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3. Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Author

Sims, R., van der Lee, S.J., Naj, A.C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B.W., Boland, A., Raybould, R., Bis, J.C., Martin, E.R., Grenier-Boley, B., Heilmann-Heimbach, S., Chouraki, V., Kuzma, A.B., Sleegers, K., Vronskaya, M., Ruiz, A., Graham, R.R., Olaso, R., Hoffmann, P., Grove, M.L., Vardarajan, B.N., Hiltunen, M., Nöthen, M.M., White, C.C., Hamilton-Nelson, K.L., Epelbaum, J., Maier, W., Choi, S.H., Beecham, G.W., Dulary, C., Herms, S., Smith, A.V., Funk, C.C., Derbois, Forstner, A.J., Ahmad, S., Li, H., Bacq, D., Harold, D., Satizabal, C.L., Valladares, O., Squassina, A., Thomas, R., Brody, J.A., Qu, L., Sánchez-Juan, P., Morgan, T., Wolters, F.J., Zhao, Y., Garcia, F.S., Denning, N., Fornage, M., Malamon, J., Naranjo, M.C.D., Majounie, E., Mosley, T.H., Dombroski, B., Wallon, D., Lupton, M.K., Dupuis, J., Whitehead, P., Fratiglioni, L., Medway, C., Jian, X., Mukherjee, S., Keller, L., Brown, K., Lin, H., Cantwell, L.B., Panza, F., McGuinness, B., Moreno-Grau, S., Burgess, J.D., Solfrizzi, V., Proitsi, P., Adams, H.H., Allen, M., Seripa, D., Pastor, P., Cupples, L.A., Price, N.D., Hannequin, D., Frank-García, A., Levy, D., Chakrabarty, P., Caffarra, P., Giegling, I., Beiser, A.S., Giedraitis, V., Hampel, H., Garcia, M.E., Wang, X., Lannfelt, L., Mecocci, P., Eiriksdottir, G., Crane, P.K., Pasquier, F., Boccardi, V., Henández, I., Barber, R.C., Scherer, M., Tarraga, L., Adams, P.M., Leber, M., Chen, Y., Albert, M.S., Riedel-Heller, S., Emilsson, V., Beekly, D., Braae, A., Schmidt, R., Blacker, D., Masullo, C., Schmidt, H., Doody, R.S., Spalletta, G., Longstreth, W.T., Jr., Fairchild, T.J., Bossù, P., Lopez, O.L., Frosch, M.P., Sacchinelli, E., Ghetti, B., Yang, Q., Huebinger, R.M., Jessen, F., Li, S., Kamboh, M.I., Morris, J., Sotolongo-Grau, O., Katz, M.J., Corcoran, C., Dunstan, M., Braddel, A., Thomas, C., Meggy, A., Marshall, R., Gerrish, A., Chapman, J., Aguilar, M., Taylor, S., Hill, M., Fairén, M.D., Hodges, A., Vellas, B., Soininen, H., Kloszewska, I., Daniilidou, M., Uphill, J., Patel, Y., Hughes, J.T., Lord, J., Turton, J., Hartmann, A.M., Cecchetti, R., Fenoglio, C., Serpente, M., Arcaro, M., Caltagirone, C., Orfei, M.D., Ciaramella, A., Pichler, S., Mayhaus, M., Gu, W., Lleó, A., Fortea, J., Blesa, R., Barber, I.S., Brookes, K., Cupidi, C., Maletta, R.G., Carrell, D., Sorbi, S., Moebus, S., Urbano, M., Pilotto, A., Kornhuber, J., Bosco, P., Todd, S., Craig, D., Johnston, J., Gill, M., Lawlor, B., Lynch, A., Fox, N.C., Hardy, J., Albin, R.L., Apostolova, L.G., Arnold, S.E., Asthana, S., Atwood, C.S., Baldwin, C.T., Barnes, L.L., Barral, S., Beach, T.G., Becker, J.T., Bigio, E.H., Bird, T.D., Boeve, B.F., Bowen, J.D., Boxer, A., Burke, J.R., Burns, J.M., Buxbaum, J.D., Cairns, N.J., Cao, C., Carlson, C.S., Carlsson, C.M., Carney, R.M., Carrasquillo, M.M., Carroll, S.L., Diaz, C.C., Chui, H.C., Clark, D.G., Cribbs, D.H., Crocco, E.A., DeCarli, C., Dick, M., Duara, R., Evans, D.A., Faber, K.M., Fallon, K.B., Fardo, D.W., Farlow, M.R., Ferris, S., Foroud, T.M., Galasko, D.R., Gearing, M., Geschwind, D.H., Gilbert, J.R., Graff-Radford, N.R., Green, R.C., Growdon, J.H., Hamilton, R.L., Harrell, L.E., Honig, L.S., Huentelman, M.J., Hulette, C.M., Hyman, B.T., Jarvik, G.P., Abner, E., Jin, L.W., Jun, G., Karydas, A., Kaye, J.A., Kim, R., Kowall, N.W., Kramer, J.H., LaFerla, F.M., Lah, J.J., Leverenz, J.B., Levey, A.I., Li, G., Lieberman, A.P., Lunetta, K.L., Lyketsos, C.G., Marson, D.C., Martiniuk, F., Mash, D.C., Masliah, E., McCormick, W.C., McCurry, S.M., McDavid, A.N., McKee, A.C., Mesulam, M., Miller, B.L., Miller, C.A., Miller, J.W., Morris, J.C., Murrell, J.R., Myers, A.J., O'Bryant, S., Olichney, J.M., Pankratz, V.S., Parisi, J.E., Paulson, H.L., Perry, W., Peskind, E., Pierce, A., Poon, W.W., Potter, H., Quinn, J.F., Raj, A., Raskind, M., Reisberg, B., Reitz, C., Ringman, J.M., Roberson, E.D., Rogaeva, E., Rosen, H.J., Rosenberg, R.N., Sager, M.A., Saykin, A.J., Schneider, J.A., Schneider, L.S., Seeley, W.W., Smith, A.G., Sonnen, J.A., Spina, S., Stern, R.A., Swerdlow, R.H., Tanzi, R.E., Thornton-Wells, T.A., Trojanowski, J.Q., Troncoso, J.C., Van Deerlin, V.M., Van Eldik, L.J., Vinters, H.V., Vonsattel, J.P., Weintraub, S., Welsh-Bohmer, K.A., Wilhelmsen, K.C., Williamson, J., Wingo, T.S., Woltjer, R.L., Wright, C.B., Yu, C.E., Yu, L., Garzia, F., Golamaully, F., Septier, G., Engelborghs, S., Vandenberghe, R., De Deyn, P.P., Fernadez, C.M., Benito, Y.A., Thonberg, H., Forsell, C., Lilius, L., Kinhult-Stählbom, A., Kilander, L., Brundin, R., Concari, L., Helisalmi, S., Koivisto, A.M., Haapasalo, A., Dermecourt, V., Fievet, N., Hanon, O., Dufouil, C., Brice, A., Ritchie, K., Dubois, B., Himali, J.J., Keene, C.D., Tschanz, J., Fitzpatrick, A.L., Kukull, W.A., Norton, M., Aspelund, T., Larson, E.B., Munger, R., Rotter, J.I., Lipton, R.B., Bullido, M.J., Hofman, A., Montine, T.J., Coto, E., Boerwinkle, E., Petersen, R.C., Alvarez, V., Rivadeneira, F., Reiman, E.M., Gallo, M., O'Donnell, C.J., Reisch, J.S., Bruni, A.C., Royall, D.R., Dichgans, M., Sano, M., Galimberti, D., St George-Hyslop, P., Scarpini, E., Tsuang, D.W., Mancuso, M., Bonuccelli, U., Winslow, A.R., Daniele, A., Wu, C.K., Peters, O., Nacmias, B., Riemenschneider, M., Heun, R., Brayne, C., Rubinsztein, D.C., Bras, J., Guerreiro, R., Al-Chalabi, A., Shaw, C.E., Collinge, J., Mann, D., Tsolaki, M., Clarimón, J., Sussams, R., Lovestone, S., O'Donovan, M.C., Owen, M.J., Behrens, T.W., Mead, S., Goate, A.M., Uitterlinden, A.G., Holmes, C., Cruchaga, C., Ingelsson, M., Bennett, D.A., Powell, J., Golde, T.E., Graff, C., De Jager, P.L., Morgan, K., Ertekin-Taner, N., Combarros, O., Psaty, B.M., Passmore, P., Younkin, S.G., Berr, C., Gudnason, V., Rujescu, D., Dickson, D.W., Dartigues, J.F., DeStefano, A.L., Ortega-Cubero, S., Hakonarson, H., Campion, D., Boada, M., Kauwe, J.K., Farrer, L.A., Van Broeckhoven, C., Ikram, M.A., Jones, L., Haines, J.L., Tzourio, C., Launer, L.J., Escott-Price, V., Mayeux, R., Deleuze, J.F., Amin, N., Holmans, P.A., Pericak-Vance, M.A., Amouyel, P., van Duijn, C.M., Ramirez, A., Wang, L.S., Lambert, J.C., Seshadri, S., Williams, J., Schellenberg, G.D., Peloso, Gina M., van der Lee, Sven J., Destefano, Anita L., and Seshardi, Sudha

