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Your search keyword '"Chouraki, V."' showing total 18 results
Start Over Author "Chouraki, V." Publisher nature publishing group
18 results on '"Chouraki, V."'

1. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates A beta, tau, immunity and lipid processing (vol 51, pg 414, 2019)

Author

Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Damotte, V, Naj, AC, Boland, A, Vronskaya, M, van der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Moreno-Grau, S, Olaso, R, Raybould, R, Chen, YN, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, LM, Bacq, D, Denning, N, Jian, XQ, Zhao, Y, Del Zompo, M, Fox, NC, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Sanchez-Garcia, F, Patel, Y, Brody, JA, Dombroski, BA, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewicz, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, WS, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Sordon, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Munoz-Fernadez, C, Sussams, R, Lin, HH, Fairchild, TJ, Benito, YA, Holmes, C, Karamujic-Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roshchupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernandez, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth, WT, Montine, TJ, Frisardi, V, Diez-Fairen, M, Rivadeneira, F, Petersen, RC, Deramecourt, V, Alvarez, I, Salani, F, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AGA, Royall, DR, Dufouil, C, Maletta, RG, de Rojas, I, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Quintela, I, Carracedo, A, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frolich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JA, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, JR, Kauwe, JSK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, CH, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Kolsch, H, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hull, M, Geschwind, DH, Gilbert, JR, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, GE, Jin, LW, Leonenko, G, Real, LM, Jun, GR, Baldwin, CT, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jockel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nothen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, Mckee, AC, van den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O'Bryant, S, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, WR, Mead, S, Peskind, E, Cribbs, DH, Rossor, M, Pierce, A, Ryan, NS, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Caltagirone, C, Bossu, P, Orfei, MD, Reisberg, B, Clarke, R, Reitz, C, Smith, AD, Ringman, JM, Warden, D, Roberson, ED, Wilcock, G, Rogaeva, E, Bruni, AC, Rosen, HJ, Gallo, M, Rosenberg, RN, Ben-Shlomo, Y, Sager, MA, Mecocci, P, Saykin, AJ, Pastor, P, Cuccaro, ML, Vance, JM, Schneider, JA, Schneider, LS, Slifer, S, Seeley, WW, Smith, AG, Sonnen, JA, Spina, S, Stern, RA, Swerdlow, RH, Tang, M, Tanzi, RE, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Van Eldik, LJ, Vinters, HV, Vonsattel, JP, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, Woltjer, RL, Wright, CB, Yu, CE, Yu, L, Saba, Y, Pilotto, A, Bullido, MJ, Peters, O, Crane, PK, Bennett, D, Bosco, P, Coto, E, Boccardi, V, De Jager, PL, Lleo, A, Warner, N, Lopez, OL, Ingelsson, M, Deloukas, P, Cruchaga, C, Graff, C, Gwilliam, R, Fornage, M, Goate, AM, Sanchez-Juan, P, Kehoe, PG, Amin, N, Ertekin-Taner, N, Berr, C, Debette, S, Love, S, Launer, LJ, Younkin, SG, Dartigues, JF, Corcoran, C, Ikram, MA, Dickson, DW, Nicolas, G, Campion, D, Tschanz, J, Schmidt, H, Hakonarson, H, Clarimon, J, Munger, R, Schmidt, R, Farrer, LA, Van Broeckhoven, C, O'Donovan, MC, DeStefano, AL, Jones, L, Haines, JL, Deleuze, JF, Owen, MJ, Gudnason, V, Mayeux, R, Escott-Price, V, Psaty, BM, Ramirez, A, Wang, LS, Ruiz, A, van Duijn, CM, Holmans, PA, Seshadri, S, Williams, J, Amouyel, P, Schellenberg, GD, Lambert, JC, Pericak-Vance, MA, ADGC, EADI, Cohorts Heart Aging Res Genomic, and Genetic Environm Risk AD Defining

