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1. Antiplatelet Therapy After Noncardioembolic Stroke An Individual Patient Data Network Meta-Analysis

Author

Greving, J.P. (Jacoba), Diener, H.C. (Hans Christoph), Reitsma, J.B. (Johannes), Bath, P.M., Csiba, L., Hacke, W. (Werner), Kappelle, L.J. (Jaap), Koudstaal, P.J. (Peter), Leys, D., Mas, J.L., Sacco, R.L. (Ralph), Algra, A. (Ale), Greving, J.P. (Jacoba), Diener, H.C. (Hans Christoph), Reitsma, J.B. (Johannes), Bath, P.M., Csiba, L., Hacke, W. (Werner), Kappelle, L.J. (Jaap), Koudstaal, P.J. (Peter), Leys, D., Mas, J.L., Sacco, R.L. (Ralph), and Algra, A. (Ale)

Abstract

Background and Purpose— We assessed the efficacy and safety of antiplatelet agents after noncardioembolic stroke or transient ischemic attack and examined how these vary according to patients’ demographic and clinical characteristics. Methods— We did a network meta-analysis (NMA) of data from 6 randomized trials of the effects of commonly prescribed antiplatelet agents in the long-term (≥3 months) secondary prevention of noncardioembolic stroke or transient ischemic attack. Individual patient data from 43 112 patients were pooled and reanalyzed. Main outcomes were serious vascular events (nonfatal stroke, nonfatal myocardial infarction, or vascular death), major bleeding, and net clinical benefit (serious vascular event or major bleeding). Subgroup analyses were done according to age, sex, ethnicity, hypertension, qualifying diagnosis, type of vessel involved (large versus small vessel disease), and time from qualifying event to randomization. Results— Aspirin/dipyridamole combination (RRNMA-adj, 0.83; 95% CI, 0.74–0.94) significantly reduced the risk of vascular events compared with aspirin, as did clopidogrel (RRNMA-adj, 0.88; 95% CI, 0.78–0.98), and aspirin/clopidogrel combination (RRNMA-adj, 0.83; 95% CI, 0.71–0.96). Clopidogrel caused significantly less major bleeding and intracranial hemorrhage than aspirin, aspirin/dipyridamole combination, and aspirin/clopidogrel combination. Aspirin/clopidogrel combination caused significantly more major bleeding than aspirin, aspirin/dipyridamole combination, and clopidogrel. Net clinical benefit was similar for clopidogrel and aspirin/dipyridamole combination (RRNMA-adj, 0.99; 95% CI, 0.93–1.05). Subgroup analyses showed no heterogeneity of treatment effectiveness across prespecified subgroups. The excess risk of major bleeding associated with aspirin/clopidogrel combination compared with clopidogrel alone was higher in patients aged <65 years than it was in patients ≥65 years (RRNMA-adj, 3.9 versus 1.7). Conclusions— Res

Published
2019
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2. Genetic variation at 16q24.2 is associated with small vessel stroke