Published
2018
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4. Analysis of shared heritability in common disorders of the brain

Author

Anttila, V. Bulik-Sullivan, B. Finucane, H.K. Walters, R.K. Bras, J. Duncan, L. Escott-Price, V. Falcone, G.J. Gormley, P. Malik, R. Patsopoulos, N.A. Ripke, S. Wei, Z. Yu, D. Lee, P.H. Turley, P. Grenier-Boley, B. Chouraki, V. Kamatani, Y. Berr, C. Letenneur, L. Hannequin, D. Amouyel, P. Boland, A. Deleuze, J.-F. Duron, E. Vardarajan, B.N. Reitz, C. Goate, A.M. Huentelman, M.J. Ilyas Kamboh, M. Larson, E.B. Rogaeva, E. George-Hyslop, P.S. Hakonarson, H. Kukull, W.A. Farrer, L.A. Barnes, L.L. Beach, T.G. Yesim Demirci, F. Head, E. Hulette, C.M. Jicha, G.A. Kauwe, J.S.K. Kaye, J.A. Leverenz, J.B. Levey, A.I. Lieberman, A.P. Pankratz, V.S. Poon, W.W. Quinn, J.F. Saykin, A.J. Schneider, L.S. Smith, A.G. Sonnen, J.A. Stern, R.A. Van Deerlin, V.M. Van Eldik, L.J. Harold, D. Russo, G. Rubinsztein, D.C. Bayer, A. Tsolaki, M. Proitsi, P. Fox, N.C. Hampel, H. Owen, M.J. Mead, S. Passmore, P. Morgan, K. Nöthen, M.M. Rossor, M. Lupton, M.K. Hoffmann, P. Kornhuber, J. Lawlor, B. McQuillin, A. Al-Chalabi, A. Bis, J.C. Ruiz, A. Boada, M. Seshadri, S. Beiser, A. Rice, K. Van Der Lee, S.J. De Jager, P.L. Geschwind, D.H. Riemenschneider, M. Riedel-Heller, S. Rotter, J.I. Ransmayr, G. Hyman, B.T. Cruchaga, C. Alegret, M. Winsvold, B. Palta, P. Farh, K.-H. Cuenca-Leon, E. Furlotte, N. Kurth, T. Ligthart, L. Terwindt, G.M. Freilinger, T. Ran, C. Gordon, S.D. Borck, G. Adams, H.H.H. Lehtimäki, T. Wedenoja, J. Buring, J.E. Schürks, M. Hrafnsdottir, M. Hottenga, J.-J. Penninx, B. Artto, V. Kaunisto, M. Vepsäläinen, S. Martin, N.G. Montgomery, G.W. Kurki, M.I. Hämäläinen, E. Huang, H. Huang, J. Sandor, C. Webber, C. Muller-Myhsok, B. Schreiber, S. Salomaa, V. Loehrer, E. Göbel, H. Macaya, A. Pozo-Rosich, P. Hansen, T. Werge, T. Kaprio, J. Metspalu, A. Kubisch, C. Ferrari, M.D. Belin, A.C. Van Den Maagdenberg, A.M.J.M. Zwart, J.-A. Boomsma, D. Eriksson, N. Olesen, J. Chasman, D.I. Nyholt, D.R. Avbersek, A. Baum, L. Berkovic, S. Bradfield, J. Buono, R. Catarino, C.B. Cossette, P. De Jonghe, P. Depondt, C. Dlugos, D. Ferraro, T.N. French, J. Hjalgrim, H. Jamnadas-Khoda, J. Kälviäinen, R. Kunz, W.S. Lerche, H. Leu, C. Lindhout, D. Lo, W. Lowenstein, D. McCormack, M. Møller, R.S. Molloy, A. Ng, P.-W. Oliver, K. Privitera, M. Radtke, R. Ruppert, A.-K. Sander, T. Schachter, S. Schankin, C. Scheffer, I. Schoch, S. Sisodiya, S.M. Smith, P. Sperling, M. Striano, P. Surges, R. Neil Thomas, G. Visscher, F. Whelan, C.D. Zara, F. Heinzen, E.L. Marson, A. Becker, F. Stroink, H. Zimprich, F. Gasser, T. Gibbs, R. Heutink, P. Martinez, M. Morris, H.R. Sharma, M. Ryten, M. Mok, K.Y. Pulit, S. Bevan, S. Holliday, E. Attia, J. Battey, T. Boncoraglio, G. Thijs, V. Chen, W.-M. Mitchell, B. Rothwell, P. Sharma, P. Sudlow, C. Vicente, A. Markus, H. Kourkoulis, C. Pera, J. Raffeld, M. Silliman, S. Perica, V.B. Thornton, L.M. Huckins, L.M. William Rayner, N. Lewis, C.M. Gratacos, M. Rybakowski, F. Keski-Rahkonen, A. Raevuori, A. Hudson, J.I. Reichborn-Kjennerud, T. Monteleone, P. Karwautz, A. Mannik, K. Baker, J.H. O'Toole, J.K. Trace, S.E. Davis, O.S.P. Helder, S.G. Ehrlich, S. Herpertz-Dahlmann, B. Danner, U.N. Van Elburg, A.A. Clementi, M. Forzan, M. Docampo, E. Lissowska, J. Hauser, J. Tortorella, A. Maj, M. Gonidakis, F. Tziouvas, K. Papezova, H. Yilmaz, Z. Wagner, G. Cohen-Woods, S. Herms, S. Julia, A. Rabionet, R. Dick, D.M. Ripatti, S. Andreassen, O.A. Espeseth, T. Lundervold, A.J. Steen, V.M. Pinto, D. Scherer, S.W. Aschauer, H. Schosser, A. Alfredsson, L. Padyukov, L. Halmi, K.A. Mitchell, J. Strober, M. Bergen, A.W. Kaye, W. Szatkiewicz, J.P. Cormand, B. Ramos-Quiroga, J.A. Sánchez-Mora, C. Ribasés, M. Casas, M. Hervas, A. Arranz, M.J. Haavik, J. Zayats, T. Johansson, S. Williams, N. Dempfle, A. Rothenberger, A. Kuntsi, J. Oades, R.D. Banaschewski, T. Franke, B. Buitelaar, J.K. Vasquez, A.A. Doyle, A.E. Reif, A. Lesch, K.-P. Freitag, C. Rivero, O. Palmason, H. Romanos, M. Langley, K. Rietschel, M. Witt, S.H. Dalsgaard, S. Børglum, A.D. Waldman, I. Wilmot, B. Molly, N. Bau, C.H.D. Crosbie, J. Schachar, R. Loo, S.K. McGough, J.J. Grevet, E.H. Medland, S.E. Robinson, E. Weiss, L.A. Bacchelli, E. Bailey, A. Bal, V. Battaglia, A. Betancur, C. Bolton, P. Cantor, R. Celestino-Soper, P. Dawson, G. De Rubeis, S. Duque, F. Green, A. Klauck, S.M. Leboyer, M. Levitt, P. Maestrini, E. Mane, S. Moreno-De-Luca, D. Parr, J. Regan, R. Reichenberg, A. Sandin, S. Vorstman, J. Wassink, T. Wijsman, E. Cook, E. Santangelo, S. Delorme, R. Roge, B. Magalhaes, T. Arking, D. Schulze, T.G. Thompson, R.C. Strohmaier, J. Matthews, K. Melle, I. Morris, D. Blackwood, D. McIntosh, A. Bergen, S.E. Schalling, M. Jamain, S. Maaser, A. Fischer, S.B. Reinbold, C.S. Fullerton, J.M. Guzman-Parra, J. Mayoral, F. Schofield, P.R. Cichon, S. Mühleisen, T.W. Degenhardt, F. Schumacher, J. Bauer, M. Mitchell, P.B. Gershon, E.S. Rice, J. Potash, J.B. Zandi, P.P. Craddock, N. Nicol Ferrier, I. Alda, M. Rouleau, G.A. Turecki, G. Ophoff, R. Pato, C. Anjorin, A. Stahl, E. Leber, M. Czerski, P.M. Cruceanu, C. Jones, I.R. Posthuma, D. Andlauer, T.F.M. Forstner, A.J. Streit, F. Baune, B.T. Air, T. Sinnamon, G. Wray, N.R. MacIntyre, D.J. Porteous, D. Homuth, G. Rivera, M. Grove, J. Middeldorp, C.M. Hickie, I. Pergadia, M. Mehta, D. Smit, J.H. Jansen, R. De Geus, E. Dunn, E. Li, Q.S. Nauck, M. Schoevers, R.A. Beekman, A.T.F. Knowles, J.A. Viktorin, A. Arnold, P. Barr, C.L. Bedoya-Berrio, G. Joseph Bienvenu, O. Brentani, H. Burton, C. Camarena, B. Cappi, C. Cath, D. Cavallini, M. Cusi, D. Darrow, S. Denys, D. Derks, E.M. Dietrich, A. Fernandez, T. Figee, M. Freimer, N. Gerber, G. Grados, M. Greenberg, E. Hanna, G.L. Hartmann, A. Hirschtritt, M.E. Hoekstra, P.J. Huang, A. Huyser, C. Illmann, C. Jenike, M. Kuperman, S. Leventhal, B. Lochner, C. Lyon, G.J. Macciardi, F. Madruga-Garrido, M. Malaty, I.A. Maras, A. McGrath, L. Miguel, E.C. Mir, P. Nestadt, G. Nicolini, H. Okun, M.S. Pakstis, A. Paschou, P. Piacentini, J. Pittenger, C. Plessen, K. Ramensky, V. Ramos, E.M. Reus, V. Richter, M.A. Riddle, M.A. Robertson, M.M. Roessner, V. Rosário, M. Samuels, J.F. Sandor, P. Stein, D.J. Tsetsos, F. Van Nieuwerburgh, F. Weatherall, S. Wendland, J.R. Wolanczyk, T. Worbe, Y. Zai, G. Goes, F.S. McLaughlin, N. Nestadt, P.S. Grabe, H.-J. Depienne, C. Konkashbaev, A. Lanzagorta, N. Valencia-Duarte, A. Bramon, E. Buccola, N. Cahn, W. Cairns, M. Chong, S.A. Cohen, D. Crespo-Facorro, B. Crowley, J. Davidson, M. DeLisi, L. Dinan, T. Donohoe, G. Drapeau, E. Duan, J. Haan, L. Hougaard, D. Karachanak-Yankova, S. Khrunin, A. Klovins, J. Kučinskas, V. Keong, J.L.C. Limborska, S. Loughland, C. Lönnqvist, J. Maher, B. Mattheisen, M. McDonald, C. Murphy, K.C. Nenadic, I. Van Os, J. Pantelis, C. Pato, M. Petryshen, T. Quested, D. Roussos, P. Sanders, A.R. Schall, U. Schwab, S.G. Sim, K. So, H.-C. Stögmann, E. Subramaniam, M. Toncheva, D. Waddington, J. Walters, J. Weiser, M. Cheng, W. Cloninger, R. Curtis, D. Gejman, P.V. Henskens, F. Mattingsdal, M. Oh, S.-Y. Scott, R. Webb, B. Breen, G. Churchhouse, C. Bulik, C.M. Daly, M. Dichgans, M. Faraone, S.V. Guerreiro, R. Holmans, P. Kendler, K.S. Koeleman, B. Mathews, C.A. Price, A. Scharf, J. Sklar, P. Williams, J. Wood, N.W. Cotsapas, C. Palotie, A. Smoller, J.W. Sullivan, P. Rosand, J. Corvin, A. Neale, B.M. The Brainstorm Consortium