Published
2019

2. Nat Genet

Author

KUNKLE, B. W., GRENIER-BOLEY, B., SIMS, R., BIS, J. C., DAMOTTE, V., NAJ, A. C., BOLAND, A., VRONSKAYA, M., VAN DER LEE, S. J., AMLIE-WOLF, A., BELLENGUEZ, C., FRIZATTI, A., CHOURAKI, V., MARTIN, E. R., SLEEGERS, K., BADARINARAYAN, N., JAKOBSDOTTIR, J., HAMILTON-NELSON, K. L., MORENO-GRAU, S., OLASO, R., RAYBOULD, R., CHEN, Y., KUZMA, A. B., HILTUNEN, M., MORGAN, T., AHMAD, S., VARDARAJAN, B. N., EPELBAUM, J., HOFFMANN, P., BOADA, M., BEECHAM, G. W., GARNIER, J. G., HAROLD, D., FITZPATRICK, A. L., VALLADARES, O., MOUTET, M. L., GERRISH, A., QU, L., BACQ, D., DENNING, N., JIAN, X., ZHAO, Y., DEL ZOMPO, M., FOX, N. C., CHOI, S. H., MATEO, I., HUGHES, J. T., ADAMS, H. H., MALAMON, J., SANCHEZ-GARCIA, F., PATEL, Y., BRODY, J. A., DOMBROSKI, B. A., NARANJO, M. C. D., DANIILIDOU, M., EIRIKSDOTTIR, G., MUKHERJEE, S., WALLON, D., UPHILL, J., ASPELUND, T., CANTWELL, L. B., GARZIA, F., GALIMBERTI, D., HOFER, E., BUTKIEWICZ, M., FIN, B., SCARPINI, E., SARNOWSKI, C., BUSH, W. S., MESLAGE, S., KORNHUBER, J., WHITE, C. C., SONG, Y., BARBER, R. C., ENGELBORGHS, S., SORDON, S., VOIJNOVIC, D., ADAMS, P. M., VANDENBERGHE, R., MAYHAUS, M., CUPPLES, L. A., ALBERT, M. S., DE DEYN, P. P., GU, W., HIMALI, J. J., BEEKLY, D., SQUASSINA, A., HARTMANN, A. M., ORELLANA, A., BLACKER, D., RODRIGUEZ-RODRIGUEZ, E., LOVESTONE, S., GARCIA, M. E., DOODY, R. S., MUNOZ-FERNADEZ, C., SUSSAMS, R., LIN, H., FAIRCHILD, T. J., BENITO, Y. A., HOLMES, C., KARAMUJIC-COMIC, H., FROSCH, M. P., THONBERG, H., MAIER, W., ROSCHUPKIN, G., GHETTI, B., GIEDRAITIS, V., KAWALIA, A., LI, S., HUEBINGER, R. M., KILANDER, L., MOEBUS, S., HERNANDEZ, I., KAMBOH, M. I., BRUNDIN, R., TURTON, J., YANG, Q., KATZ, M. J., CONCARI, L., LORD, J., BEISER, A. S., KEENE, C. D., HELISALMI, S., KLOSZEWSKA, I., KUKULL, W. A., KOIVISTO, A. M., LYNCH, A., TARRAGA, L., LARSON, E. B., HAAPASALO, A., LAWLOR, B., MOSLEY, T. H., LIPTON, R. B., SOLFRIZZI, V., GILL, M., LONGSTRETH, W. T. Jr., MONTINE, T. J., FRISARDI, V., DIEZ-FAIREN, M., RIVADENEIRA, F., PETERSEN, R. C., DERAMECOURT, V., ALVAREZ, I., SALANI, F., CIARAMELLA, A., BOERWINKLE, E., REIMAN, E. M., FIEVET, N., ROTTER, J. I., REISCH, J. S., HANON, O., CUPIDI, C., ANDRE UITTERLINDEN, A. G., ROYALL, D. R., DUFOUIL, Carole, MALETTA, R. G., DE ROJAS, I., SANO, M., BRICE, A., CECCHETTI, R., GEORGE-HYSLOP, P. S., RITCHIE, K., TSOLAKI, M., TSUANG, D. W., DUBOIS, B., CRAIG, D., WU, C. K., SOININEN, H., AVRAMIDOU, D., ALBIN, R. L., FRATIGLIONI, L., GERMANOU, A., APOSTOLOVA, L. G., KELLER, L., KOUTROUMANI, M., ARNOLD, S. E., PANZA, F., GKATZIMA, O., ASTHANA, S., HANNEQUIN, D., WHITEHEAD, P., ATWOOD, C. S., CAFFARRA, P., HAMPEL, H., QUINTELA, I., CARRACEDO, A., LANNFELT, L., RUBINSZTEIN, D. C., BARNES, L. L., PASQUIER, F., FROLICH, L., BARRAL, S., MCGUINNESS, B., BEACH, T. G., JOHNSTON, J. A., BECKER, J. T., PASSMORE, P., BIGIO, E. H., SCHOTT, J. M., BIRD, T. D., WARREN, J. D., BOEVE, B. F., LUPTON, M. K., BOWEN, J. D., PROITSI, P., BOXER, A., POWELL, J. F., BURKE, J. R., KAUWE, J. S. K., BURNS, J. M., MANCUSO, M., BUXBAUM, J. D., BONUCCELLI, U., CAIRNS, N. J., MCQUILLIN, A., CAO, C., LIVINGSTON, G., CARLSON, C. S., BASS, N. J., CARLSSON, C. M., HARDY, J., CARNEY, R. M., BRAS, J., CARRASQUILLO, M. M., GUERREIRO, R., ALLEN, M., CHUI, H. C., FISHER, E., MASULLO, C., CROCCO, E. A., DECARLI, C., BISCEGLIO, G., DICK, M., MA, L., DUARA, R., GRAFF-RADFORD, N. R., EVANS, D. A., HODGES, A., FABER, K. M., SCHERER, M., FALLON, K. B., RIEMENSCHNEIDER, M., FARDO, D. W., HEUN, R., FARLOW, M. R., KOLSCH, H., FERRIS, S., LEBER, M., FOROUD, T. M., HEUSER, I., GALASKO, D. R., GIEGLING, I., GEARING, M., HULL, M., GESCHWIND, D. H., GILBERT, J. R., GREEN, R. C., MAYO, K., GROWDON, J. H., FEULNER, T., HAMILTON, R. L., HARRELL, L. E., DRICHEL, D., HONIG, L. S., CUSHION, T. D., HUENTELMAN, M. J., HOLLINGWORTH, P., HULETTE, C. M., HYMAN, B. T., MARSHALL, R., JARVIK, G. P., MEGGY, A., ABNER, E., MENZIES, G. E., JIN, L. W., LEONENKO, G., REAL, L. M., JUN, G. R., BALDWIN, C. T., GROZEVA, D., KARYDAS, A., RUSSO, G., KAYE, J. A., KIM, R., JESSEN, F., KOWALL, N. W., VELLAS, B., KRAMER, J. H., VARDY, E., LAFERLA, F. M., JOCKEL, K. H., LAH, J. J., DICHGANS, M., LEVERENZ, J. B., MANN, D., LEVEY, A. I., PICKERING-BROWN, S., LIEBERMAN, A. P., KLOPP, N., LUNETTA, K. L., WICHMANN, H. E., LYKETSOS, C. G., MORGAN, K., MARSON, D. C., BROWN, K., MARTINIUK, F., MEDWAY, C., MASH, D. C., NOTHEN, M. M., MASLIAH, E., HOOPER, N. M., MCCORMICK, W. C., DANIELE, A., MCCURRY, S. M., BAYER, A., MCDAVID, A. N., GALLACHER, J., MCKEE, A. C., VAN DEN BUSSCHE, H., MESULAM, M., BRAYNE, C., MILLER, B. L., RIEDEL-HELLER, S., MILLER, C. A., MILLER, J. W., AL-CHALABI, A., MORRIS, J. C., SHAW, C. E., MYERS, A. J., WILTFANG, J., O'BRYANT, S., OLICHNEY, J. M., ALVAREZ, V., PARISI, J. E., SINGLETON, A. B., PAULSON, H. L., COLLINGE, J., PERRY, W. R., MEAD, S., PESKIND, E., CRIBBS, D. H., ROSSOR, M., PIERCE, A., RYAN, N. S., POON, W. W., NACMIAS, B., POTTER, H., SORBI, S., QUINN, J. F., SACCHINELLI, E., RAJ, A., SPALLETTA, G., RASKIND, M., CALTAGIRONE, C., BOSSU, P., ORFEI, M. D., REISBERG, B., CLARKE, R., REITZ, C., RINGMAN, J. M., WARDEN, D., ROBERSON, E. D., WILCOCK, G., ROGAEVA, E., BRUNI, A. C., ROSEN, H. J., GALLO, M., ROSENBERG, R. N., BEN-SHLOMO, Y., SAGER, M. A., MECOCCI, P., SAYKIN, A. J., PASTOR, P., CUCCARO, M. L., VANCE, J. M., SCHNEIDER, J. A., SCHNEIDER, L. S., SLIFER, S., SEELEY, W. W., SMITH, A. V., SONNEN, J. A., SPINA, S., STERN, R. A., SWERDLOW, R. H., TANG, M., TANZI, R. E., 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., SABA, Y., ALZHEIMER DISEASE GENETICS, Consortium, EUROPEAN ALZHEIMER'S DISEASE, Initiative, COHORTS FOR, Heart, AGING RESEARCH IN GENOMIC EPIDEMIOLOGY, Consortium, GENETIC ENVIRONMENTAL RISK IN AD/DEFINING GENETIC, Polygenic, ENVIRONMENTAL RISK FOR ALZHEIMER'S DISEASE, Consortium, PILOTTO, A., BULLIDO, M. J., PETERS, O., CRANE, P. K., BENNETT, D., BOSCO, P., COTO, E., BOCCARDI, V., DE JAGER, P. L., LLEO, A., WARNER, N., LOPEZ, O. L., INGELSSON, M., DELOUKAS, P., CRUCHAGA, C., GRAFF, C., GWILLIAM, R., FORNAGE, M., GOATE, A. M., SANCHEZ-JUAN, P., KEHOE, P. G., AMIN, N., ERTEKIN-TANER, N., BERR, C., DEBETTE, S., LOVE, S., LAUNER, L. J., YOUNKIN, S. G., DARTIGUES, Jean-Francois, CORCORAN, C., IKRAM, M. A., DICKSON, D. W., NICOLAS, G., CAMPION, D., TSCHANZ, J., SCHMIDT, H., HAKONARSON, H., CLARIMON, J., MUNGER, R., SCHMIDT, R., FARRER, L. A., VAN BROECKHOVEN, C., M, C. O' Donovan, DESTEFANO, A. L., JONES, L., HAINES, J. L., DELEUZE, J. F., OWEN, M. J., GUDNASON, V., MAYEUX, R., ESCOTT-PRICE, V., PSATY, B. M., RAMIREZ, A., WANG, L. S., RUIZ, A., VAN DUIJN, C. M., HOLMANS, P. A., SESHADRI, S., WILLIAMS, J., AMOUYEL, P., SCHELLENBERG, G. D., LAMBERT, J. C., and PERICAK-VANCE, M. A.

