Browsing by Subject "Alzheimer’s Disease Neuroimaging Initiative"

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    Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer's Disease.
    (Journal of Alzheimer's disease : JAD, 2021-10-13) Liu, Hongliang; Lutz, Michael; Luo, Sheng; Alzheimer’s Disease Neuroimaging Initiative
    Mild cognitive impairment (MCI) is a heterogeneous condition and MCI patients are at increased risk of progression to dementia due to Alzheimer's disease (AD). In this study, we aim to evaluate the associations between polygenic risk scores (PRSs) and 1) time to AD progression from MCI, 2) changes in longitudinal cognitive impairment, and 3) biomarkers from cerebrospinal fluid and imaging. We constructed PRS by using 40 independent non-APOE SNPs from well-replicated AD GWASs and tested its association with the progression time from MCI to AD by using 767 MCI patients from the ADNI study and 1373 patients from the NACC study. PRSs calculated with other methods were also computed. We found that the PRS constructed with SNPs that reached genome-wide significance predicted the progression from MCI to AD (beta = 0.182, se = 0.061, p = 0.003) after adjusting for the demographic and clinical variables. This association was replicated in the NACC dataset (beta = 0.094, se = 0.037, p = 0.009). Further analyses revealed that PRS was associated with the increased ADAS-Cog11/ADAS-Cog13/ADASQ4 scores, tau/ptau levels, and cortical amyloid burdens (PIB and AV45), but decreased hippocampus and entorhinal cortex volumes (p <  0.05). Mediation analysis showed that the effect of PRS on the increased risk of AD may be mediated by Aβ 42 (beta = 0.056, SE = 0.026, p = 0.036). Our findings suggest that PRS can be useful for the prediction of time to AD and other clinical changes after the diagnosis of MCI.
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    The genetic architecture of the human cerebral cortex.
    (Science (New York, N.Y.), 2020-03) Grasby, Katrina L; Jahanshad, Neda; Painter, Jodie N; Colodro-Conde, Lucía; Bralten, Janita; Hibar, Derrek P; Lind, Penelope A; Pizzagalli, Fabrizio; Ching, Christopher RK; McMahon, Mary Agnes B; Shatokhina, Natalia; Zsembik, Leo CP; Thomopoulos, Sophia I; Zhu, Alyssa H; Strike, Lachlan T; Agartz, Ingrid; Alhusaini, Saud; Almeida, Marcio AA; Alnæs, Dag; Amlien, Inge K; Andersson, Micael; Ard, Tyler; Armstrong, Nicola J; Ashley-Koch, Allison; Atkins, Joshua R; Bernard, Manon; Brouwer, Rachel M; Buimer, Elizabeth EL; Bülow, Robin; Bürger, Christian; Cannon, Dara M; Chakravarty, Mallar; Chen, Qiang; Cheung, Joshua W; Couvy-Duchesne, Baptiste; Dale, Anders M; Dalvie, Shareefa; de Araujo, Tânia K; de Zubicaray, Greig I; de Zwarte, Sonja MC; den Braber, Anouk; Doan, Nhat Trung; Dohm, Katharina; Ehrlich, Stefan; Engelbrecht, Hannah-Ruth; Erk, Susanne; Fan, Chun Chieh; Fedko, Iryna O; Foley, Sonya F; Ford, Judith