Abstract

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American Association for the Advancement of Science. All rights reserved.

Published
2018

5. Analysis of shared heritability in common disorders of the brain

Author

Anttila, V., Bulik-Sullivan, B., Finucane, H.K., Walters, R.K., Bras, J., Duncan, L., Escott-Price, V., Falcone, G.J., Gormley, P., Malik, R., Patsopoulos, N.A., Ripke, S., Wei, Z., Yu, D., Lee, P.H., Turley, P., Grenier-Boley, B., Chouraki, V., Kamatani, Y., Berr, C., Letenneur, L., Hannequin, D., Amouyel, P., Boland, A., Deleuze, J.F., Duron, E., Vardarajan, B.N., Reitz, C., Goate, A.M., Huentelman, M.J., Kamboh, M.I., Larson, E.B., Rogaeva, E., George-Hyslop, P. St, Hakonarson, H., Kukull, W.A., Farrer, L.A., Barnes, L.L., Beach, T.G., Demirci, F.Y., Head, E., Hulette, C.M., Jicha, G.A., Kauwe, J.S.K., Kaye, J.A., Leverenz, J.B., Levey, A.I., Lieberman, A.P., Pankratz, V.S., Poon, W.W., Quinn, J.F., Saykin, A.J., Schneider, L.S., Smith, A.G., Sonnen, J.A., Stern, R.A., Deerlin, V.M. Van, Eldik, L.J. Van, Harold, D., Russo, G., Rubinsztein, D.C., Bayer, A., Tsolaki, M., Proitsi, P., Fox, N.C., Hampel, H., Owen, M.J., Mead, S., Passmore, P., Morgan, K., Nothen, M.M., Rossor, M., Lupton, M.K., Hoffmann, P., Kornhuber, J., Lawlor, B., McQuillin, A., Al-Chalabi, A., Bis, J.C., Ruiz, A., Boada, M., Seshadri, S., Beiser, A., Rice, K., Lee, S.J. van der, Jager, P.L. De, Geschwind, D.H., Riemenschneider, M., Riedel-Heller, S., Rotter, J.I., Ransmayr, G., Hyman, B.T., Cruchaga, C., Alegret, M., Winsvold, B., Palta, P., Farh, K.H., Cuenca-Leon, E., Furlotte, N., Kurth, T., et al., Stroink, H., Franke, B., Buitelaar, J.K., Arias Vasquez, A., Corvin, A., and Neale, B.M.

Subjects
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Abstract

Contains fulltext : 193271pub.pdf (Publisher’s version ) (Open Access) Contains fulltext : 193271pre.pdf (Author’s version preprint ) (Open Access) Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. 13 p.

Published
2018
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6. Analysis of shared heritability in common disorders of the brain