Published
2019

3. Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (Nature Genetics, (2019), 51, 3, (414-430), 10.1038/s41588-019-0358-2)

Author

Kunkle, B. W., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., Boland, A., Vronskaya, M., van der Lee, S. J., Amlie-Wolf, A., Bellenguez, C., Frizatti, A., Chouraki, V., Martin, E. R., Sleegers, K., Badarinarayan, N., Jakobsdottir, J., Hamilton-Nelson, K. L., Moreno-Grau, S., Olaso, R., Raybould, R., Chen, Y., Kuzma, A. B., Hiltunen, M., Morgan, T., Ahmad, S., Vardarajan, B. N., Epelbaum, J., Hoffmann, P., Boada, M., Beecham, G. W., Garnier, J. -G., Harold, D., Fitzpatrick, A. L., Valladares, O., Moutet, M. -L., Gerrish, A., Smith, A. V., Qu, L., Bacq, D., Denning, N., Jian, X., Zhao, Y., Del Zompo, M., Fox, N. C., Choi, S. -H., Mateo, I., Hughes, J. T., Adams, H. H., Malamon, J., Sanchez-Garcia, F., Patel, Y., Brody, J. A., Dombroski, B. A., Naranjo, M. C. D., Daniilidou, M., Eiriksdottir, G., Mukherjee, S., Wallon, D., Uphill, J., Aspelund, T., Cantwell, L. B., Garzia, F., Galimberti, D., Hofer, E., Butkiewicz, M., Fin, B., Scarpini, E., Sarnowski, C., Bush, W. S., Meslage, S., Kornhuber, J., White, C. C., Song, Y., Barber, R. C., Engelborghs, S., Sordon, S., Voijnovic, D., Adams, P. M., Vandenberghe, R., Mayhaus, M., Cupples, L. A., Albert, M. S., De Deyn, P. P., Gu, W., Himali, J. J., Beekly, D., Squassina, A., Hartmann, A. M., Orellana, A., Blacker, D., Rodriguez-Rodriguez, E., Lovestone, S., Garcia, M. E., Doody, R. S., Munoz-Fernadez, C., Sussams, R., Lin, H., Fairchild, T. J., Benito, Y. A., Holmes, C., Karamujic-Comic, H., Frosch, M. P., Thonberg, H., Maier, W., Roshchupkin, G., Ghetti, B., Giedraitis, V., Kawalia, A., Li, S., Huebinger, R. M., Kilander, L., Moebus, S., Hernandez, I., Kamboh, M. I., Brundin, R. M., Turton, J., Yang, Q., Katz, M. J., Concari, L., Lord, J., Beiser, A. S., Keene, C. D., Helisalmi, S., Kloszewska, I., Kukull, W. A., Koivisto, A. M., Lynch, A., Tarraga, L., Larson, E. B., Haapasalo, A., Lawlor, B., Mosley, T. H., Lipton, R. B., Solfrizzi, V., Gill, M., Longstreth, W. T., Montine, T. J., Frisardi, V., Diez-Fairen, M., Rivadeneira, F., Petersen, R. C., Deramecourt, V., Alvarez, I., Salani, F., Ciaramella, A., Boerwinkle, E., Reiman, E. M., Fievet, N., Rotter, J. I., Reisch, J. S., Hanon, O., Cupidi, C., Uitterlinden, A. G. A., Royall, D. R., Dufouil, C., Maletta, R. G., de Rojas, I., Sano, M., Brice, A., Cecchetti, R., George-Hyslop, P. S., Ritchie, K., Tsolaki, M., Tsuang, D. W., Dubois, B., Craig, D., C. -K., Wu, Soininen, H., Avramidou, D., Albin, R. L., Fratiglioni, L., Germanou, A., Apostolova, L. G., Keller, L., Koutroumani, M., Arnold, S. E., Panza, F., Gkatzima, O., Asthana, S., Hannequin, D., Whitehead, P., Atwood, C. S., Caffarra, P., Hampel, H., Quintela, I., Carracedo, A., Lannfelt, L., Rubinsztein, D. C., Barnes, L. L., Pasquier, F., Frolich, L., Barral, S., Mcguinness, B., Beach, T. G., Johnston, J. A., Becker, J. T., Passmore, P., Bigio, E. H., Schott, J. M., Bird, T. D., Warren, J. D., Boeve, B. F., Lupton, M. K., Bowen, J. D., Proitsi, P., Boxer, A., Powell, J. F., Burke, J. R., Kauwe, J. S. K., Burns, J. M., Mancuso, M., Buxbaum, J. D., Bonuccelli, U., Cairns, N. J., Mcquillin, A., Cao, C., Livingston, G., Carlson, C. S., Bass, N. J., Carlsson, C. M., Hardy, J., Carney, R. M., Bras, J., Carrasquillo, M. M., Guerreiro, R., Allen, M., Chui, H. C., Fisher, E., Masullo, Carlo, Crocco, E. A., Decarli, C., Bisceglio, G., Dick, M., Ma, L., Duara, R., Graff-Radford, N. R., Evans, D. A., Hodges, A., Faber, K. M., Scherer, M., Fallon, K. B., Riemenschneider, M., Fardo, D. W., Heun, R., Farlow, M. R., Kolsch, H., Ferris, S., Leber, M., Foroud, T. M., Heuser, I., Galasko, D. R., Giegling, I., Gearing, M., Hull, M., Geschwind, D. H., Gilbert, J. R., Morris, J., Green, R. C., Mayo, K., Growdon, J. H., Feulner, T., Hamilton, R. L., Harrell, L. E., Drichel, D., Honig, L. S., Cushion, T. D., Huentelman, M. J., Hollingworth, P., Hulette, C. M., Hyman, B. T., Marshall, R., Jarvik, G. P., Meggy, A., Abner, E., Menzies, G. E., Jin, L. -W., Leonenko, G., Real, L. M., Jun, G. R., Baldwin, C. T., Grozeva, D., Karydas, A., Russo, G., Kaye, J. A., Kim, R., Jessen, F., Kowall, N. W., Vellas, B., Kramer, J. H., Vardy, E., Laferla, F. M., Jockel, K. -H., Lah, J. J., Dichgans, M., Leverenz, J. B., Mann, D., Levey, A. I., Pickering-Brown, S., Lieberman, A. P., Klopp, N., Lunetta, K. L., Wichmann, H. -E., Lyketsos, C. G., Morgan, K., Marson, D. C., Brown, K., Martiniuk, F., Medway, C., Mash, D. C., Nothen, M. M., Masliah, E., Hooper, N. M., Mccormick, W. C., Daniele, Antonio, Mccurry, S. M., Bayer, A., Mcdavid, A. N., Gallacher, J., Mckee, A. C., van den Bussche, H., Mesulam, M., Brayne, C., Miller, B. L., Riedel-Heller, S., Miller, C. A., Miller, J. W., Al-Chalabi, A., Morris, J. C., Shaw, C. E., Myers, A. J., Wiltfang, J., O'Bryant, S., Olichney, J. M., Alvarez, V., Parisi, J. E., Singleton, A. B., Paulson, H. L., Collinge, J., Perry, W. R., Mead, S., Peskind, E., Cribbs, D. H., Rossor, M., Pierce, A., Ryan, N. S., Poon, W. W., Nacmias, B., Potter, H., Sorbi, S., Quinn, J. F., Sacchinelli, E., Raj, A., Spalletta, Gianfranco, Raskind, M., Caltagirone, C., Bossu, P., Orfei, M. D., Reisberg, B., Clarke, Ronald Victor, Reitz, C., Smith, A. D., Ringman, J. M., Warden, D., Roberson, E. D., Wilcock, G., Rogaeva, E., Bruni, A. C., Rosen, H. J., Gallo, Massimiliano, Rosenberg, R. N., Ben-Shlomo, Y., Sager, M. A., Mecocci, P., Saykin, A. J., Pastor, P., Cuccaro, M. L., Vance, J. M., Schneider, J. A., Schneider, L. S., Slifer, S., Seeley, W. W., Smith, A. G., Sonnen, J. A., Spina, S., Stern, R. A., Swerdlow, R. H., Tang, M., Tanzi, R. E., 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., C. -E., Yu, Yu, L., Saba, Y., Pilotto, A., Bullido, M. J., Peters, O., Crane, P. K., Bennett, D., Bosco, P., Coto, E., Boccardi, V., De Jager, P. L., Lleo, A., Warner, N., Lopez, O. L., Ingelsson, M., Deloukas, P., Cruchaga, C., Graff, C., Gwilliam, R., Fornage, M., Goate, A. M., Sanchez-Juan, P., Kehoe, P. G., Amin, N., Ertekin-Taner, N., Berr, C., Debette, S., Love, S., Launer, L. J., Younkin, S. G., Dartigues, J. -F., Corcoran, C., Ikram, M. A., Dickson, D. W., Nicolas, G., Campion, D., Tschanz, J. A., Schmidt, H., Hakonarson, H., Clarimon, J., Munger, R., Schmidt, R., Farrer, L. A., Van Broeckhoven, C., O'Donovan, M. C., Destefano, A. L., Jones, L., Haines, J. L., Deleuze, J. -F., Owen, M. J., Gudnason, V., Mayeux, R., Escott-Price, V., Psaty, B. M., Ramirez, A., Wang, L. -S., Ruiz, A., van Duijn, C. M., Holmans, P. A., Seshadri, S., Williams, J., Amouyel, P., Schellenberg, G. D., Lambert, J. -C., and Pericak-Vance, M. A.