Author

Traylor, M. (Matthew), Malik, R. (Rainer), Nalls, M.A. (Michael), Cotlarciuc, I. (Ioana), Radmanesh, F. (Farid), Thorleifsson, G. (Gudmar), Hanscombe, K.B. (Ken B.), Langefeld, C.D. (Carl), Saleheen, D. (Danish), Rost, N.S. (Natalia), Yet, I. (Idil), Spector, T.D. (Timothy), Bell, J.T. (Jordana), Hannon, E. (Eilis), Mill, J. (Jonathan), Chauhan, G. (Ganesh), Debette, S. (Stéphanie), Bis, J.C. (Joshua), Longstreth Jr, W.T., Ikram, M.K. (Kamran), Launer, L.J. (Lenore), Seshadri, S. (Sudha), Hamilton-Bruce, M.A. (Monica Anne), Jimenez-Conde, J. (Jordi), Cole, J.W. (John W.), Schmidt, R. (Reinhold), Slowik, A. (Agnieszka), Lemmens, R. (Robin), Lindgren, A.G. (Arne G.), Melander, O. (Olle), Grewal, R.P. (Raji P.), Sacco, R.L. (Ralph), Rundek, T. (Tatjana), Rexrode, K. (Kathryn), Arnett, D.K. (Donna), Johnson, J.A. (Julie A.), Benavente, O.R. (Oscar R.), Wasssertheil-Smoller, S. (Sylvia), Lee, J.-M. (Jin-Moo), Pulit, S.L. (Sara), Wong, Q. (Quenna), Rich, S.S. (Stephen), Bakker, P.I.W. (Paul) de, McArdle, P.F. (Patrick), Woo, D. (Daniel), Anderson, C.D. (Christopher D.), Xu, H. (Huichun), Heitsch, L. (Laura), Fornage, M. (Myriam), Jern, C. (Christina), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Gretarsdottir, S. (Solveig), Lewis, C.M. (Cathryn), Sharma, P. (Pankaj), Sudlow, C. (Cathie), Rothwell, P.M. (Peter), Boncoraglio, G. (Giorgio Battista), Thijs, V. (Vincent), Levi, C. (Christopher), Meschia, J.F. (James F.), Rosand, J. (Jonathan), Kittner, T. (Thomas), Mitchell, B.D. (Braxton), Kubisch, C. (Christian), Worrall, B.B. (Bradford B.), Markus, H.S. (Hugh), Traylor, M. (Matthew), Malik, R. (Rainer), Nalls, M.A. (Michael), Cotlarciuc, I. (Ioana), Radmanesh, F. (Farid), Thorleifsson, G. (Gudmar), Hanscombe, K.B. (Ken B.), Langefeld, C.D. (Carl), Saleheen, D. (Danish), Rost, N.S. (Natalia), Yet, I. (Idil), Spector, T.D. (Timothy), Bell, J.T. (Jordana), Hannon, E. (Eilis), Mill, J. (Jonathan), Chauhan, G. (Ganesh), Debette, S. (Stéphanie), Bis, J.C. (Joshua), Longstreth Jr, W.T., Ikram, M.K. (Kamran), Launer, L.J. (Lenore), Seshadri, S. (Sudha), Hamilton-Bruce, M.A. (Monica Anne), Jimenez-Conde, J. (Jordi), Cole, J.W. (John W.), Schmidt, R. (Reinhold), Slowik, A. (Agnieszka), Lemmens, R. (Robin), Lindgren, A.G. (Arne G.), Melander, O. (Olle), Grewal, R.P. (Raji P.), Sacco, R.L. (Ralph), Rundek, T. (Tatjana), Rexrode, K. (Kathryn), Arnett, D.K. (Donna), Johnson, J.A. (Julie A.), Benavente, O.R. (Oscar R.), Wasssertheil-Smoller, S. (Sylvia), Lee, J.-M. (Jin-Moo), Pulit, S.L. (Sara), Wong, Q. (Quenna), Rich, S.S. (Stephen), Bakker, P.I.W. (Paul) de, McArdle, P.F. (Patrick), Woo, D. (Daniel), Anderson, C.D. (Christopher D.), Xu, H. (Huichun), Heitsch, L. (Laura), Fornage, M. (Myriam), Jern, C. (Christina), Zwart, J-A. (John-Anker), Thorsteinsdottir, U. (Unnur), Gretarsdottir, S. (Solveig), Lewis, C.M. (Cathryn), Sharma, P. (Pankaj), Sudlow, C. (Cathie), Rothwell, P.M. (Peter), Boncoraglio, G. (Giorgio Battista), Thijs, V. (Vincent), Levi, C. (Christopher), Meschia, J.F. (James F.), Rosand, J. (Jonathan), Kittner, T. (Thomas), Mitchell, B.D. (Braxton), Kubisch, C. (Christian), Worrall, B.B. (Bradford B.), and Markus, H.S. (Hugh)

Abstract

Objective: Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises one quarter of all ischemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown that younger-onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger-onset SVS population, to identify novel associations with stroke. Methods: We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on messenger RNA (mRNA) expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain. Results: We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (odds ratio [OR; 95% confidence interval {CI}] = 1.16 [1.10–1.22]; p = 3.2 × 10−9). The lead single-nucleotide polymorphism (rs12445022) was also associated with cerebral white matter hyperintensities (OR [95% CI] = 1.10 [1.05–1.16]; p = 5.3 × 10−5; N = 3,670), but not intracerebral hemorrhage (OR [95% CI] = 0.97 [0.84–1.12]; p = 0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p = 9.4 × 10−7) and DNA methylation at probe cg16596957

Published
2017
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3. Automatic identification of variables in epidemiological datasets using logic regression