Author

Anttila, V. Bulik-Sullivan, B. Finucane, H.K. Walters, R.K. Bras, J. Duncan, L. Escott-Price, V. Falcone, G.J. Gormley, P. Malik, R. Patsopoulos, N.A. Ripke, S. Wei, Z. Yu, D. Lee, P.H. Turley, P. Grenier-Boley, B. Chouraki, V. Kamatani, Y. Berr, C. Letenneur, L. Hannequin, D. Amouyel, P. Boland, A. Deleuze, J.-F. Duron, E. Vardarajan, B.N. Reitz, C. Goate, A.M. Huentelman, M.J. Ilyas Kamboh, M. Larson, E.B. Rogaeva, E. George-Hyslop, P.S. Hakonarson, H. Kukull, W.A. Farrer, L.A. Barnes, L.L. Beach, T.G. Yesim Demirci, F. Head, E. Hulette, C.M. Jicha, G.A. Kauwe, J.S.K. Kaye, J.A. Leverenz, J.B. Levey, A.I. Lieberman, A.P. Pankratz, V.S. Poon, W.W. Quinn, J.F. Saykin, A.J. Schneider, L.S. Smith, A.G. Sonnen, J.A. Stern, R.A. Van Deerlin, V.M. Van Eldik, L.J. Harold, D. Russo, G. Rubinsztein, D.C. Bayer, A. Tsolaki, M. Proitsi, P. Fox, N.C. Hampel, H. Owen, M.J. Mead, S. Passmore, P. Morgan, K. Nöthen, M.M. Rossor, M. Lupton, M.K. Hoffmann, P. Kornhuber, J. Lawlor, B. McQuillin, A. Al-Chalabi, A. Bis, J.C. Ruiz, A. Boada, M. Seshadri, S. Beiser, A. Rice, K. Van Der Lee, S.J. De Jager, P.L. Geschwind, D.H. Riemenschneider, M. Riedel-Heller, S. Rotter, J.I. Ransmayr, G. Hyman, B.T. Cruchaga, C. Alegret, M. Winsvold, B. Palta, P. Farh, K.-H. Cuenca-Leon, E. Furlotte, N. Kurth, T. Ligthart, L. Terwindt, G.M. Freilinger, T. Ran, C. Gordon, S.D. Borck, G. Adams, H.H.H. Lehtimäki, T. Wedenoja, J. Buring, J.E. Schürks, M. Hrafnsdottir, M. Hottenga, J.-J. Penninx, B. Artto, V. Kaunisto, M. Vepsäläinen, S. Martin, N.G. Montgomery, G.W. Kurki, M.I. Hämäläinen, E. Huang, H. Huang, J. Sandor, C. Webber, C. Muller-Myhsok, B. Schreiber, S. Salomaa, V. Loehrer, E. Göbel, H. Macaya, A. Pozo-Rosich, P. Hansen, T. Werge, T. Kaprio, J. Metspalu, A. Kubisch, C. Ferrari, M.D. Belin, A.C. Van Den Maagdenberg, A.M.J.M. Zwart, J.-A. Boomsma, D. Eriksson, N. Olesen, J. Chasman, D.I. Nyholt, D.R. Avbersek, A. Baum, L. Berkovic, S. Bradfield, J. Buono, R. Catarino, C.B. Cossette, P. De Jonghe and Anttila, V. Bulik-Sullivan, B. Finucane, H.K. Walters, R.K. Bras, J. Duncan, L. Escott-Price, V. Falcone, G.J. Gormley, P. Malik, R. Patsopoulos, N.A. Ripke, S. Wei, Z. Yu, D. Lee, P.H. Turley, P. Grenier-Boley, B. Chouraki, V. Kamatani, Y. Berr, C. Letenneur, L. Hannequin, D. Amouyel, P. Boland, A. Deleuze, J.-F. Duron, E. Vardarajan, B.N. Reitz, C. Goate, A.M. Huentelman, M.J. Ilyas Kamboh, M. Larson, E.B. Rogaeva, E. George-Hyslop, P.S. Hakonarson, H. Kukull, W.A. Farrer, L.A. Barnes, L.L. Beach, T.G. Yesim Demirci, F. Head, E. Hulette, C.M. Jicha, G.A. Kauwe, J.S.K. Kaye, J.A. Leverenz, J.B. Levey, A.I. Lieberman, A.P. Pankratz, V.S. Poon, W.W. Quinn, J.F. Saykin, A.J. Schneider, L.S. Smith, A.G. Sonnen, J.A. Stern, R.A. Van Deerlin, V.M. Van Eldik, L.J. Harold, D. Russo, G. Rubinsztein, D.C. Bayer, A. Tsolaki, M. Proitsi, P. Fox, N.C. Hampel, H. Owen, M.J. Mead, S. Passmore, P. Morgan, K. Nöthen, M.M. Rossor, M. Lupton, M.K. Hoffmann, P. Kornhuber, J. Lawlor, B. McQuillin, A. Al-Chalabi, A. Bis, J.C. Ruiz, A. Boada, M. Seshadri, S. Beiser, A. Rice, K. Van Der Lee, S.J. De Jager, P.L. Geschwind, D.H. Riemenschneider, M. Riedel-Heller, S. Rotter, J.I. Ransmayr, G. Hyman, B.T. Cruchaga, C. Alegret, M. Winsvold, B. Palta, P. Farh, K.-H. Cuenca-Leon, E. Furlotte, N. Kurth, T. Ligthart, L. Terwindt, G.M. Freilinger, T. Ran, C. Gordon, S.D. Borck, G. Adams, H.H.H. Lehtimäki, T. Wedenoja, J. Buring, J.E. Schürks, M. Hrafnsdottir, M. Hottenga, J.-J. Penninx, B. Artto, V. Kaunisto, M. Vepsäläinen, S. Martin, N.G. Montgomery, G.W. Kurki, M.I. Hämäläinen, E. Huang, H. Huang, J. Sandor, C. Webber, C. Muller-Myhsok, B. Schreiber, S. Salomaa, V. Loehrer, E. Göbel, H. Macaya, A. Pozo-Rosich, P. Hansen, T. Werge, T. Kaprio, J. Metspalu, A. Kubisch, C. Ferrari, M.D. Belin, A.C. Van Den Maagdenberg, A.M.J.M. Zwart, J.-A. Boomsma, D. Eriksson, N. Olesen, J. Chasman, D.I. Nyholt, D.R. Avbersek, A. Baum, L. Berkovic, S. Bradfield, J. Buono, R. Catarino, C.B. Cossette, P. De Jonghe

Abstract

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American Association for the Advancement of Science. All rights reserved.