Subjects
Author Correction: Alzheimer’s disease genetic meta-analysis new risk loci Aβ, tau, immunity and lipid processing, Settore MED/26 - NEUROLOGIA, Author Correction: Alzheimer’s disease genetic meta-analysis new risk loci Aβ, tau, immunity and lipid processing
Published
2019

4. Novel genetic loci associated with hippocampal volume

Author

Hibar, D.P., Adams, H.H.H., Jahanshad, N., Chauhan, G., Stein, J.L., Hofer, E., Renteria, M.E., Bis, J.C., Arias-Vasquez, A., Ikram, M.K., Desrivières, S., Vernooij, M.W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beecham, A.H., Beiser, A., Bernard, M., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chen, Q., Ching, C.R.K., Chouraki, V., Cuellar-Partida, G., Crivello, F., den Braber, A., Doan, N.T., Ehrlich, S., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Grimm, O., Griswold, M.E., Guadalupe, T., Gutman, B.A., Hass, J., Haukvik, U.K., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K.N., Karbalai, N., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A.F., Matarin, M., Mather, K.A., Mattheisen, M., McKay, D.R., Milaneschi, Y., Munoz Maniega, S., Nho, K., Nugent, A.C., Nyquist, P., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Putz, B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Saremi, A., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Trompet, S., Vaidya, D., Van der Grond, J., van der Lee, S.J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Wolfers, T., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., de Craen, A.J.M., de Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Deary, I.J., Debette, S., DeCarli, C., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Enzinger, C., Erk, S., Espeseth, T., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Fornage, M., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Håberg, A.K., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Huentelman, M., Pol, H.E.H., Ikeda, M., Jack Jr, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schmidt, H., Schofield, P.R., Sigursson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Tsolaki, M., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., van der Lugt, A., van der Wee, N.J.A., van Haren, N.E.M., van ’t Ent, D., van Tol, M-J, Vardarajan, B.N., Vellas, B., Veltman, D.J., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, R.H., Zonderman, A.B., Martin, N.G., van Duijn, C.M., Wright, M.J., Longstreth, W.T., Schumann, G., Grabe, H.J., Franke, B., Launer, L.J., Medland, S.E., Seshadri, S., Thompson, P.M., Ikram, M.A., Hibar, D.P., Adams, H.H.H., Jahanshad, N., Chauhan, G., Stein, J.L., Hofer, E., Renteria, M.E., Bis, J.C., Arias-Vasquez, A., Ikram, M.K., Desrivières, S., Vernooij, M.W., Abramovic, L., Alhusaini, S., Amin, N., Andersson, M., Arfanakis, K., Aribisala, B.S., Armstrong, N.J., Athanasiu, L., Axelsson, T., Beecham, A.H., Beiser, A., Bernard, M., Blanton, S.H., Bohlken, M.M., Boks, M.P., Bralten, J., Brickman, A.M., Carmichael, O., Chakravarty, M.M., Chen, Q., Ching, C.R.K., Chouraki, V., Cuellar-Partida, G., Crivello, F., den Braber, A., Doan, N.T., Ehrlich, S., Giddaluru, S., Goldman, A.L., Gottesman, R.F., Grimm, O., Griswold, M.E., Guadalupe, T., Gutman, B.A., Hass, J., Haukvik, U.K., Hoehn, D., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Jørgensen, K.N., Karbalai, N., Kasperaviciute, D., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Liewald, D.C.M., Lopez, L.M., Luciano, M., Macare, C., Marquand, A.F., Matarin, M., Mather, K.A., Mattheisen, M., McKay, D.R., Milaneschi, Y., Munoz Maniega, S., Nho, K., Nugent, A.C., Nyquist, P., Loohuis, L.M.O., Oosterlaan, J., Papmeyer, M., Pirpamer, L., Putz, B., Ramasamy, A., Richards, J.S., Risacher, S.L., Roiz-Santiañez, R., Rommelse, N., Ropele, S., Rose, E.J., Royle, N.A., Rundek, T., Sämann, P.G., Saremi, A., Satizabal, C.L., Schmaal, L., Schork, A.J., Shen, L., Shin, J., Shumskaya, E., Smith, A.V., Sprooten, E., Strike, L.T., Teumer, A., Tordesillas-Gutierrez, D., Toro, R., Trabzuni, D., Trompet, S., Vaidya, D., Van der Grond, J., van der Lee, S.J., van der Meer, D., van Donkelaar, M.M.J., van Eijk, K.R., Van Erp, T.G.M., Van Rooij, D., Walton, E., Westlye, L.T., Whelan, C.D., Windham, B.G., Winkler, A.M., Wittfeld, K., Woldehawariat, G., Wolf, C., Wolfers, T., Yanek, L.R., Yang, J., Zijdenbos, A., Zwiers, M.P., Agartz, I., Almasy, L., Ames, D., Amouyel, P., Andreassen, O.A., Arepalli, S., Assareh, A.A., Barral, S., Bastin, M.E., Becker, D.M., Becker, J.T., Bennett, D.A., Blangero, J., van Bokhoven, H., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bulayeva, K.B., Cahn, W., Calhoun, V.D., Cannon, D.M., Cavalleri, G.L., Cheng, C-Y, Cichon, S., Cookson, M.R., Corvin, A., Crespo-Facorro, B., Curran, J.E., Czisch, M., Dale, A.M., Davies, G.E., de Craen, A.J.M., de Geus, E.J.C., De Jager, P.L., de Zubicaray, G.I., Deary, I.J., Debette, S., DeCarli, C., Delanty, N., Depondt, C., DeStefano, A.L., Dillman, A., Djurovic, S., Donohoe, G., Drevets, W.C., Duggirala, R., Dyer, T.D., Enzinger, C., Erk, S., Espeseth, T., Fedko, I.O., Fernández, G., Ferrucci, L., Fisher, S.E., Fleischman, D.A., Ford, I., Fornage, M., Foroud, T.M., Fox, P.T., Francks, C., Fukunaga, M., Gibbs, J.R., Glahn, D.C., Gollub, R.L., Göring, H.H.H., Green, R.C., Gruber, O., Gudnason, V., Guelfi, S., Håberg, A.K., Hansell, N.K., Hardy, J., Hartman, C.A., Hashimoto, R., Hegenscheid, K., Heinz, A., Le Hellard, S., Hernandez, D.G., Heslenfeld, D.J., Ho, B-C., Hoekstra, P.J., Hoffmann, W., Hofman, A., Holsboer, F., Homuth, G., Hosten, N., Hottenga, J-J, Huentelman, M., Pol, H.E.H., Ikeda, M., Jack Jr, C.R., Jenkinson, M., Johnson, R., Jönsson, E.G., Jukema, J.W., Kahn, R.S., Kanai, R., Kloszewska, I., Knopman, D.S., Kochunov, P., Kwok, J.B., Lawrie, S.M., Lemaitre, H., Liu, X., Longo, D.L., Lopez, O.L., Lovestone, S., Martinez, O.P., Martinot, J-L, Mattay, V.S., McDonald, C., McIntosh, A.M., McMahon, F.J., McMahon, K.L., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Mohnke, S., Montgomery, G.W., Morris, D.W., Mosley, T.H., Mühleisen, T.W., Müller-Myhsok, B., Nalls, M.A., Nauck, M., Nichols, T.E., Niessen, W.J., Nöthen, M.M., Nyberg, L., Ohi, K., Olvera, R.L., Ophoff, R.A., Pandolfo, M., Paus, T., Pausova, Z., Penninx, B.W.J.H., Pike, G.B., Potkin, S.G., Psaty, B.M., Reppermund, S., Rietschel, M., Roffman, J.L., Romanczuk-Seiferth, N., Rotter, J.I., Ryten, M., Sacco, R.L., Sachdev, P.S., Saykin, A.J., Schmidt, R., Schmidt, H., Schofield, P.R., Sigursson, S., Simmons, A., Singleton, A., Sisodiya, S.M., Smith, C., Smoller, J.W., Soininen, H., Steen, V.M., Stott, D.J., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Tsolaki, M., Tzourio, C., Uitterlinden, A.G., Hernández, M.C.V., van der Brug, M., van der Lugt, A., van der Wee, N.J.A., van Haren, N.E.M., van ’t Ent, D., van Tol, M-J, Vardarajan, B.N., Vellas, B., Veltman, D.J., Volzke, H., Walter, H., Wardlaw, J.M., Wassink, T.H., Weale, M.E., Weinberger, D.R., Weiner, M.W., Wen, W., Westman, E., White, T., Wong, T.Y., Wright, C.B., Zielke, R.H., Zonderman, A.B., Martin, N.G., van Duijn, C.M., Wright, M.J., Longstreth, W.T., Schumann, G., Grabe, H.J., Franke, B., Launer, L.J., Medland, S.E., Seshadri, S., Thompson, P.M., and Ikram, M.A.