Author

Lorenz, M.W. (Matthias W.), Abdi, N.A. (Negin Ashtiani), Scheckenbach, F. (Frank), Pflug, A. (Anja), Bulbul, A. (Alpaslan), Catapano, A.L. (Alberico), Agewall, S. (Stefan), Ezhov, M. (Marat), Bots, M.L. (Michiel), Kiechl, S. (Stefan), Orth, A. (Andreas), Norata, G.D. (Giuseppe), Empana, J.P. (Jean Philippe), Lin, H.-J. (Hung-Ju), McLachlan, S. (Stela), Bokemark, L. (Lena), Ronkainen, K. (Kimmo), Amato, M. (Mauro), Schminke, U. (Ulf), Srinivasan, S.R. (Sathanur R.), Lind, L. (Lars), Kato, A. (Akihiko), Dimitriadis, C. (Chrystosomos), Przewlocki, T. (Tadeusz), Okazaki, S. (Shuhei), Stehouwer, C.D. (Coen), Lazarevic, T. (Tatjana), Willeit, J. (Johann), Yanez, D.N. (David N.), Steinmetz, H. (helmuth), Sander, D. (Dirk), Poppert, H. (Holger), Desvarieux, M. (Moise), Ikram, M.A. (Arfan), Bevc, S. (Sebastjan), Staub, D. (Daniel), Sirtori, C.R. (Cesare R.), Iglseder, B. (Bernhard), Engström, G., Tripepi, G.L. (Giovanni), Beloqui, O. (Oscar), Lee, M.-S. (Moo-Sik), Friera, A. (Alfonsa), Xie, W. (Wuxiang), Grigore, L. (Liliana), Plichart, M. (Matthieu), Su, T.-C. (Ta-Chen), Robertson, C.M. (Christine M), Schmidt, C. (Caroline), Tuomainen, T.-P. (Tomi-Pekka), Veglia, F. (Fabrizio), Völzke, H. (Henry), Nijpels, M.G.A.A.M. (Giel), Jovanovic, A. (Aleksandar), Sacco, R.L. (Ralph L.), Franco, O.H. (Oscar), Hojs, R. (Radovan), Uthoff, H. (Heiko), Hedblad, B. (Bo), Park, H.W. (Hyun Woong), Suarez, C. (Carmen), Zhao, D. (Dong), Catapano, A. (Alberico), Ducimetiere, P. (P.), Chien, K.-L. (Kuo-Liong), Price, J.F. (Jackie F.), Bergstrom, G. (Goran), Kauhanen, J. (Jussi), Tremoli, E. (Elena), Dörr, M. (Marcus), Berenson, G. (Gerald), Papagianni, A. (Aikaterini), Kablak-Ziembicka, A. (Anna), Kitagawa, K. (Kazuo), Dekker, J.M. (Jacqueline), Stolic, R. (Radojica), Polak, J.F. (Joseph F.), Sitzer, M. (Matthias), Bickel, H. (Horst), Rundek, T. (Tatjana), Hofman, A. (Albert), Ekart, R. (Robert), Frauchiger, B. (Beat), Castelnuovo, S. (Samuela), Rosvall, M. (Maria), Zoccali, C. (Carmine), Landecho, M.F. (Manuel F.), Bae, J.-H. (Jang-Ho), Gabriel, R. (Rafael), Liu, J. (Jing), Baldassarre, D. (Damiano), Kavousi, M. (Maryam), Lorenz, M.W. (Matthias W.), Abdi, N.A. (Negin Ashtiani), Scheckenbach, F. (Frank), Pflug, A. (Anja), Bulbul, A. (Alpaslan), Catapano, A.L. (Alberico), Agewall, S. (Stefan), Ezhov, M. (Marat), Bots, M.L. (Michiel), Kiechl, S. (Stefan), Orth, A. (Andreas), Norata, G.D. (Giuseppe), Empana, J.P. (Jean Philippe), Lin, H.-J. (Hung-Ju), McLachlan, S. (Stela), Bokemark, L. (Lena), Ronkainen, K. (Kimmo), Amato, M. (Mauro), Schminke, U. (Ulf), Srinivasan, S.R. (Sathanur R.), Lind, L. (Lars), Kato, A. (Akihiko), Dimitriadis, C. (Chrystosomos), Przewlocki, T. (Tadeusz), Okazaki, S. (Shuhei), Stehouwer, C.D. (Coen), Lazarevic, T. (Tatjana), Willeit, J. (Johann), Yanez, D.N. (David N.), Steinmetz, H. (helmuth), Sander, D. (Dirk), Poppert, H. (Holger), Desvarieux, M. (Moise), Ikram, M.A. (Arfan), Bevc, S. (Sebastjan), Staub, D. (Daniel), Sirtori, C.R. (Cesare R.), Iglseder, B. (Bernhard), Engström, G., Tripepi, G.L. (Giovanni), Beloqui, O. (Oscar), Lee, M.-S. (Moo-Sik), Friera, A. (Alfonsa), Xie, W. (Wuxiang), Grigore, L. (Liliana), Plichart, M. (Matthieu), Su, T.-C. (Ta-Chen), Robertson, C.M. (Christine M), Schmidt, C. (Caroline), Tuomainen, T.-P. (Tomi-Pekka), Veglia, F. (Fabrizio), Völzke, H. (Henry), Nijpels, M.G.A.A.M. (Giel), Jovanovic, A. (Aleksandar), Sacco, R.L. (Ralph L.), Franco, O.H. (Oscar), Hojs, R. (Radovan), Uthoff, H. (Heiko), Hedblad, B. (Bo), Park, H.W. (Hyun Woong), Suarez, C. (Carmen), Zhao, D. (Dong), Catapano, A. (Alberico), Ducimetiere, P. (P.), Chien, K.-L. (Kuo-Liong), Price, J.F. (Jackie F.), Bergstrom, G. (Goran), Kauhanen, J. (Jussi), Tremoli, E. (Elena), Dörr, M. (Marcus), Berenson, G. (Gerald), Papagianni, A. (Aikaterini), Kablak-Ziembicka, A. (Anna), Kitagawa, K. (Kazuo), Dekker, J.M. (Jacqueline), Stolic, R. (Radojica), Polak, J.F. (Joseph F.), Sitzer, M. (Matthias), Bickel, H. (Horst), Rundek, T. (Tatjana), Hofman, A. (Albert), Ekart, R. (Robert), Frauchiger, B. (Beat), Castelnuovo, S. (Samuela), Rosvall, M. (Maria), Zoccali, C. (Carmine), Landecho, M.F. (Manuel F.), Bae, J.-H. (Jang-Ho), Gabriel, R. (Rafael), Liu, J. (Jing), Baldassarre, D. (Damiano), and Kavousi, M. (Maryam)