Published
2018

7. Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Author

Peloso, G.M. (Gina M.), Lee, S.J. (Sven) van der, Sims, R. (Rebecca), van der Lee, S.J. (S. J.), Naj, A.C. (A. C.), Bellenguez, C. (Céline), Badarinarayan, N. (Nandini), Jakobsdottir, M. (Margret), Kunkle, B.W. (B. W.), Boland, A. (A.), Raybould, R. (R.), Bis, J.C. (Joshua), Martin, E.R. (E. R.), Grenier-Boley, B. (Benjamin), Heilmann-Heimbach, S. (S.), Chouraki, V. (V.), Kuzma, A.B. (A. B.), Sleegers, K. (K.), Vronskaya, M., Ruiz, A. (A.), Graham, R.R. (Robert), Olaso, R. (Robert), Hoffmann, P. (Per), Grove, M.L. (Megan), Vardarajan, B.N. (Badri), Hiltunen, M. (Mikko), Nöthen, M.M. (Markus), White, C.C. (Charles), Hamilton-Nelson, K.L. (K. L.), Epelbaum, J. (Jacques), Maier, W. (Wolfgang), Choi, S.H. (S. H.), Beecham, G.W., Dulary, C. (C.), Herms, S. (Stefan), Smith, A.V. (Albert), Funk, C.C. (C. C.), Derbois, (), Forstner, A.J. (Andreas), Ahmad, S. (S.), Li, H. (Huaixing), Bacq, D. (D.), Harold, D. (D.), Satizabal, C.L. (Claudia), Valladares, O. (Otto), Squassini, A. (Alessio), Thomas, R. (R.), Brody, J.A. (Jennifer A.), Qu, L. (Liming), Sanchez-Juan, P. (Pascual), Morgan, T. (Thomas), Wolters, F.J. (Frank), Zhao, Y. (Y.), Garcia, F.S. (F. S.), Denning, N. (Nicola), Fornage, M. (Myriam), Malamon, J. (J.), Naranjo, M.C.D. (M. C.D.), Majounie, E. (Elisa), Mosley, T.H. (Thomas H.), Dombroski, B. (B.), Wallon, D. (David), Lupton, M.K. (Michelle), Dupuis, J. (Josée), Whitehead, P. (P.), Fratiglioni, L. (L.), Medway, C. (Christopher), Jian, X. (X.), Mukherjee, S. (S.), Keller, L. (L.), Brown, K. (Kristelle), Lin, H. (Honghuang), Cantwell, L.B. (Laura B.), Panza, F. (F.), McGuinness, B. (B.), Moreno-Grau, S. (S.), Burgess, J.D. (J. D.), Solfrizzi, V. (Vincenzo), Proitsi, P. (P.), Adams, H.H.H. (Hieab), Allen, M. (M.), Seripa, D. (Davide), Pastor, P. (P.), Cupples, L.A. (L. A.), Price, N.D. (N. D.), Hannequin, D. (Didier), Frank-Garcia, A. (Ana), Levy, D. (D.), Chakrabarty, P. (P.), Caffarra, P. (Paolo), Giegling, I. (Ina), Beiser, A. (Alexa), Giedraitis, V. (Vilmantas), Hampel, H. (Heather), Garcia, M.E. (M.), Wang, X. (X.), Lannfelt, L. (Lars), Mecocci, P. (Patrizia), Eiriksdottir, G. (Gudny), Crane, L.M.A., Pasquier, F. (Florence), Boccardi, V. (V.), Henández, I. (I.), Barber, R.C. (R. C.), Scherer, M. (M.), Tárraga, L. (L.), Adams, P.M. (P. M.), Leber, I. (Isabelle), Chen, Y.D.I. (Yii-Der Ida), Albert, M. (Michael), Riedel-Heller, S. (Steffi), Emilsson, V. (Valur), Beekly, D. (D.), Braae, A. (A.), Schmidt, R. (R.), Blacker, D. (D.), Masullo, C., Schmidt, H. (Helena), Doody, R.S. (R. S.), Spalletta, G. (Gianfranco), Longstreth Jr, W.T., Fairchild, T.J. (T. J.), Bossù, P. (P.), Lopez, O.L. (Oscar), Frosch, M.P. (Matthew), Sacchinelli, E. (E.), Ghetti, B. (Bernardino), Yang, Q. (Qiong Fang), Huebinger, R.M. (R. M.), Jessen, F., Li, S. (S.), Kamboh, M.I. (M. I.), Morris, J. (J.), Sotolongo-Grau, O. (O.), Katz, M.J. (M. J.), Corcoran, C. (C.), Dunstan, M.L., Braddel, A. (A.), Thomas, C. (C.), Meggy, A. (A.), Marshall, R. (R.), Gerrish, A. (Amy), Chapman, J. (Jade), Aguilar, M. (M.), Taylor, S. (S.), Hill, M. (M.), Fairén, M.D. (M. D.), Hodges, A. (A.), Vellas, B. (B.), Soininen, H. (H.), Kloszewska, I. (Iwona), Daniilidou, M. (M.), Uphill, J. (James), Patel, Y. (Y.), Hughes, J.T. (J. T.), Lord, J. (J.), Turton, J.C. (James), Hartmann, A.M. (A. M.), Cecchetti, R. (R.), Fenoglio, C. (Chiara), Serpente, M. (Maria), Arcaro, M. (M.), Caltagirone, C. (C.), Orfei, M.D. (M. D.), Ciaramella, A. (A.), Pichler, I. (Irene), Mayhaus, M. (Manuel), Gu, W. (W.), Lleo, A. (Alberto), Fortea, J. (J.), Blesa, R. (Rafael), Barber, I.S. (I. S.), Brookes, K. (K.), Cupidi, C. (Chiara), Maletta, R. (Raffaele), Carrell, D. (D.), Sorbi, S. (Sandro), Moebus, S. (Susanne), Urbano, M. (M.), Pilotto, A. (Alberto), Kornhuber, J. (Johannes), Bosco, P. (Paolo), Todd, S. (S.), Craig, D. (D.), Johnston, J. (J.), Gill, M. (M.), Lawlor, B.A. (B.), Lynch, A. (Aoibhinn), Fox, N.C. (Nick), Hardy, J. (J.), Albin, R.L. (R. L.), Apostolova, L.G. (L. G.), Arnold, S.E. (Steven), Asthana, S. (S.), Atwood, C.S. (Craig), Baldwin, C. (Clinton), Barnes, L.L. (L. L.), Barral, S. (Sandra), Beach, T.G. (Thomas), Becker, J.T. (James), Bigio, E.H. (Eileen), Bird, T.D. (T. D.), Boeve, B.F. (Bradley), Bowen, J.D. (J. D.), Boxer, A.L. (Adam), Burke, J.R. (J. R.), Burns, J.M. (J. M.), Buxbaum, J.D. (J. D.), Cairns, N.J. (N. J.), Cao, C. (C.), Carlson, C. (Chris), Carlsson, C.M. (C. M.), Carney, R.M. (R. M.), Carrasquillo, M.M. (M. M.), Carroll, S.L. (Steven), Diaz, C.C. (C. C.), Chui, H.C. (H. C.), Clark, D.G. (D. G.), Cribbs, D.H. (D. H.), Crocco, E.A. (E. A.), DeCarli, C. (Charles), Dick, M. (M.), Duara, R. (R.), Evans, D.A. (D. A.), Faber, K.M. (Kelley), Fallon, K.B. (K. B.), Fardo, D.W. (D. W.), Farlow, M.R. (M. R.), Ferris, S. (S.), Foroud, T.M. (T. M.), Galasko, D.R. (D. R.), Gearing, M. (Marla), Geschwind, H., Gilbert, J.R. (John R.), Graff-Radford, N.R. (Neill), Green, R.C. (Robert), Growdon, J.H. (J. H.), Hamilton, R.L. (Ronald L.), Harrell, L.E. (L. E.), Honig, L.S. (L. S.), Huentelman, M.J. (M. J.), Hulette, C. (Christine), Hyman, B.T. (Bradley), Jarvik, G.P. (Gail), Abner, E. (E.), Jin, L.W. (L. W.), Jun, G. (G.), Karydas, A. (A.), Kaye, J.A. (Jeffrey), Kim, R. (R.), Kowall, N.W. (N. W.), Kramer, J.H. (Joel), LaFerla, F.M. (F. M.), Lah, J.J. (J. J.), Leverenz, J.B. (J. B.), Levey, A.I. (Allan), Li, G. (Guo), Lieberman, A.P. (A. P.), Lunetta, K.L. (Kathryn), Lyketsos, C.G. (C. G.), Marson, D.C. (D. C.), Martiniuk, F. (F.), Mash, D.C. (Deborah C.), Masliah, E. (Eliezer), McCormick, W.C. (W. C.), McCurry, S.M. (S. M.), McDavid, A.N. (A. N.), McKee, A.C. (A. C.), Mesulam, M. (Marsel), Miller, B.L. (Bruce Lars), Miller, C.A. (C. A.), Miller, J.W. (J. W.), Morris, H. (Huw), Myers, A.J. (Amanda J.), O'Bryant, S. (S.), Olichney, J.M. (J. M.), Pankratz, V.S. (Shane), Parisi, J.E. (Joseph), Paulson, H.L. (Henry), Perry, W. (W.), Peskind, E. (E.), Pierce, A. (A.), Poon, W.W. (W. W.), Potter, H. (H.), Quinn, J.F. (J. F.), Raj, A. (A.), Raskind, M. (M.), Reisberg, B. (B.), Reitz, C. (C.), Ringman, J.M. (J. M.), Roberson, E.D. (E. D.), Rogaeva, E. (Ekaterina), Rosen, H.J. (H. J.), Rosenberg, R.N. (Roger), Sager, M.A. (M. A.), Saykin, A.J. (Andrew), Schneider, J.A. (Julie), Schneider, L.S. (L. S.), Seeley, W.W. (W. W.), Smith, A.G. (A. G.), Sonnen, J.A. (J. A.), Spina, S. (S.), Stern, R.A. (R. A.), Swerdlow, R.H. (R. H.), Tanzi, R.E. (R. E.), Thornton-Wells, T.A. (Tricia), Trojanowski, J.Q. (J. Q.), Troncoso, J.C. (J. C.), Deerlin, V.M. (Vivianna), Van Eldik, L.J. (L. J.), Vinters, H.V. (Harry), Vonsattel, J.P. (Jean Paul), Weintraub, S. (Sandra), Welsh-Bohmer, K.A. (Kathleen), Wilhelmsen, K.C., Williamson, J. (J.), Wingo, T.S. (T. S.), Woltjer, R.L. (Randall), Wright, C.B. (Clinton B.), Yu, C.E. (C. E.), Yu, L. (L.), Garzia, F. (F.), Golamaully, F. (F.), Septier, G. (G.), Engelborghs, S. (Sebastiaan), Vandenberghe, R. (Rik), Deyn, P.P. (Peter) de, Fernadez, C.M. (C. M.), Benito, Y.A. (Y. A.), Thonberg, H. (Håkan), Forsell, C. (C.), Lilius, L. (Lena), Kinhult-Stählbom, A. (A.), Kilander, L. (L.), Brundin, R. (R.), Concari, L. (L.), Helisalmi, S. (S.), Koivisto, A.M. (A. M.), Haapasalo, A. (Annakaisa), Dermecourt, V. (V.), Fievet, N. (N.), Hanon, O. (Olivier), Dufouil, C. (Carole), Brice, A., Ritchie, K. (Karen), Dubois, B. (B.), Himali, J.J. (Jayandra), Keene, C.D. (C. D.), Tschanz, J. (J.), Fitzpatrick, A.L. (Annette), Kukull, W.A., Norton, M. (M.), Aspelund, T. (Thor), Larson, E.B. (Eric B.), Munger, R. (R.), Rotter, J.I. (Jerome I.), Lipton, R.B. (R. B.), Bullido, M.J. (Maria), Hofman, A. (A.), Montine, T.J. (T. J.), Coto, E. (Eliecer), Boerwinkle, E. (E.), Petersen, R.C. (R. C.), Alvarez, V. (V.), Rivadeneira