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

5. Novel genetic loci associated with hippocampal volume

Author

Hibar, DP, Adams, HHH, Jahanshad, N, Chauhan, G, Stein, JL, Hofer, E, Renteria, ME, Bis, JC, Arias-Vasquez, A, Ikram, MK, Desrivieres, S, Vernooij, MW, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beecham, AH, Beiser, A, Bernard, M, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chen, Q, Ching, CRK, Chouraki, V, Cuellar-Partida, G, Crivello, F, Den Braber, A, Nhat, TD, Ehrlich, S, Giddaluru, S, Goldman, AL, Gottesman, RF, Grimm, O, Griswold, ME, Guadalupe, T, Gutman, BA, Hass, J, Haukvik, UK, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Jorgensen, KN, Karbalai, N, Kasperaviciute, D, Kim, S, Klein, M, Kraemer, B, Lee, PH, Liewald, DCM, Lopez, LM, Luciano, M, Macare, C, Marquand, AF, Matarin, M, Mather, KA, Mattheisen, M, McKay, DR, Milaneschi, Y, Maniega, SM, Nho, K, Nugent, AC, Nyquist, P, Loohuis, LMO, Oosterlaan, J, Papmeyer, M, Pirpamer, L, Puetz, B, Ramasamy, A, Richards, JS, Risacher, SL, Roiz-Santianez, R, Rommelse, N, Ropele, S, Rose, EJ, Royle, NA, Rundek, T, Saemann, PG, Saremi, A, Satizabal, CL, Schmaal, L, Schork, AJ, Shen, L, Shin, J, Shumskaya, E, Smith, AV, Sprooten, E, Strike, LT, Teumer, A, Tordesillas-Gutierrez, D, Toro, R, Trabzuni, D, Trompet, S, Vaidya, D, Van der Grond, J, Van der Lee, SJ, Van der Meer, D, Van Donkelaar, MMJ, Van Eijk, KR, Van Erp, TGM, Van Rooij, D, Walton, E, Westlye, LT, Whelan, CD, Windham, BG, Winkler, AM, Wittfeld, K, Woldehawariat, G, Wolf, C, Wolfers, T, Yanek, LR, Yang, J, Zijdenbos, A, Zwiers, MP, Agartz, I, Almasy, L, Ames, D, Amouyel, P, Andreassen, OA, Arepalli, S, Assareh, AA, Barral, S, Bastin, ME, Becker, DM, Becker, JT, Bennett, DA, Blangero, J, van Bokhoven, H, Boomsma, DI, Brodaty, H, Brouwer, RM, Brunner, HG, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cahn, W, Calhoun, VD, Cannon, DM, Cavalleri, GL, Cheng, C-Y, Cichon, S, Cookson, MR, Corvin, A, Crespo-Facorro, B, Curran, JE, Czisch, M, Dale, AM, Davies, GE, De Craen, AJM, De Geus, EJC, De Jager, PL, De Zubicaray, GI, Deary, IJ, Debette, S, DeCarli, C, Delanty, N, Depondt, C, DeStefano, A, Dillman, A, Djurovic, S, Donohoe, G, Drevets, WC, Duggirala, R, Dyer, TD, Enzinger, C, Erk, S, Espeseth, T, Fedko, IO, Fernandez, G, Ferrucci, L, Fisher, SE, Fleischman, DA, Ford, I, Fornage, M, Foroud, TM, Fox, PT, Francks, C, Fukunaga, M, Gibbs, JR, Glahn, DC, Gollub, RL, Goring, HHH, Green, RC, Gruber, O, Gudnason, V, Guelfi, S, Haberg, AK, Hansell, NK, Hardy, J, Hartman, CA, Hashimoto, R, Hegenscheid, K, Heinz, A, Le Hellard, S, Hernandez, DG, Heslenfeld, DJ, Ho, B-C, Hoekstra, PJ, Hoffmann, W, Hofman, A, Holsboer, F, Homuth, G, Hosten, N, Hottenga, J-J, Huentelman, M, Pol, HEH, Ikeda, M, Jack, CR, Jenkinson, M, Johnson, R, Joensson, EG, Jukema, JW, Kahn, RS, Kanai, R, Kloszewska, I, Knopman, DS, Kochunov, P, Kwok, JB, Lawrie, SM, Lemaitre, H, Liu, X, Longo, DL, Lopez, OL, Lovestone, S, Martinez, O, Martinot, J-L, Mattay, VS, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Mecocci, P, Melle, I, Meyer-Lindenberg, A, Mohnke, S, Montgomery, GW, Morris, DW, Mosley, TH, Muhleisen, TW, Mueller-Myhsok, B, Nalls, MA, Nauck, M, Nichols, TE, Niessen, WJ, Nothen, MM, Nyberg, L, Ohi, K, Olvera, RL, Ophoff, RA, Pandolfo, M, Paus, T, Pausova, Z, Penninx, BWJH, Pike, GB, Potkin, SG, Psaty, BM, Reppermund, S, Rietschel, M, Roffman, JL, Romanczuk-Seiferth, N, Rotter, JI, Ryten, M, Sacco, RL, Sachdev, PS, Saykin, AJ, Schmidt, R, Schmidt, H, Schofield, PR, Sigursson, S, Simmons, A, Singleton, A, Sisodiya, SM, Smith, C, Smoller, JW, Soininen, H, Steen, VM, Stott, DJ, Sussmann, JE, Thalamuthu, A, Toga, AW, Traynor, BJ, Troncoso, J, Tsolaki, M, Tzourio, C, Uitterlinden, AG, Hernandez, MCV, Van der Brug, M, van der Lugt, A, van der Wee, NJA, Van Haren, NEM, van't Ent, D, Van Tol, M-J, Vardarajan, BN, Vellas, B, Veltman, DJ, Voelzke, H, Walter, H, Wardlaw, JM, Wassink, TH, Weale, ME, Weinberger, DR, Weiner, MW, Wen, W, Westman, E, White, T, Wong, TY, Wright, CB, Zielke, RH, Zonderman, AB, Martin, NG, Van