Abstract

Background: For an individual participant data (IPD) meta-analysis, multiple datasets must be transformed in a consistent format, e.g. using uniform variable names. When large numbers of datasets have to be processed, this can be a time-consuming and error-prone task. Automated or semi-automated identification of variables can help to reduce the workload and improve the data quality. For semi-automation high sensitivity in the recognition of matching variables is particularly important, because it allows creating software which for a target variable presents a choice of source variables, from which a user can choose the matching one, with only low risk of having missed a correct source variable. Methods: For each variable in a set of target variables, a number of simple rules were manually created. With logic regression, an optimal Boolean combination of these rules was searched for every target variable, using a random subset of a large database of epidemiological and clinical cohort data (construction subset). In a second subset of this database (validation subset), this optimal combination rules were validated. Results: In the construction sample, 41 target variables were allocated on average with a positive predictive value (PPV) of 34%, and a negative predictive value (NPV) of 95%. In the validation sample, PPV was 33%, whereas NPV remained at 94%. In the construction sample, PPV was 50% or less in 63% of all variables, in the validation sample in 71% of all variables. Conclusions: We demonstrated that the application of logic regression in a complex data management task in large epidemiological IPD meta-analyses is feasible. However, the performance of the algorithm is poor, which may require backup strategies.

Published
2017
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4. Novel genetic loci associated with hippocampal volume