Ramirez, F. (Fernando), Reiman, E.M. (Eric), Gallo, V. (Valentina), O'Donnell, C.J. (Christopher), Reisch, J.S. (J. S.), Bruni, A.C. (Amalia), Royall, D.R. (D. R.), Kubisch, C. (Christian), Sano, M. (M.), Galimberti, D. (Daniela), St. George-Hyslop, P. (Peter), Scarpini, E. (Elio), Tsuang, D.W. (Debby W.), Mancuso, M. (M.), Bonuccelli, U. (Ubaldo), Winslow, A.R. (A. R.), Daniele, A. (A.), Wu, C.K. (C. K.), Peters, O. (Oscar), Nacmias, B. (Benedetta), Riemenschneider, M. (M.), Heun, R. (Reinhard), Brayne, C. (Carol), Rubinsztein, D.C. (David), Bras, J. (J.), Guerreiro, R. (R.), Al-Chalabi, A. (Ammar), Shaw, C.E. (C. E.), Collinge, J. (J.), Mann, D. (D.), Tsolaki, M. (Magda), Clarimón, J. (J.), Sussams, R. (R.), Lovestone, S. (Simon), O'donovan, M.C. (Michael), Owen, M.J. (Michael), Behrens, T.W. (Timothy), Mead, S. (S.), Goate, A.M. (Alison), Uitterlinden, A.G. (A. G.), Holmes, C. (C.), Cruchaga, C. (Carlos), Ingelsson, M. (Martin), Bennett, D.A. (David), Powell, J. (J.), Golde, T.E. (T. E.), Graff, C. (C.), De Jager, P., Morgan, K. (Kevin), Ertekin-Taner, N. (N.), Combarros, O. (Onofre), Psaty, B.M. (Bruce), Passmore, P. (P.), Younkin, S.G. (S. G.), Berr, C. (Claudine), Gudnason, V. (Vilmundur), Rujescu, D. (D.), Dickson, D. (Dennis), Dartigues, J.-F., DeStefano, A.L. (Anita), Ortega-Cubero, S. (S.), Hakonarson, H. (Hakon), Campion, D. (Dominique), Boada, M. (M.), Kauwe, J.K. (J. K.), Farrer, L.A. (Lindsay), Broeckhoven, C. (Christine) van, Ikram, M.A. (Arfan), Jones, L. (L.), Haines, J.L. (Jonathan), Tzourio, C. (Christophe), Launer, L.J. (Lenore), Escott-Price, V. (V.), Mayeux, R. (R.), Deleuze, J.-F. (Jean-François), Amin, N. (Najaf), Holmans, P.A. (Peter A.), Kunkle, B. (Brian), Amouyel, P. (Philippe), Duijn, C.M. (Cornelia) van, Ramirez, A. (Alfredo), Wang, L.S. (L. S.), Lambert, J.-C. (J.), Seshadri, S. (Sudha), Williams, J. (J.), Schellenberg, G.D. (Gerard), Destefano, A.L. (Anita L.), Seshardi, S. (Sudha), Peloso, G.M. (Gina M.), Lee, S.J. (Sven) van der, Sims, R. (Rebecca), van der Lee, S.J. (S. J.), Naj, A.C. (A. C.), Bellenguez, C. (Céline), Badarinarayan, N. (Nandini), Jakobsdottir, M. (Margret), Kunkle, B.W. (B. W.), Boland, A. (A.), Raybould, R. (R.), Bis, J.C. (Joshua), Martin, E.R. (E. R.), Grenier-Boley, B. (Benjamin), Heilmann-Heimbach, S. (S.), Chouraki, V. (V.), Kuzma, A.B. (A. B.), Sleegers, K. (K.), Vronskaya, M., Ruiz, A. (A.), Graham, R.R. (Robert), Olaso, R. (Robert), Hoffmann, P. (Per), Grove, M.L. (Megan), Vardarajan, B.N. (Badri), Hiltunen, M. (Mikko), Nöthen, M.M. (Markus), White, C.C. (Charles), Hamilton-Nelson, K.L. (K. L.), Epelbaum, J. (Jacques), Maier, W. (Wolfgang), Choi, S.H. (S. H.), Beecham, G.W., Dulary, C. (C.), Herms, S. (Stefan), Smith, A.V. (Albert), Funk, C.C. (C. C.), Derbois, (), Forstner, A.J. (Andreas), Ahmad, S. (S.), Li, H. (Huaixing), Bacq, D. (D.), Harold, D. (D.), Satizabal, C.L. (Claudia), Valladares, O. (Otto), Squassini, A. (Alessio), Thomas, R. (R.), Brody, J.A. (Jennifer A.), Qu, L. (Liming), Sanchez-Juan, P. (Pascual), Morgan, T. (Thomas), Wolters, F.J. (Frank), Zhao, Y. (Y.), Garcia, F.S. (F. S.), Denning, N. (Nicola), Fornage, M. (Myriam), Malamon, J. (J.), Naranjo, M.C.D. (M. C.D.), Majounie, E. (Elisa), Mosley, T.H. (Thomas H.), Dombroski, B. (B.), Wallon, D. (David), Lupton, M.K. (Michelle), Dupuis, J. (Josée), Whitehead, P. (P.), Fratiglioni, L. (L.), Medway, C. (Christopher), Jian, X. (X.), Mukherjee, S. (S.), Keller, L. (L.), Brown, K. (Kristelle), Lin, H. (Honghuang), Cantwell, L.B. (Laura B.), Panza, F. (F.), McGuinness, B. (B.), Moreno-Grau, S. (S.), Burgess, J.D. (J. D.), Solfrizzi, V. (Vincenzo), Proitsi, P. (P.), Adams, H.H.H. (Hieab), Allen, M. (M.), Seripa, D. (Davide), Pastor, P. (P.), Cupples, L.A. (L. A.), Price, N.D. (N. D.), Hannequin, D. (Didier), Frank-Garcia, A. (Ana), Levy, D. (D.), Chakrabarty, P. (P.), Caffarra, P. (Paolo), Giegling, I. (Ina), Beiser, A. (Alexa), Giedraitis, V. (Vilmantas), Hampel, H. (Heather), Garcia, M.E. (M.), Wang, X. (X.), Lannfelt, L. (Lars), Mecocci, P. (Patrizia), Eiriksdottir, G. (Gudny), Crane, L.M.A., Pasquier, F. (Florence), Boccardi, V. (V.), Henández, I. (I.), Barber, R.C. (R. C.), Scherer, M. (M.), Tárraga, L. (L.), Adams, P.M. (P. M.), Leber, I. (Isabelle), Chen, Y.D.I. (Yii-Der Ida), Albert, M. (Michael), Riedel-Heller, S. (Steffi), Emilsson, V. (Valur), Beekly, D. (D.), Braae, A. (A.), Schmidt, R. (R.), Blacker, D. (D.), Masullo, C., Schmidt, H. (Helena), Doody, R.S. (R. S.), Spalletta, G. (Gianfranco), Longstreth Jr, W.T., Fairchild, T.J. (T. J.), Bossù, P. (P.), Lopez, O.L. (Oscar), Frosch, M.P. (Matthew), Sacchinelli, E. (E.), Ghetti, B. (Bernardino), Yang, Q. (Qiong Fang), Huebinger, R.M. (R. M.), Jessen, F., Li, S. (S.), Kamboh, M.I. (M. I.), Morris, J. (J.), Sotolongo-Grau, O. (O.), Katz, M.J. (M. J.), Corcoran, C. (C.), Dunstan, M.L., Braddel, A. (A.), Thomas, C. (C.), Meggy, A. (A.), Marshall, R. (R.), Gerrish, A. (Amy), Chapman, J. (Jade), Aguilar, M. (M.), Taylor, S. (S.), Hill, M. (M.), Fairén, M.D. (M. D.), Hodges, A. (A.), Vellas, B. (B.), Soininen, H. (H.), Kloszewska, I. (Iwona), Daniilidou, M. (M.), Uphill, J. (James), Patel, Y. (Y.), Hughes, J.T. (J. 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(N.), Hanon, O. (Olivier), Dufouil, C. (Carole), Brice, A., Ritchie, K. (Karen), Dubois, B. (B.), Himali, J.J. (Jayandra), Keene, C.D. (C. D.), Tschanz, J. (J.), Fitzpatrick, A.L. (Annette), Kukull, W.A., Norton, M. (M.), Aspelund, T. (Thor), Larson, E.B. (Eric B.), Munger, R. (R.), Rotter, J.I. (Jerome I.), Lipton, R.B. (R. B.), Bullido, M.J. (Maria), Hofman, A. (A.), Montine, T.J. (T. J.), Coto, E. (Eliecer), Boerwinkle, E. (E.), Petersen, R.C. (R. C.), Alvarez, V. (V.), Rivadeneira Ramirez, F. (Fernando), Reiman, E.M. (Eric), Gallo, V. (Valentina), O'Donnell, C.J. (Christopher), Reisch, J.S. (J. S.), Bruni, A.C. (Amalia), Royall, D.R. (D. R.), Kubisch, C. (Christian), Sano, M. (M.), Galimberti, D. (Daniela), St. George-Hyslop, P. (Peter), Scarpini, E. (Elio), Tsuang, D.W. (Debby W.), Mancuso, M. (M.), Bonuccelli, U. (Ubaldo), Winslow, A.R. (A. R.), Daniele, A. (A.), Wu, C.K. (C. K.), Peters, O. (Oscar), Nacmias, B. (Benedetta), Riemenschneider, M. (M.), Heun, R. (Reinhard), Brayne, C. (Carol), Rubinsztein, D.C. (David), Bras, J. (J.), Guerreiro, R. (R.), Al-Chalabi, A. (Ammar), Shaw, C.E. (C. E.), Collinge, J. (J.), Mann, D. (D.), Tsolaki, M. (Magda), Clarimón, J. (J.), Sussams, R. (R.), Lovestone, S. (Simon), O'donovan, M.C. (Michael), Owen, M.J. (Michael), Behrens, T.W. (Timothy), Mead, S. (S.), Goate, A.M. (Alison), Uitterlinden, A.G. (A. G.), Holmes, C. (C.), Cruchaga, C. (Carlos), Ingelsson, M. (Martin), Bennett, D.A. (David), Powell, J. (J.), Golde, T.E. (T. E.), Graff, C. (C.), De Jager, P., Morgan, K. (Kevin), Ertekin-Taner, N. (N.), Combarros, O. (Onofre), Psaty, B.M. (Bruce), Passmore, P. (P.), Younkin, S.G. (S. G.), Berr, C. (Claudine), Gudnason, V. (Vilmundur), Rujescu, D. (D.), Dickson, D. (Dennis), Dartigues, J.-F., DeStefano, A.L. (Anita), Ortega-Cubero, S. (S.), Hakonarson, H. (Hakon), Campion, D. (Dominique), Boada, M. (M.), Kauwe, J.K. (J. K.), Farrer, L.A. (Lindsay), Broeckhoven, C. (Christine) van, Ikram, M.A. (Arfan), Jones, L. (L.), Haines, J.L. (Jonathan), Tzourio, C. (Christophe), Launer, L.J. (Lenore), Escott-Price, V. (V.), Mayeux, R. (R.), Deleuze, J.-F. (Jean-François), Amin, N. (Najaf), Holmans, P.A. (Peter A.), Kunkle, B. (Brian), Amouyel, P. (Philippe), Duijn, C.M. (Cornelia) van, Ramirez, A. (Alfredo), Wang, L.S. (L. S.), Lambert, J.-C. (J.), Seshadri, S. (Sudha), Williams, J. (J.), Schellenberg, G.D. (Gerard), Destefano, A.L. (Anita L.), and Seshardi, S. (Sudha)