Duijn, CM, Wright, MJ, Longstreth, WT, Schumann, G, Grabe, HJ, Franke, B, Launer, LJ, Medland, SE, Seshadri, S, Thompson, PM, Ikram, MA, Hibar, DP, Adams, HHH, Jahanshad, N, Chauhan, G, Stein, JL, Hofer, E, Renteria, ME, Bis, JC, Arias-Vasquez, A, Ikram, MK, Desrivieres, S, Vernooij, MW, Abramovic, L, Alhusaini, S, Amin, N, Andersson, M, Arfanakis, K, Aribisala, BS, Armstrong, NJ, Athanasiu, L, Axelsson, T, Beecham, AH, Beiser, A, Bernard, M, Blanton, SH, Bohlken, MM, Boks, MP, Bralten, J, Brickman, AM, Carmichael, O, Chakravarty, MM, Chen, Q, Ching, CRK, Chouraki, V, Cuellar-Partida, G, Crivello, F, Den Braber, A, Nhat, TD, Ehrlich, S, Giddaluru, S, Goldman, AL, Gottesman, RF, Grimm, O, Griswold, ME, Guadalupe, T, Gutman, BA, Hass, J, Haukvik, UK, Hoehn, D, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Jorgensen, KN, Karbalai, N, Kasperaviciute, D, Kim, S, Klein, M, Kraemer, B, Lee, PH, Liewald, DCM, Lopez, LM, Luciano, M, Macare, C, Marquand, AF, Matarin, M, Mather, KA, Mattheisen, M, McKay, DR, Milaneschi, Y, Maniega, SM, Nho, K, Nugent, AC, Nyquist, P, Loohuis, LMO, Oosterlaan, J, Papmeyer, M, Pirpamer, L, Puetz, B, Ramasamy, A, Richards, JS, Risacher, SL, Roiz-Santianez, R, Rommelse, N, Ropele, S, Rose, EJ, Royle, NA, Rundek, T, Saemann, PG, Saremi, A, Satizabal, CL, Schmaal, L, Schork, AJ, Shen, L, Shin, J, Shumskaya, E, Smith, AV, Sprooten, E, Strike, LT, Teumer, A, Tordesillas-Gutierrez, D, Toro, R, Trabzuni, D, Trompet, S, Vaidya, D, Van der Grond, J, Van der Lee, SJ, Van der Meer, D, Van Donkelaar, MMJ, Van Eijk, KR, Van Erp, TGM, Van Rooij, D, Walton, E, Westlye, LT, Whelan, CD, Windham, BG, Winkler, AM, Wittfeld, K, Woldehawariat, G, Wolf, C, Wolfers, T, Yanek, LR, Yang, J, Zijdenbos, A, Zwiers, MP, Agartz, I, Almasy, L, Ames, D, Amouyel, P, Andreassen, OA, Arepalli, S, Assareh, AA, Barral, S, Bastin, ME, Becker, DM, Becker, JT, Bennett, DA, Blangero, J, van Bokhoven, H, Boomsma, DI, Brodaty, H, Brouwer, RM, Brunner, HG, Buckner, RL, Buitelaar, JK, Bulayeva, KB, Cahn, W, Calhoun, VD, Cannon, DM, Cavalleri, GL, Cheng, C-Y, Cichon, S, Cookson, MR, Corvin, A, Crespo-Facorro, B, Curran, JE, Czisch, M, Dale, AM, Davies, GE, De Craen, AJM, De Geus, EJC, De Jager, PL, De Zubicaray, GI, Deary, IJ, Debette, S, DeCarli, C, Delanty, N, Depondt, C, DeStefano, A, Dillman, A, Djurovic, S, Donohoe, G, Drevets, WC, Duggirala, R, Dyer, TD, Enzinger, C, Erk, S, Espeseth, T, Fedko, IO, Fernandez, G, Ferrucci, L, Fisher, SE, Fleischman, DA, Ford, I, Fornage, M, Foroud, TM, Fox, PT, Francks, C, Fukunaga, M, Gibbs, JR, Glahn, DC, Gollub, RL, Goring, HHH, Green, RC, Gruber, O, Gudnason, V, Guelfi, S, Haberg, AK, Hansell, NK, Hardy, J, Hartman, CA, Hashimoto, R, Hegenscheid, K, Heinz, A, Le Hellard, S, Hernandez, DG, Heslenfeld, DJ, Ho, B-C, Hoekstra, PJ, Hoffmann, W, Hofman, A, Holsboer, F, Homuth, G, Hosten, N, Hottenga, J-J, Huentelman, M, Pol, HEH, Ikeda, M, Jack, CR, Jenkinson, M, Johnson, R, Joensson, EG, Jukema, JW, Kahn, RS, Kanai, R, Kloszewska, I, Knopman, DS, Kochunov, P, Kwok, JB, Lawrie, SM, Lemaitre, H, Liu, X, Longo, DL, Lopez, OL, Lovestone, S, Martinez, O, Martinot, J-L, Mattay, VS, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Mecocci, P, Melle, I, Meyer-Lindenberg, A, Mohnke, S, Montgomery, GW, Morris, DW, Mosley, TH, Muhleisen, TW, Mueller-Myhsok, B, Nalls, MA, Nauck, M, Nichols, TE, Niessen, WJ, Nothen, MM, Nyberg, L, Ohi, K, Olvera, RL, Ophoff, RA, Pandolfo, M, Paus, T, Pausova, Z, Penninx, BWJH, Pike, GB, Potkin, SG, Psaty, BM, Reppermund, S, Rietschel, M, Roffman, JL, Romanczuk-Seiferth, N, Rotter, JI, Ryten, M, Sacco, RL, Sachdev, PS, Saykin, AJ, Schmidt, R, Schmidt, H, Schofield, PR, Sigursson, S, Simmons, A, Singleton, A, Sisodiya, SM, Smith, C, Smoller, JW, Soininen, H, Steen, VM, Stott, DJ, Sussmann, JE, Thalamuthu, A, Toga, AW, Traynor, BJ, Troncoso, J, Tsolaki, M, Tzourio, C, Uitterlinden, AG, Hernandez, MCV, Van der Brug, M, van der Lugt, A, van der Wee, NJA, Van Haren, NEM, van't Ent, D, Van Tol, M-J, Vardarajan, BN, Vellas, B, Veltman, DJ, Voelzke, H, Walter, H, Wardlaw, JM, Wassink, TH, Weale, ME, Weinberger, DR, Weiner, MW, Wen, W, Westman, E, White, T, Wong, TY, Wright, CB, Zielke, RH, Zonderman, AB, Martin, NG, Van Duijn, CM, Wright, MJ, Longstreth, WT, Schumann, G, Grabe, HJ, Franke, B, Launer, LJ, Medland, SE, Seshadri, S, Thompson, PM, and Ikram, MA