Author

Hibar, D.P. (Derrek), Adams, H.H.H. (Hieab), Jahanshad, N. (Neda), Chauhan, G. (Ganesh), Stein, J.L., Hofer, E. (Edith), Rentería, M.E. (Miguel), Bis, J.C. (Joshua), Arias-Vásquez, A. (Alejandro), Ikram, M.K. (M. Kamran), Desrivières, S. (Sylvane), Vernooij, M.W. (Meike), Abramovic, L. (Lucija), Alhusaini, S. (Saud), Amin, N. (Najaf), Andersson, M. (Micael), Arfanakis, K. (Konstantinos), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Athanasiu, L. (Lavinia), Axelsson, T. (Tomas), Beecham, A.H. (Ashley), Beiser, A. (Alexa), Bernard, M. (Manon), Blanton, S.H. (Susan H.), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brickman, A.M. (Adam M.), Carmichael, O. (Owen), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Chouraki, V. (Vincent), Cuellar-Partida, G. (Gabriel), Crivello, F. (Fabrice), Braber, A. (Anouk) den, Doan, N.T. (Nhat Trung), Ehrlich, S.M. (Stefan), Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Gottesman, R.F. (Rebecca), Grimm, O. (Oliver), Griswold, M.D. (Michael), Guadalupe, T. (Tulio), Gutman, B.A. (Boris A.), Hass, J. (Johanna), Haukvik, U.K. (Unn), Hoehn, D. (David), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Jørgensen, K.N. (Kjetil N.), Karbalai, N. (Nazanin), Kasperaviciute, D. (Dalia), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Luciano, M. (Michelle), MacAre, C. (Christine), Marquand, A.F. (Andre F.), Matarin, M. (Mar), Mather, R., Mattheisen, M. (Manuel), McKay, D.R. (David R.), Milaneschi, Y. (Yuri), Muñoz Maniega, S. (Susana), Nho, K. (Kwangsik), Nugent, A.C. (Allison), Nyquist, P. (Paul), Loohuis, L.M.O. (Loes M. Olde), Oosterlaan, J. (Jaap), Papmeyer, M. (Martina), Pirpamer, L. (Lukas), Pütz, B. (Benno), Ramasamy, A. (Adaikalavan), Richards, J.S. (Jennifer S.), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rommelse, N. (Nanda), Ropele, S. (Stefan), Rose, E.J. (Emma), Royle, N.A. (Natalie), Rundek, T. (Tatjana), Sämann, P.G. (Philipp), Saremi, A. (Arvin), Satizabal, C.L. (Claudia), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shen, L. (Li), Shin, J. (Jean), Shumskaya, E. (Elena), Smith, A.V. (Albert Vernon), Sprooten, R. (Roy), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Tordesillas-Gutierrez, D. (Diana), Toro, R. (Roberto), Trabzuni, D. (Danyah), Trompet, S. (Stella), Vaidya, D. (Dhananjay), van der Grond, J. (Jeroen), Lee, S.J. (Sven) van der, Van Der Meer, D. (Dennis), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Erp, T.G.M. (Theo G.) van, Van Rooij, D. (Daan), Walton, E. (Esther), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Windham, B.G. (Gwen), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Woldehawariat, G. (Girma), Björnsson, A. (Asgeir), Wolfers, T. (Thomas), Yanek, L.R. (Lisa), Yang, J. (Jingyun), Zijdenbos, A.P., Zwiers, M.P. (Marcel), Agartz, I. (Ingrid), Almasy, L. (Laura), Ames, D.J. (David), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Arepalli, S. (Sampath), Assareh, A.A., Barral, S. (Sandra), Bastin, M.E. (Mark), Becker, D.M. (Diane M.), Becker, J.T. (James), Bennett, D.A. (David A.), Blangero, J. (John), Bokhoven, H. (Hans) van, Boomsma, D.I. (Dorret), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan), Bulayeva, K. (Kazima), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D.M. (Dara), Cavalleri, G. (Gianpiero), Cheng, C.-Y. (Ching-Yu), Cichon, S. (Sven), Cookson, M.R. (Mark), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Curran, J.E. (Joanne), Czisch, M. (Michael), Dale, A.M. (Anders), Davies, G.E. (Gareth), Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Jager, P.L. (Philip) de, Zubicaray, G.I. (Greig) de, Deary, I.J. (Ian), Debette, S. (Stéphanie), DeCarli, C. (Charles), Delanty, N., Depondt, C. (Chantal), DeStefano, A.L. (Anita), Dillman, A. (Allissa), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drevets, D.A. (Douglas), Duggirala, R. (Ravi), Dyer, M.D. (Matthew), Enzinger, C. (Christian), Erk, S., Espeseth, T. (Thomas), Fedko, I.O. (Iryna O.), Fernández, G. (Guillén), Ferrucci, L. (Luigi), Fisher, S.E. (Simon), Fleischman, D. (Debra), Ford, I. (Ian), Fornage, M. (Myriam), Foroud, T. (Tatiana), Fox, P.T. (Peter), Francks, C. (Clyde), Fukunaga, M. (Masaki), Gibbs, J.R. (J. Raphael), Glahn, D.C. (David), Gollub, R.L. (Randy), Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Gruber, O. (Oliver), Gudnason, V. (Vilmundur), Guelfi, S. (Sebastian), Håberg, A.K. (Asta K.), Hansell, N.K. (Narelle), Hardy, J. (John), Hartman, C.A. (C.), Hashimoto, R. (Ryota), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Le Hellard, S. (Stephanie), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Holsboer, F. (Florian), Homuth, G. (Georg), Hosten, N. (Norbert), Hottenga, J.J. (Jouke Jan), Huentelman, M.J. (Matthew), Pol, H.H., Ikeda, M. (Masashi), Jack, C.R. (Clifford R.), Jenkinson, S. (Sarah), Johnson, R. (Robert), Jönsson, E.G. (Erik G.), Jukema, J.W., Kahn, R. (René), Kanai, R. (Ryota), Kloszewska, I. (Iwona), Knopman, D.S. (David S.