Abstract

Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C. Methods: Ten single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger. Results: Based on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P >.7). Discussion: Our study does not support the role of HDL-C on risk of AD through HDL-C altered b

Published
2018
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8. A novel Alzheimer disease locus located near the gene encoding tau protein

Author

Jun, G., Ibrahim-Verbaas, C.A., Vronskaya, M., Lambert, J.-., Chung, J., Naj, A.C., Kunkle, B.W., Wang, L.-., Bis, J.C., Bellenguez, C., Harold, D., Lunetta, K.L., Destefano, A.L., Grenier-Boley, B., Sims, R., Beecham, G.W., Smith, A.V., Chouraki, V., Hamilton-Nelson, K.L., Ikram, M.A., Fievet, N., Denning, N., Martin, E.R., Schmidt, H., Kamatani, Y., Dunstan, M.L., Valladares, O., Laza, A.R., Zelenika, D., Ramirez, A., Foroud, T.M., Choi, S.-., Boland, A., Becker, T., Kukull, W.A., Van Der Lee, S.J., Pasquier, F., Cruchaga, C., Beekly, D., Fitzpatrick, A.L., Hanon, O., Gill, M., Barber, R., Gudnason, V., Campion, D., Love, S., Bennett, D.A., Amin, N., Berr, C., Tsolaki, M., Buxbaum, J.D., Lopez, O.L., Deramecourt, V., Fox, N.C., Cantwell, L.B., Tárraga, L., Dufouil, C., Hardy, J., Crane, P.K., Eiriksdottir, G., Hannequin, D., Clarke, R., Evans, D., Mosley, T.H., Letenneur, L., Brayne, C., Maier, W., De Jager, P., Emilsson, V., Dartigues, J.-., Hampel, H., Kamboh, M.I., De Bruijn, R.F.A.G., Tzourio, C., Pastor, P., Larson, E.B., Rotter, J.I., O'Donovan, M.C., Montine, T.J., Nalls, M.A., Mead, S., Reiman, E.M., Jonsson, P.V., Holmes, C., St George-Hyslop, P.H., Boada, M., Passmore, P., Wendland, J.R., Schmidt, R., Morgan, K., Winslow, A.R., Powell, J.F., Carasquillo, M., Younkin, S.G., Jakobsdóttir, J., Kauwe, J.S.K., Wilhelmsen, K.C., Rujescu, D., Nöthen, M.M., Hofman, A., Jones, L., Haines, J.L., Psaty, B.M., Van Broeckhoven, C., Holmans, P., Launer, L.J., Mayeux, R., Lathrop, M., Goate, A.M., Escott-Price, V., Seshadri, S., Pericak-Vance, M.A., Amouyel, P., Williams, J., Van Duijn, C.M., Schellenberg, G.D., Farrer, L.A., Adams, P.M., Albert, M.S., Albin, R.L., Apostolova, L.G., Arnold, S.E., Asthana, S., Atwood, C.S., Baldwin, C.T., Barmada, M.M., Barnes, L.L., Beach, T.G., Becker, J.T., Bigio, E.H., Bird, T.D., Blacker, D., Boeve, B.F., Bowen, J.D., Boxer, A., Burke, J.R., Cairns, N.J., Cao, C., Carlson, C.S., Carlsson, C.M., Carney, R.M., Carrasquillo, M.M., Carroll, S.L., Chui, H.C., Clark, D.G., Corneveaux, J., Cribbs, D.H., Crocco, E.A., De Jager, P.L., Decarli, C., Dekosky, S.T., Yesim Demirci, F., Dick, M., Dickson, D.W., Doody, R.S., Duara, R., Ertekin-Taner, N., Faber, K.M., Fairchild, T.J., Fallon, K.B., Farlow, M.R., Ferris, S., Frosch, M.P., Galasko, D.R., Gearing, M., Geschwind, D.H., Ghetti, B., Gilbert, J.R., Glass, J.D., Graff-Radford, N.R., Green, R.C., Growdon, J.H., Hakonarson, H., Hamilton, R.L., Harrell, L.E., Head, E., Honig, L.S., Huebinger, R.M., Huentelman, M.J., Hulette, C.M., Hyman, B.T., Jarvik, G.P., Jicha, G.A., Jin, L., Karydas, A., Kaye, J.A., Kim, R., Koo, E.H., Kowall, N.W., Kramer, J.H., Laferla, F.M., Lah, J.J., Leverenz, J.B., Levey, A.I., Ge, L., Lieberman, A.P., Lin, C., Lyketsos, C.G., Mack, W.J., Marson, D.C., Martiniuk, F., Mash, D.C., Masliah, E., Mccormick, W.C., Mccurry, S.M., Mcdavid, A.N., Mckee, A.C., Mesulam, M., Miller, B.L., Miller, C.A., Miller, J.W., Morris, J.C., Mukherjee, S., Murrell, J.R., Myers, A.J., O'Bryant, S., Olichney, J.M., Pankratz, V.S., Parisi, J.E., Partch, A., Paulson, H.L., Perry, W., Peskind, E., Petersen, R.C., Pierce, A., Poon, W.W., Potter, H., Quinn, J.F., Raj, A., Raskind, M., Reisberg, B., Reisch, J.S., Reitz, C., Ringman, J.M., Roberson, E.D., Rogaeva, E., Rosen, H.J., Rosenberg, R.N., Royall, D.R., Sager, M.A., Sano, M., Saykin, A.J., Schneider, J.A., Schneider, L.S., Seeley, W.W., Smith, A.G., Sonnen, J.A., Spina, S., Stern, R.A., Tanzi, R.E., Thornton-Wells, T.A., Trojanowski, J.Q., Troncoso, J.C., Tsuang, D.W., Van Deerlin, V.M., Van Eldik, L.J., Vardarajan, B.N., Vinters, H.V., Vonsattel, J.P., Weintraub, S., Welsh-Bohmer, K.A., Williamson, J., Wishnek, S., Woltjer, R.L., Wright, C.B., Chuang-Kuo, W., Chang-En, Y., Lei, Y., Thomas, C., Gerrish, A., Chapman, J., Stretton, A., Morgan, A., Oldham, H., Owen, M.J., Kehoe, P.G., Medway, C., Brown, K., Lord, J., Turton, J., Hooper, N.M., Vardy, E., Warren, J.D., Schott, J.M., Uphill, J., Hollingworth, P., Ryan, N., Rossor, M., Collinge, J., Ben-Shlomo, Y., Makrina, D., Gkatzima, O., Lupton, M., Koutroumani, M., Avramidou, D., Germanou, A., Jessen, F., Riedel-Heller, S., Dichgans, M., Heun, R., Kölsch, H., Schürmann, B., Herold, C., Lacour, A., Drichel, D., Hoffmann, P., Kornhuber, J., Wei, G., Feulner, T., Mayhaus, M., Pichler, S., Riemenschneider, M., van den Bussche, H., Lawlor, B., Lynch, A., Mann, D., Smith, A.D., Warden, D., Wilcock, G., Heuser, I., Wiltfang, J., Frölich, L., Hüll, M., Mayo, K., Livingston, G., Bass, N.J., Gurling, H., Mcquillin, A., Gwilliam, R., Deloukas, P., Al-Chalabi, A., Shaw, C.E., Singleton, A.B., Guerreiro, R., Russo, G., Jöckel, K., Moebus, S., Klopp, N., Wichmann, H.-., Li, M., Bisceglio, G., Fisher, E., Warner, N., Pickering-Brown, S., Craig, D., Johnston, J.A., Mcguinness, B., Todd, S., Rubinsztein, D.C., Lovestone, S., Bayer, A., Gallacher, J., Proitsi, P., Ortega-Cubero, Saraadams, P., Albert, M., Albin, R., Apostolova, L., Arnold, S., Atwood, C., Baldwin, C., Barmada, M., Barnes, L., Beach, T., Becker, J., Bigio, E., Bird, T., Boeve, B., Bowen, J., Burke, J., Cairns, N., Carlson, C., Carlsson, C., Carney, R., Carrasquillo, M., Carroll, S., Chui, H., Clark, D., Cribbs, D., Crocco, E., De Jager PL, Dekosky, S., Demirci, F., Dickson, D., Doody, R., Faber, K., Fairchild, T., Fallon, K., Farlow, M., Frosch, M., Galasko, D., Geschwind, D., Gilbert, J., Glass, J., Graff-Radford, N., Green, R., Growdon, J., Hamilton, R., Harrell, L., Honig, L., Huebinger, R., Huentelman, M., Hulette, C., Hyman, B., Jarvik, G., Jicha, G., Kauwe, J., Kaye, J., Koo, E., Kowall, N., Kramer, J., Laferla, F., Lah, J., Leverenz, J., Levey, A., Li, G., Lieberman, A., Lopez, O., Lyketsos, C., Mack, W., Marson, D., Mash, D., Mccormick, W., Mccurry, S., Mcdavid, A., Mckee, A., Miller, B., Miller, C., Miller, J., Morris, J., Murrell, J., Myers, A., Olichney, J., Pankratz, V., Parisi, J., Paulson, H., Petersen, R., Poon, W., Quinn, J., Reisch, J., Ringman, J., Roberson, E., Rosen, H., Rosenberg, R., Royall, D., Sager, M., Saykin, A., Schneider, J., Schneider, L., Seeley, W., Smith, A., Sonnen, J., Stern, R., Tanzi, R., Thornton-Wells, T., Trojanowski, J., Troncoso, J., Tsuang, D., Van Deerlin VM, Van Eldik LJ, Vardarajan, B., Vinters, H., Vonsattel, J., Welsh-Bohmer, K., Woltjer, R., Wright, C., Wu, C., Yu, C., Yu, L., Au, R., Wolf, P., Beiser, A., Satizabal, C., Uitterlinden, A., Rivadeneira, F., Koudstaal, P., Longstreth WT Jr, Kuller, L., Lumley, T., Rice, K., Harris, T., Nalls, M., Marksteiner, J., Dal-Bianco, P., Töglhofer, A., Freudenberger, P., Ransmayr, G., Benke, T., Toeglhofer, A., Boerwinkle, E., Bressler, J., Fornage, M., Morón, F., Hernández, I., Roca, M., Mauleón, A., Alegret, M., Ramírez-Lorca, R., González-Perez, A., Alpérovitch, A., Alvarez, V., Barberger-Gateau, P., Bettens, K., Bossù, P., Brice, A., Bullido, M., Caffara, P., Clarimon, J., Combarros, O., Coto, E., Del Zampo, M., Delepine, M., Deniz Naranjo MC, Epelbaum, J., Fratiglioni, L., Galimberti, D., Graff, C., Hiltunen, M., Ingelsson, M., Keller, L., Lannfelt, L., Llèo, A., Mancuso, M., Mateo, I., Mecocci, P., Nacmias, B., Panza, F., Pilotto, A., Garcia, F., Scarpini, E., Seripa, D., Sleegers, K., Soininen, H., Sorbi, S., Spalletta, G., Wallon, D., Owen, M., Kehoe, P., Hooper, N., Warren, J., Schott, J., Gu, W., Bass, N., Shaw, C., Singleton, A., Wichmann, H., Ma, L., Johnston, J., Rubinsztein, D., Ortega-Cubero, S., Epidemiology, Neurology, and Internal Medicine

