Citations 3
Unique genetic architecture of CSF and brain metabolites pinpoints the novel targets for the traits of human wellness
Wang, Ciyang , Western, Daniel , Yang, Chengran , Wang, Lihua , Gorijala, Priyanka , Ruiz, Agustı́n , Pástor, Pau , Fernández, María Victoria , Deming, Yuetiva, Mori, Hiroshi , Perrin, Richard J. , Sung, Yun Ju , Network, Dominantly Inherited Alzheimer, Initiative, Alzheimer’s Disease Neuroimaging, Western, Dan , Ruiz, Agustín , Pastor, Pau , Fernandez, Maria , Panyard, Daniel , Deming, Yuetiva , Boada, Merce , García-González, Pablo , Perrin, Richard , Cruchaga, Carlos , Ali, Muhammad , Timsina, Jigyasha , Engelman, Corinne D. , Boada, Merçé , Cano, Amanda C. , García‐González, Pablo , Graff, Caroline , Lee, Jae‐Hong
No container title available | June 9, 2023 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Brain metabolism perturbation can contribute to traits and diseases. We conducted the first large-scale CSF and brain genome-wide association studies, which identified 219 independent associations (59.8% novel) for 144 CSF metabolites and 36 independent associations (55.6% novel) for 34 brain metabolites. Most of the novel signals (97.7% and 70.0% in CSF and brain) were tissue specific. We also integrated MWAS-FUSION approaches with Mendelian Randomization and colocalization to identify causal metabolites for 27 brain and human wellness phenotypes and identified eight metabolites to be causal for eight traits (11 relationships). Low mannose level was causal to bipolar disorder and as dietary supplement it may provide therapeutic benefits. Low galactosylglycerol level was found causal to Parkinson’s Disease (PD). Our study expanded the knowledge of MQTL in central nervous system, provided insights into human wellness, and successfully demonstrates the utility of combined statistical approaches to inform interventions.
A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers
Zhang, Ming , Ferrari, Raffaele, Tartaglia, Maria Carmela , Keith, Julia , Surace, Ezequiel , Wolf, Uri, Sato, Christine , Grinberg, Mark, Liang, Yan , Xi, Zhengrui, Dupont, Kyle, McGoldrick, Philip, Weichert, Anna , McKeever, Paul M. , Schneider, Raphaël , McCorkindale, Michael D, Manzoni, Claudia , Rademakers, Rosa , Graff, Caroline , Parisi, Joseph E., Petersen, Ronald C., Miller, Bruce L. , Rooij, Jeroen van , Pijnenburg, Yolande A.L. , Zee, Julie van der, Broeckhoven, Christine Van , Ber, Isabelle Le , Deerlin, Vivianna Van, Suh, EunRan , Rohrer, Jonathan D. , Mead, Simon , Öijerstedt, Linn , Pickering‐Brown, Stuart , Rollinson, Sara, Rossi, Giacomina , Tagliavini, Fabrizio , Brooks, William S. , Dobson‐Stone, Carol , Halliday, Glenda M. , Hodges, John R. , Piguet, Olivier , Binetti, Giuliano , Benussi, Luisa , Ghidoni, Roberta , Sorbi, Sandro , Bruni, Amalia C. , Galimberti, Daniela , Rainero, Innocenzo , Rubino, Elisa , Lleó, Alberto, Ruiz, Agustı́n , Hernández, Isabel, Pástor, Pau , Díez-Fairén, Mónica , Borroni, Barbara , Pasquier, Florence , Deramecourt, Vincent , Lebouvier, Thibaud , Perneczky, Robert , Diehl‐Schmid, Janine , Huey, Edward D. , Mayeux, Richard , Nalls, Michael A., Hernandez, Dena G., Singleton, Andrew B., Momeni, Parastoo, Zeng, Zhen , Hardy, John , Zinman, Lorne , Nalls, Michael A., Ramasamy, Adaikalavan , Hodges, John R. , Bartley, Lauren, Hernández, Isabel, Boada, Merçé , Padovani, Alessandro , Cairns, Nigel J. , Serpente, María , Scarpini, Elio, Blesa, Rafael , ouml, Maria Landqvist Wald, Nilsson, Karin , Mackenzie, Ian R. , Hsiung, Ging‐Yuek Robin , Attems, Johannes , Pietrini, Pietro , Baborie, Atik, Jaros, Evelyn, Tierney, Michael C, Razquín, Cristina , Ortega‐Cubero, Sara , Alonso, Elena, Alexopoulos, Panagiotis , Kurz, Alexander , Pinessi, Lorenzo , Rogaeva, Ekaterina, Giaccone, Giorgio , Rowe, James