M; Fukunaga, Masaki; Garrett, Melanie E; Ge, Tian; Giddaluru, Sudheer; Goldman, Aaron L; Green, Melissa J; Groenewold, Nynke A; Grotegerd, Dominik; Gurholt, Tiril P; Gutman, Boris A; Hansell, Narelle K; Harris, Mathew A; Harrison, Marc B; Haswell, Courtney C; Hauser, Michael; Herms, Stefan; Heslenfeld, Dirk J; Ho, New Fei; Hoehn, David; Hoffmann, Per; Holleran, Laurena; Hoogman, Martine; Hottenga, Jouke-Jan; Ikeda, Masashi; Janowitz, Deborah; Jansen, Iris E; Jia, Tianye; Jockwitz, Christiane; Kanai, Ryota; Karama, Sherif; Kasperaviciute, Dalia; Kaufmann, Tobias; Kelly, Sinead; Kikuchi, Masataka; Klein, Marieke; Knapp, Michael; Knodt, Annchen R; Krämer, Bernd; Lam, Max; Lancaster, Thomas M; Lee, Phil H; Lett, Tristram A; Lewis, Lindsay B; Lopes-Cendes, Iscia; Luciano, Michelle; Macciardi, Fabio; Marquand, Andre F; Mathias, Samuel R; Melzer, Tracy R; Milaneschi, Yuri; Mirza-Schreiber, Nazanin; Moreira, Jose CV; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Najt, Pablo; Nakahara, Soichiro; Nho, Kwangsik; Olde Loohuis, Loes M; Orfanos, Dimitri Papadopoulos; Pearson, John F; Pitcher, Toni L; Pütz, Benno; Quidé, Yann; Ragothaman, Anjanibhargavi; Rashid, Faisal M; Reay, William R; Redlich, Ronny; Reinbold, Céline S; Repple, Jonathan; Richard, Geneviève; Riedel, Brandalyn C; Risacher, Shannon L; Rocha, Cristiane S; Mota, Nina Roth; Salminen, Lauren; Saremi, Arvin; Saykin, Andrew J; Schlag, Fenja; Schmaal, Lianne; Schofield, Peter R; Secolin, Rodrigo; Shapland, Chin Yang; Shen, Li; Shin, Jean; Shumskaya, Elena; Sønderby, Ida E; Sprooten, Emma; Tansey, Katherine E; Teumer, Alexander; Thalamuthu, Anbupalam; Tordesillas-Gutiérrez, Diana; Turner, Jessica A; Uhlmann, Anne; Vallerga, Costanza Ludovica; van der Meer, Dennis; van Donkelaar, Marjolein MJ; van Eijk, Liza; van Erp, Theo GM; van Haren, Neeltje EM; van Rooij, Daan; van Tol, Marie-José; Veldink, Jan H; Verhoef, Ellen; Walton, Esther; Wang, Mingyuan; Wang, Yunpeng; Wardlaw, Joanna M; Wen, Wei; Westlye, Lars T; Whelan, Christopher D; Witt, Stephanie H; Wittfeld, Katharina; Wolf, Christiane; Wolfers, Thomas; Wu, Jing Qin; Yasuda, Clarissa L; Zaremba, Dario; Zhang, Zuo; Zwiers, Marcel P; Artiges, Eric; Assareh, Amelia A; Ayesa-Arriola, Rosa; Belger, Aysenil; Brandt, Christine L; Brown, Gregory G; Cichon, Sven; Curran, Joanne E; Davies, Gareth E; Degenhardt, Franziska; Dennis, Michelle F; Dietsche, Bruno; Djurovic, Srdjan; Doherty, Colin P; Espiritu, Ryan; Garijo, Daniel; Gil, Yolanda; Gowland, Penny A; Green, Robert C; Häusler, Alexander N; Heindel, Walter; Ho, Beng-Choon; Hoffmann, Wolfgang U; Holsboer, Florian; Homuth, Georg; Hosten, Norbert; Jack, Clifford R; Jang, MiHyun; Jansen, Andreas; Kimbrel, Nathan A; Kolskår, Knut; Koops, Sanne; Krug, Axel; Lim, Kelvin O; Luykx, Jurjen J; Mathalon, Daniel H; Mather, Karen A; Mattay, Venkata S; Matthews, Sarah; Mayoral Van Son, Jaqueline; McEwen, Sarah C; Melle, Ingrid; Morris, Derek W; Mueller, Bryon