, 23(3), 831-841. Oxford University Press
Human Molecular Genetics, 23(3), 831-841
Human molecular genetics 23(3), 831-841 (2013). doi:10.1093/hmg/ddt465
Human Molecular Genetics, 23(3), 831-841. Oxford University Press
ISSN: 0964-6906
DOI: 10.1093/hmg/ddt465
Popis: Parkinson's disease (PD) has a number of known genetic risk factors. Clinical and epidemiological studies have suggested the existence of intermediate factors that may be associated with additional risk of PD. We construct genetic risk profiles for additional epidemiological and clinical factors using known genome-wide association studies (GWAS) loci related to these specific phenotypes to estimate genetic comorbidity in a systematic review. We identify genetic risk profiles based on GWAS variants associated with schizophrenia and Crohn's disease as significantly associated with risk of PD. Conditional analyses adjusting for SNPs near loci associated with PD and schizophrenia or PD and Crohn's disease suggest that spatially overlapping loci associated with schizophrenia and PD account for most of the shared comorbidity, while variation outside of known proximal loci shared by PD and Crohn's disease accounts for their shared genetic comorbidity. We examine brain methylation and expression signatures proximal to schizophrenia and Crohn's disease loci to infer functional changes in the brain associated with the variants contributing to genetic comorbidity. We compare our results with a systematic review of epidemiological literature, while the findings are dissimilar to a degree; marginal genetic associations corroborate the directionality of associations across genetic and epidemiological data. We show a strong genetically defined level of comorbidity between PD and Crohn's disease as well as between PD and schizophrenia, with likely functional consequences of associated variants occurring in brain.
Databáze: OpenAIRE