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Lemaître, H. (Herve), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Lopez, O.L. (Oscar L.), Lovestone, S. (Simon), Martinez, O. (Oliver), Martinot, J.-L. (Jean-Luc), Mattay, V.S. (Venkata S.), McDonald, C. (Colm), McIntosh, A.M. (Andrew), McMahon, F.J. (Francis J.), McMahon, K.L. (Katie L.), Mecocci, P. (Patrizia), Melle, I. (Ingrid), Meyer-Lindenberg, A. (Andreas), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant W.), Morris, D.W. (Derek W), Mosley, T.H. (Thomas H.), Mühleisen, T.W. (Thomas), Müller-Myhsok, B. (B.), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nichols, T.E. (Thomas), Niessen, W.J. (Wiro), Nöthen, M.M. (Markus), Nyberg, L. (Lars), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Ophoff, R.A. (Roel), Pandolfo, M. (Massimo), Paus, T. (Tomas), Pausova, Z. (Zdenka), Penninx, B.W.J.H. (Brenda), Pike, G.B. (G. Bruce), Potkin, S.G. (Steven), Psaty, B.M. (Bruce), Reppermund, S., Rietschel, M. (Marcella), Roffman, J.L. (Joshua), Seiferth, N. (Nina), Rotter, J.I. (Jerome I.), Ryten, M. (Mina), Sacco, R.L. (Ralph L.), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, C.J. (Christopher), Sigursson, S. (Sigurdur), Simmons, A. (Andrew), Singleton, A. (Andrew), Sisodiya, S.M. (Sanjay), Smith, C. (Colin), Smoller, J.W., Soininen, H. (H.), Steen, V.M. (Vidar), Stott, D.J. (David J.), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Tsolaki, M. (Magda), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Hernández, M.C.V. (Maria C. Valdés), Brug, M.P. (Marcel) van der, Lugt, A. (Aad) van der, Wee, N.J. (Nic) van der, Haren, N.E.M. (Neeltje E.) van, Ent, D. (Dennis) van 't, Tol, M.J.D. (Marie-José) van, Vardarajan, B.N. (Badri), Vellas, B. (Bruno), Veltman, D.J. (Dick), Völzke, H. (Henry), Walter, H.J. (Henrik), Wardlaw, J. (Joanna), Wassink, A.M.J. (Annemarie), Weale, M.E. (Michael), Weinberger, D.R. (Daniel R.), Weiner, M.W. (Michael W.), Wen, W. (Wei), Westman, E. (Eric), White, T.J.H. (Tonya), Wong, T.Y. (Tien Y.), Wright, C.B. (Clinton B.), Zielke, R.H. (Ronald H.), Zonderman, A.B., Martin, N.G. (Nicholas), Duijn, C.M. (Cornelia) van, Wright, M.J. (Margaret), Longstreth Jr, W.T., Schumann, G. (Gunter), Grabe, H.J. (Hans Jörgen), Franke, B. (Barbara), Launer, L.J. (Lenore), Medland, S.E. (Sarah), Seshadri, S. (Sudha), Thompson, P.M. (Paul), Ikram, M.K. (Kamran), Hibar, D.P. (Derrek), Adams, H.H.H. (Hieab), Jahanshad, N. (Neda), Chauhan, G. (Ganesh), Stein, J.L., Hofer, E. (Edith), Rentería, M.E. (Miguel), Bis, J.C. (Joshua), Arias-Vásquez, A. (Alejandro), Ikram, M.K. (M. Kamran), Desrivières, S. (Sylvane), Vernooij, M.W. (Meike), Abramovic, L. (Lucija), Alhusaini, S. (Saud), Amin, N. (Najaf), Andersson, M. (Micael), Arfanakis, K. (Konstantinos), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Athanasiu, L. (Lavinia), Axelsson, T. (Tomas), Beecham, A.H. (Ashley), Beiser, A. (Alexa), Bernard, M. (Manon), Blanton, S.H. (Susan H.), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brickman, A.M. (Adam M.), Carmichael, O. (Owen), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Chouraki, V. (Vincent), Cuellar-Partida, G. (Gabriel), Crivello, F. (Fabrice), Braber, A. (Anouk) den, Doan, N.T. (Nhat Trung), Ehrlich, S.M. (Stefan), Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Gottesman, R.F. (Rebecca), Grimm, O. (Oliver), Griswold, M.D. (Michael), Guadalupe, T. (Tulio), Gutman, B.A. (Boris A.), Hass, J. (Johanna), Haukvik, U.K. (Unn), Hoehn, D. (David), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Jørgensen, K.N. (Kjetil N.), Karbalai, N. (Nazanin), Kasperaviciute, D. (Dalia), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Luciano, M. (Michelle), MacAre, C. (Christine), Marquand, A.F. (Andre F.), Matarin, M. (Mar), Mather, R., Mattheisen, M. (Manuel), McKay, D.R. (David R.), Milaneschi, Y. (Yuri), Muñoz Maniega, S. (Susana), Nho, K. (Kwangsik), Nugent, A.C. (Allison), Nyquist, P. (Paul), Loohuis, L.M.O. (Loes M. Olde), Oosterlaan, J. (Jaap), Papmeyer, M. (Martina), Pirpamer, L. (Lukas), Pütz, B. (Benno), Ramasamy, A. (Adaikalavan), Richards, J.S. (Jennifer S.), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rommelse, N. (Nanda), Ropele, S. (Stefan), Rose, E.J. (Emma), Royle, N.A. (Natalie), Rundek, T. (Tatjana), Sämann, P.G. (Philipp), Saremi, A. (Arvin), Satizabal, C.L. (Claudia), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shen, L. (Li), Shin, J. (Jean), Shumskaya, E. (Elena), Smith, A.V. (Albert Vernon), Sprooten, R. (Roy), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Tordesillas-Gutierrez, D. (Diana), Toro, R. (Roberto), Trabzuni, D. (Danyah), Trompet, S. (Stella), Vaidya, D. (Dhananjay), van der Grond, J. (Jeroen), Lee, S.J. (Sven) van der, Van Der Meer, D. (Dennis), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Erp, T.G.M. (Theo