Subjects
0301 basic medicine, Apolipoprotein E, Apolipoprotein E4, Single-nucleotide polymorphism, Locus (genetics), Genome-wide association study, genetics [Alzheimer Disease], MAPT protein, human, tau Proteins, Polymorphism, Single Nucleotide, Article, Chromosomes, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Alzheimer Disease, Settore BIO/13 - Biologia Applicata, Humans, ddc:610, Polymorphism, Molecular Biology, Biology, genetics [Apolipoprotein E4], Genetic association, Temporal cortex, Genetics, Pair 17, Haplotype, Single Nucleotide, 3. Good health, Chromosome 17 (human), genetics [tau Proteins], Chemistry, 030104 developmental biology, Psychiatry and Mental Health, Chromosomes, Human, Pair 17, Genome-Wide Association Study, Settore MED/26 - Neurologia, Human medicine, Psychology, 030217 neurology & neurosurgery, Human
Abstract

APOE epsilon 4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE epsilon 4+ (10 352 cases and 9207 controls) and APOE epsilon 4 - (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE e4 status. Suggestive associations (P < 1x10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE epsilon 4+: 1250 cases and 536 controls; APOE epsilon 4 -: 718 cases and 1699 controls). Among APOE epsilon 4 - subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P = 5.8 x 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE epsilon 4+ subjects (CR1 and CLU) or APOE epsilon 4 - subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P = 1.6 x 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P

Published
2016
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10. Cognitive activity and the cognitive morbidity of Alzheimer disease(e–Pub ahead of print)

Author

Wilson, R.S., Barnes, L.L., Aggarwal, N.T., Boyle, P.A., Hebert, L.E., Mendes de Leon, C.F., and Evans, D.A.

Subjects
Male, Articles, Neuropsychological Tests, Cognition, Socioeconomic Factors, Alzheimer Disease, Data Interpretation, Statistical, Disease Progression, Humans, Female, Longitudinal Studies, Cognition Disorders, Aged, Follow-Up Studies
Abstract

To test the hypothesis that frequent cognitive activity predicts slower cognitive decline before dementia onset in Alzheimer disease (AD) and faster decline thereafter.As part of a longitudinal cohort study, older residents of a geographically defined population were assessed at 3-year intervals with brief cognitive performance tests from which a composite measure of global cognition was derived. After each wave of testing, a subset was sampled for clinical evaluation. The present analyses are based on 1,157 participants. They were free of dementia at study enrollment at which time they rated frequency of participation in common cognitively stimulating activities from which a previously validated summary measure was derived. They were sampled for clinical evaluation a mean of 5.6 years after enrollment and subsequently followed a mean of 5.7 years with brief cognitive performance testing at 3-year intervals.On clinical evaluation, 614 people had no cognitive impairment, 395 had mild cognitive impairment, and 148 had AD. During follow-up, the annual rate of global cognitive decline in persons without cognitive impairment was reduced by 52% (estimate = 0.029, SE = 0.010, p = 0.003) for each additional point on the cognitive activity scale. In the mild cognitive impairment group, cognitive decline rate was unrelated to cognitive activity (estimate = -0.019, SE = 0.018, p = 0.300). In AD, the mean rate of decline per year increased by 42% (estimate = 0.075, SE = 0.021, p0.001) for each point on the cognitive activity scale.Mentally stimulating activity in old age appears to compress the cognitive morbidity associated with AD by slowing cognitive decline before dementia onset and hastening it thereafter.

Published
2010

12. Effects of warning signals and fixation point offsets on the latencies of pro- versus antisaccades: implications for an interpretation of the gap effect

Author

Department of Psychology, University of Michigan, 525 East University, 48109-1109, Ann Arbor, MI, USA, Department of Psychology, Dartmouth College, 03755, Hanover, NH, USA, Department of Psychology, University of Washington, 63130, St. Louis, MO, USA, Ann Arbor, Hughes, H.C., Oonk, H.M., Barnes, L.L., Reuter-Lorenz, Patricia A., Department of Psychology, University of Michigan, 525 East University, 48109-1109, Ann Arbor, MI, USA, Department of Psychology, Dartmouth College, 03755, Hanover, NH, USA, Department of Psychology, University of Washington, 63130, St. Louis, MO, USA, Ann Arbor, Hughes, H.C., Oonk, H.M., Barnes, L.L., and Reuter-Lorenz, Patricia A.

Abstract

The present study was designed to evaluate whether fixation point offsets have the same effects on the average latencies of prosaccades (responses towards target) and antisaccades (responses away from target). Gap and overlap conditions were run with and without an acoustic warning signal. The???gap effect??? was taken to be the difference in mean reaction time between gap and overlap trials. This effect was dramatically reduced by the presentation of the warning signal. Without this signal, fixation offsets can serve as warning signals themselves, which artifactually inflates the magnitude of the gap effect. The warning effect of fixation offsets was equivalent for pro and antisaccades. A significant gap effect is still evident with the acoustic warning signal; however, in this case it is associated primarily with prosaccades. These results replicate and extend our previous work demonstrating that, if their warning effects are controlled, the facilitatory effects of fixation point offsets are response dependent, and suggesting the existence of a component process (fixation release) which is closely linked with the processing architecture underlying target-directed saccades.

Published
2006

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