B. , Uphill, James, Collinge, John, Danek, Adrian , Deerlin, Vivianna M Van, Grossman, Murray, Trojanowski, John Q. , Leber, Isabelle, Hannequin, Didier , Golfier, Véronique, Vercelletto, Martine, Brice, Alexis , Nacmias, Benedetta, Bagnoli, Silvia , Hjermind, Lena E. , Riemenschneider, Matthias, Mayhaus, Manuel, Ibach, Bernd, Gasparoni, Gilles, Pichler, Sabrina, Fox, Nick C. , Warren, Jason D. , Spillantini, Maria Grazia , Rizzu, Patrizia , Heutink, Peter , Snowden, Julie S. , Richardson, Anna , Maletta, Raffaele , Frangipane, Francesca, Bernardi, Livia , Conidi, Maria Elena, Smirne, Nicoletta , Rademakers, Rosa, Baker, Matt , Petersen, Ronald , Knopman, David, Josephs, Keith A. , Miller, Bruce L., Karydas, Anna M., Rosen, Howard J., Scheltens, Philip , Logroscino, Giancarlo , Capozzo, Rosa , Novelli, Valeria , Franceschi, M. , Postiglione, Alfredo, Milan, Graziella , Sorrentino, Paolo, Kristiansen, Mark, Chiang, Huei-Hsin, Rollin, Adeline, Deramecourt, Vincent, Kapogiannis, Dimitrios , Waldö, Maria Landqvist , Halliday, Glenda , Logroscino, Giancarlo , Rowe, James B , Hsiung, Gink-Yuek , Miller, Bruce L , Hardy, John , Scheltens, Philip , Rohrer, Jonathan D , Fox, Nick C , Padovani, Alessandro , Ruiz, Agustín , Pastor, Pau , Boada, Merce , Tartaglia, Maria Carmela , Pasquier, Florence , Brooks, William , McGoldrick, Philip , McCorkindale, Michael , Dickson, Dennis W. , Boeve, Bradley F. , Seeley, William W. , Swieten, John C. van , Zee, Julie van der , Deerlin, Vivianna M. Van , Nacmias, Benedetta , Scarpini, Elio , Clarimón, Jordi , Lleó, Alberto , Grafman, Jordan Henry , Robertson, Janice , Rogaeva, Ekaterina A. , Kwok, John B. , Schofield, Peter R. , Thompson, Elizabeth A. , Cruchaga, Carlos , Forloni, Gianluigi , Albani, Diego , Fenoglio, Chiara , Nilsson, Christer, Mann, David , Morris, Christopher M. , Griffiths, Timothy David , McKeith, Ian G. , Thomas, Alan , Wassermann, Eric M. , Tierney, Michael C, George‐Hyslop, Peter St , Schlachetzki, Johannes C. M. , Cappa, Stefano F. , Piaceri, Irene , Nielsen, Jørgen Erik , Riemenschneider, Markus J. , Gu, Wei , Rossor, Martin N. , Morris, Huw R. , Gerhard, Alexander , Cupidi, Chiara , Anfossi, Maria , Gallo, Maura , Dopper, Elise G.P. , Seelaar, Harro , Puca, Annibale Alessandro , Franceschi, Massimo, Chiang, Huei‐Hsin, Ferrucci, Luigi , Brice, Alexis , Rainero, Innocenzo , Galimberti, Daniela , Pijnenburg, Yolande A L , Lebouvier, Thibaud , Graff, Caroline , Borroni, Barbara
Brain | August 31, 2018 | Volume: 141 | Issue: 10 | Pages: 2895-2907
Convergent genetic and expression data implicate immunity in Alzheimer's disease
Jones, Lesley , Lambert, Jean‐Charles , Choi, Seung‐Hoan, Harold, Denise , Vedernikov, Alexey , Escott‐Price, Valentina , Stone, Timothy, Richards, Alexander , Bellenguez, Céline , Sims, Rebecca , DeStefano, Anita L. , Bis, Joshua C. , Beecham, Gary W. , Grenier‐Boley, Benjamin , Russo, Giancarlo , Thornton‐Wells, Tricia A., Jones, Nicola, Smith, Albert V. , Thomas, Charlene , Zélénika, Diana, Kamatani, Yoichiro, Lin, Chiao‐Feng , Schmidt, Helena , Kunkle, Brian W. , Dunstan, Melanie , Ruiz, Agustı́n , Bihoreau, Marie‐Thérèse, Reitz, Christiane, Hollingworth, Paul, Hanon, Olivier , Fitzpatrick, Annette L., Buxbaum, Joseph D. , Campion, Dominique , Crane, Paul K. , Guðnason, Vilmundur , Cruchaga, Carlos , Craig, David W. , Amin, Najaf , Jager, Philip L. De , Deramecourt, Vincent , Johnston, Janet, Evans, Denis A., Lovestone, Simon , Letteneur, Luc, Kornhuber, Johanes, Tárraga, Lluís , Eiriksdottir, Gudny, Goate, Alison , Fiévet, Nathalie, Huentelman, Matthew J. , Gill, Michael , Emilsson, Valur , Brown, Kristelle, Kamboh, M. Ilyas , Keller, Lina, Barberger‐Gateau, Pascale, McGuinness, Bernadette , Larson, Eric B., Dufouil, Carole , Todd, Stephen , Wallon, David , Kehoe, Patrick G. , George‐Hyslop, Peter St , Lleὀ, Alberti, Bayer, Anthony, Tsuang, Debby W. , Yu, Lei, Tsolaki, Magda , Bossù, Paola , Spalletta, Gianfranco , Proitsi, Petra, Collinge, John, Sorbi, Sandro , Hardy, John , Naranjo, María Cándida Déniz, Razquín, Cristina , Bosco, Paola , Clarke, Robert , Brayne, Carol , Galimberti, Daniela , CFAS, MRC, Moebus, Susanne , Mecocci, Patrizia , Zompo, Maria Del, Maier, Wolfgang, Hampel, Harald , Pilotto, Alberto, Bullido, María J. , Panza, Francesco , Caffarra, Paolo , Nacmias, Benedetta , Gilbert, John R., Mayhaus, Manuel, Jessen, Frank , Dichgans, Martin , Lannfelt, Lars , Håkonarson, Håkon , Pichler, Sabrina, Carrasquillo, Minerva M., Beekly, Duane, Alavarez, Victoria, Zou, Fanggeng, Younkin, Steven G., Hamilton‐Nelson, Kara L., Mateo, Ignacio, Faber, Kelley M., Jónsson, Pálmi V. , Combarros, Onofre, O‘Donovan, Michael , Cantwell, Laura B., Blacker, Deborah , Mead, Simon , Harris, Tamara B., Fratiglioni, Laura , Bruijn, Renée F.A.G. de, Passmore, Peter , Montine, Thomas J. , Bettens, Karolien, Rotter, Jerome I. , Brice, Alexis , Morgan, Kevin , Foroud, Tatiana, Kukull, Walter A. , Hannequin, Didier , Powell, John , Nalls, Michael A., Ritchie, Karen , Lunetta, Kathryn L. , Kauwe, John S.K., Boerwinkle, Eric , Riemenschneider, Matthias, Boada, Merçé , Hiltunen, Mikko , Martin, Eden R. , Pástor, Pau , Schmidt, Reinhold, Dartigues, Jean‐François, Mayeux, Richard , Tzourio, Christophe , Hofman, Albert , Nöthen, Markus M. , Graff, Caroline , Haines, Jonathan L. , Lathrop, Mark, Pericak‐Vance, Margaret A. , Launer, Lenore J. , Farrer, Lindsay A. , Duijn, Cornelia M. van , Broeckhoven, Christine Van , Ramı́rez, Alfredo , Schellenberg, Gerard D., Seshadri, Sudha , Amouyel, Philippe , Williams, Julie , Holmans, Peter , Bennett, David A. , Proitsi, Petroula , Ballantyne, Christie M. , Denning, Nicola , Wang, Weixin , Ibrahim‐Verbaas, Carla A. , Naj, Adam Christian , Gerrish, Amy , Jun, Gyungah , Chouraki, Vincent Antoine , Ikram, M. Arfan , Vardarajan, Badri Narayan , Kamatani, Yoichiro, Pasquier, Florence , Becker, Tim , Cruchaga, Carlos , Berr, Claudine , López, Oscar L. , Rubinsztein, David Chaim , Sleegers, Kristel , Myers, Amanda , Love, Seth , Rogaeva, Ekaterina A. , Gallacher, John , Clarimón, Jordi , Bayer, Anthony, Proitsi, Petra, Sánchez-García, Florentino , Fox, Nick C. , Mancuso, Michelangelo , CFAS, MRC, Carrasquillo, Minerva M. , Ingelsson, Martin , Valladares, Otto , Coto, Eliécer , Hamilton‐Nelson, Kara L. , Owen, Michael J. , Soininen, Hilkka S. , Mosley, Thomas H. , Bennett, David , Holmes, Clive , Riemenschneider, Matthias, Rujescu, Dan , Psaty, Bruce M. , Bennett, David A. , Dichgans, Martin , Ramirez, Alfredo , Hakonarson, Hakon , Nöthen, Markus M , Seshadri, Sudha , Hardy, John , Amouyel, Philippe , Tzourio, Christophe , van Duijn, Cornelia M , Smith, Albert V , Ballantyne, Christie M , Rotter, Jerome I , Moebus, Susanne , Ruiz, Agustín , Pastor, Pau , Boada, Merce , Tsolaki, Magda , Brice, Alexis , Goate, Alison M , Galimberti, Daniela , Escott-Price, Valentina , Mecocci, Patrizia , Nacmias, Benedetta , Graff, Caroline , Riemenschneider, Markus J.
Alzheimer's & Dementia | December 20, 2014 | Volume: 11 | Issue: 6 | Pages: 658-671
AbstractBackgroundLate‐onset Alzheimer's disease (AD) is heritable with 20 genes showing genome‐wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.MethodsThe ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.ResultsALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10−12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10−11), cholesterol transport (P = 2.96 × 10−9), and proteasome‐ubiquitin activity (P = 1.34 × 10−6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002–.05).ConclusionsThe immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.