G.) van, Van Rooij, D. (Daan), Walton, E. (Esther), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Windham, B.G. (Gwen), Winkler, A.M. (Anderson), Wittfeld, K. (Katharina), Woldehawariat, G. (Girma), Björnsson, A. (Asgeir), Wolfers, T. (Thomas), Yanek, L.R. (Lisa), Yang, J. (Jingyun), Zijdenbos, A.P., Zwiers, M.P. (Marcel), Agartz, I. (Ingrid), Almasy, L. (Laura), Ames, D.J. (David), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Arepalli, S. (Sampath), Assareh, A.A., Barral, S. (Sandra), Bastin, M.E. (Mark), Becker, D.M. (Diane M.), Becker, J.T. (James), Bennett, D.A. (David A.), Blangero, J. (John), Bokhoven, H. (Hans) van, Boomsma, D.I. (Dorret), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan), Bulayeva, K. (Kazima), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D.M. (Dara), Cavalleri, G. (Gianpiero), Cheng, C.-Y. (Ching-Yu), Cichon, S. (Sven), Cookson, M.R. (Mark), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Curran, J.E. (Joanne), Czisch, M. (Michael), Dale, A.M. (Anders), Davies, G.E. (Gareth), Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Jager, P.L. (Philip) de, Zubicaray, G.I. (Greig) de, Deary, I.J. (Ian), Debette, S. (Stéphanie), DeCarli, C. (Charles), Delanty, N., Depondt, C. (Chantal), DeStefano, A.L. (Anita), Dillman, A. (Allissa), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drevets, D.A. (Douglas), Duggirala, R. (Ravi), Dyer, M.D. (Matthew), Enzinger, C. (Christian), Erk, S., Espeseth, T. (Thomas), Fedko, I.O. (Iryna O.), Fernández, G. (Guillén), Ferrucci, L. (Luigi), Fisher, S.E. (Simon), Fleischman, D. (Debra), Ford, I. (Ian), Fornage, M. (Myriam), Foroud, T. (Tatiana), Fox, P.T. (Peter), Francks, C. (Clyde), Fukunaga, M. (Masaki), Gibbs, J.R. (J. Raphael), Glahn, D.C. (David), Gollub, R.L. (Randy), Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Gruber, O. (Oliver), Gudnason, V. (Vilmundur), Guelfi, S. (Sebastian), Håberg, A.K. (Asta K.), Hansell, N.K. (Narelle), Hardy, J. (John), Hartman, C.A. (C.), Hashimoto, R. (Ryota), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Le Hellard, S. (Stephanie), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Holsboer, F. (Florian), Homuth, G. (Georg), Hosten, N. (Norbert), Hottenga, J.J. (Jouke Jan), Huentelman, M.J. (Matthew), Pol, H.H., Ikeda, M. (Masashi), Jack, C.R. (Clifford R.), Jenkinson, S. (Sarah), Johnson, R. (Robert), Jönsson, E.G. (Erik G.), Jukema, J.W., Kahn, R. (René), Kanai, R. (Ryota), Kloszewska, I. (Iwona), Knopman, D.S. (David S.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Lemaître, H. (Herve), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Lopez, O.L. (Oscar L.), Lovestone, S. (Simon), Martinez, O. (Oliver), Martinot, J.-L. (Jean-Luc), Mattay, V.S. (Venkata S.), McDonald, C. (Colm), McIntosh, A.M. (Andrew), McMahon, F.J. (Francis J.), McMahon, K.L. (Katie L.), Mecocci, P. (Patrizia), Melle, I. (Ingrid), Meyer-Lindenberg, A. (Andreas), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant W.), Morris, D.W. (Derek W), Mosley, T.H. (Thomas H.), Mühleisen, T.W. (Thomas), Müller-Myhsok, B. (B.), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nichols, T.E. (Thomas), Niessen, W.J. (Wiro), Nöthen, M.M. (Markus), Nyberg, L. (Lars), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Ophoff, R.A. (Roel), Pandolfo, M. (Massimo), Paus, T. (Tomas), Pausova, Z. (Zdenka), Penninx, B.W.J.H. (Brenda), Pike, G.B. (G. Bruce), Potkin, S.G. (Steven), Psaty, B.M. (Bruce), Reppermund, S., Rietschel, M. (Marcella), Roffman, J.L. (Joshua), Seiferth, N. (Nina), Rotter, J.I. (Jerome I.), Ryten, M. (Mina), Sacco, R.L. (Ralph L.), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, C.J. (Christopher), Sigursson, S. (Sigurdur), Simmons, A. (Andrew), Singleton, A. (Andrew), Sisodiya, S.M. (Sanjay), Smith, C. (Colin), Smoller, J.W., Soininen, H. (H.), Steen, V.M. (Vidar), Stott, D.J. (David J.), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Tsolaki, M. (Magda), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Hernández, M.C.V. (Maria C. Valdés), Brug, M.P. (Marcel) van der, Lugt, A. (Aad) van der, Wee, N.J. (Nic) van der, Haren, N.E.M. (Neeltje E.) van, Ent, D. (Dennis) van 't, Tol, M.J.D. (Marie-José) van, Vardarajan, B.N. (Badri), Vellas, B. (Bruno), Veltman, D.J. (Dick), Völzke, H. (Henry), Walter, H.J. (Henrik), Wardlaw, J. (Joanna), Wassink, A.M.J. (Annemarie), Weale, M.E. (Michael), Weinberger, D.R. (Daniel R.), Weiner, M.W. (Michael W.), Wen, W. (Wei), Westman, E. (Eric), White, T.J.H. (Tonya), Wong, T.Y. (Tien Y.), Wright, C.B. (Clinton B.), Zielke, R.H. (Ronald H.), Zonderman, A.B., Martin, N.G. (Nicholas), Duijn, C.M. (Cornelia) van, Wright, M.J. (Margaret), Longstreth Jr, W.T., Schumann, G. (Gunter), Grabe, H.J. (Hans Jörgen), Franke, B. (Barbara), Launer, L.J. (Lenore), Medland, S.E. (Sarah), Seshadri, S. (Sudha), Thompson, P.M. (Paul), and Ikram, M.K. (Kamran)