A; Nauck, Matthias; Nordvik, Jan E; Nöthen, Markus M; O'Leary, Daniel S; Opel, Nils; Martinot, Marie-Laure Paillère; Pike, G Bruce; Preda, Adrian; Quinlan, Erin B; Rasser, Paul E; Ratnakar, Varun; Reppermund, Simone; Steen, Vidar M; Tooney, Paul A; Torres, Fábio R; Veltman, Dick J; Voyvodic, James T; Whelan, Robert; White, Tonya; Yamamori, Hidenaga; Adams, Hieab HH; Bis, Joshua C; Debette, Stephanie; Decarli, Charles; Fornage, Myriam; Gudnason, Vilmundur; Hofer, Edith; Ikram, M Arfan; Launer, Lenore; Longstreth, WT; Lopez, Oscar L; Mazoyer, Bernard; Mosley, Thomas H; Roshchupkin, Gennady V; Satizabal, Claudia L; Schmidt, Reinhold; Seshadri, Sudha; Yang, Qiong; Alzheimer’s Disease Neuroimaging Initiative; CHARGE Consortium; EPIGEN Consortium; IMAGEN Consortium; SYS Consortium; Parkinson’s Progression Markers Initiative; Alvim, Marina KM; Ames, David; Anderson, Tim J; Andreassen, Ole A; Arias-Vasquez, Alejandro; Bastin, Mark E; Baune, Bernhard T; Beckham, Jean C; Blangero, John; Boomsma, Dorret I; Brodaty, Henry; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Bustillo, Juan R; Cahn, Wiepke; Cairns, Murray J; Calhoun, Vince; Carr, Vaughan J; Caseras, Xavier; Caspers, Svenja; Cavalleri, Gianpiero L; Cendes, Fernando; Corvin, Aiden; Crespo-Facorro, Benedicto; Dalrymple-Alford, John C; Dannlowski, Udo; de Geus, Eco JC; Deary, Ian J; Delanty, Norman; Depondt, Chantal; Desrivières, Sylvane; Donohoe, Gary; Espeseth, Thomas; Fernández, Guillén; Fisher, Simon E; Flor, Herta; Forstner, Andreas J; Francks, Clyde; Franke, Barbara; Glahn, David C; Gollub, Randy L; Grabe, Hans J; Gruber, Oliver; Håberg, Asta K; Hariri, Ahmad R; Hartman, Catharina A; Hashimoto, Ryota; Heinz, Andreas; Henskens, Frans A; Hillegers, Manon HJ; Hoekstra, Pieter J; Holmes, Avram J; Hong, L Elliot; Hopkins, William D; Hulshoff Pol, Hilleke E; Jernigan, Terry L; Jönsson, Erik G; Kahn, René S; Kennedy, Martin A; Kircher, Tilo TJ; Kochunov, Peter; Kwok, John BJ; Le Hellard, Stephanie; Loughland, Carmel M; Martin, Nicholas G; Martinot, Jean-Luc; McDonald, Colm; McMahon, Katie L; Meyer-Lindenberg, Andreas; Michie, Patricia T; Morey, Rajendra A; Mowry, Bryan; Nyberg, Lars; Oosterlaan, Jaap; Ophoff, Roel A; Pantelis, Christos; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda WJH; Polderman, Tinca JC; Posthuma, Danielle; Rietschel, Marcella; Roffman, Joshua L; Rowland, Laura M; Sachdev, Perminder S; Sämann, Philipp G; Schall, Ulrich; Schumann, Gunter; Scott, Rodney J; Sim, Kang; Sisodiya, Sanjay M; Smoller, Jordan W; Sommer, Iris E; St Pourcain, Beate; Stein, Dan J; Toga, Arthur W; Trollor, Julian N; Van der Wee, Nic JA; van 't Ent, Dennis; Völzke, Henry; Walter, Henrik; Weber, Bernd; Weinberger, Daniel R; Wright, Margaret J; Zhou, Juan; Stein, Jason L; Thompson, Paul M; Medland, Sarah E; Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group
    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.