Abstract

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Published
2017
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5. Carotid Intima-Media thickness progression and risk of vascular events in people with Diabetes: Results from the PROG-IMT collaboration

Author

Lorenz, M.W. (Matthias), Price, J.F. (Jackie F.), Robertson, C.M. (Christine M), Bots, M.L. (Michiel), Polak, J.F. (Joseph F.), Poppert, H. (Holger), Kavousi, M. (Maryam), Dörr, M. (Marcus), Stensland, E. (Eva), Ducimetiere, P. (Pierre), Ronkainen, K. (Kimmo), Kiechl, S. (Stefan), Sitzer, M. (Matthias), Rundek, T. (Tatjana), Lind, L. (Lars), Liu, J. (Jing), Bergstrom, G. (Goran), Grigore, L. (Liliana), Bokemark, L. (Lena), Friera, A. (Alfonsa), Yanez, D. (David), Bickel, H. (Horst), Ikram, M.A. (Arfan), Volzke, H. (Henry), Johnsen, S.H., Empana, J.P. (Jean Philippe), Tuomainen, T.-P. (Tomi-Pekka), Willeit, J. (Johann), Steinmetz, H. (Helmuth), Desvarieux, M. (Moise), Xie, W. (Wuxiang), Schmidt, C. (Caroline), Norata, G.D. (Giuseppe), Suárez, C. (Carmen), Sander, D. (Dirk), Hofman, A. (Albert), Schminke, U. (Ulf), Mathiesen, E.B. (Ellisiv), Plichart, M. (Matthieu), Kauhanen, J. (Jussi), Sacco, R.L. (Ralph), McLachlan, S. (Stela), Zhao, D. (Dong), Fagerberg, B. (Bjorn), Catapano, A.L. (Alberico L.), Gabriel, R. (Rafael), Franco, O.H. (Oscar), Bulbul, A. (Alpaslan), Scheckenbach, F. (Frank), Pflug, A. (Anja), Gao, L. (Lu), Thompson, S.G. (Simon G.), Lorenz, M.W. (Matthias), Price, J.F. (Jackie F.), Robertson, C.M. (Christine M), Bots, M.L. (Michiel), Polak, J.F. (Joseph F.), Poppert, H. (Holger), Kavousi, M. (Maryam), Dörr, M. (Marcus), Stensland, E. (Eva), Ducimetiere, P. (Pierre), Ronkainen, K. (Kimmo), Kiechl, S. (Stefan), Sitzer, M. (Matthias), Rundek, T. (Tatjana), Lind, L. (Lars), Liu, J. (Jing), Bergstrom, G. (Goran), Grigore, L. (Liliana), Bokemark, L. (Lena), Friera, A. (Alfonsa), Yanez, D. (David), Bickel, H. (Horst), Ikram, M.A. (Arfan), Volzke, H. (Henry), Johnsen, S.H., Empana, J.P. (Jean Philippe), Tuomainen, T.-P. (Tomi-Pekka), Willeit, J. (Johann), Steinmetz, H. (Helmuth), Desvarieux, M. (Moise), Xie, W. (Wuxiang), Schmidt, C. (Caroline), Norata, G.D. (Giuseppe), Suárez, C. (Carmen), Sander, D. (Dirk), Hofman, A. (Albert), Schminke, U. (Ulf), Mathiesen, E.B. (Ellisiv), Plichart, M. (Matthieu), Kauhanen, J. (Jussi), Sacco, R.L. (Ralph), McLachlan, S. (Stela), Zhao, D. (Dong), Fagerberg, B. (Bjorn), Catapano, A.L. (Alberico L.), Gabriel, R. (Rafael), Franco, O.H. (Oscar), Bulbul, A. (Alpaslan), Scheckenbach, F. (Frank), Pflug, A. (Anja), Gao, L. (Lu), and Thompson, S.G. (Simon G.)

Abstract

OBJECTIVE Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes. RESEARCH DESIGN AND MET

Published
2015
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