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

6. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author

Pattaro, C, Teumer, A, Gorski, M, Chu, AY, Li, M, Mijatovic, V, Garnaas, M, Tin, A, Sorice, R, Li, Y, Taliun, D, Olden, M, Foster, M, Yang, Q, Chen, M-H, Pers, TH, Johnson, AD, Ko, Y-A, Fuchsberger, C, Tayo, B, Nalls, M, Feitosa, MF, Isaacs, A, Dehghan, A, d'Adamo, P, Adeyemo, A, Dieffenbach, AK, Zonderman, AB, Nolte, IM, van der Most, PJ, Wright, AF, Shuldiner, AR, Morrison, AC, Hofman, A, Smith, AV, Dreisbach, AW, Franke, A, Uitterlinden, AG, Metspalu, A, Tonjes, A, Lupo, A, Robino, A, Johansson, A, Demirkan, A, Kollerits, B, Freedman, BI, Ponte, B, Oostra, BA, Paulweber, B, Kraemer, BK, Mitchell, BD, Buckley, BM, Peralta, CA, Hayward, C, Helmer, C, Rotimi, CN, Shaffer, CM, Mueller, C, Sala, C, van Duijn, CM, Saint-Pierre, A, Ackermann, D, Shriner, D, Ruggiero, D, Toniolo, D, Lu, Y, Cusi, D, Czamara, D, Ellinghaus, D, Siscovick, DS, Ruderfer, D, Gieger, C, Grallert, H, Rochtchina, E, Atkinson, EJ, Holliday, EG, Boerwinkle, E, Salvi, E, Bottinger, EP, Murgia, F, Rivadeneira, F, Ernst, F, Kronenberg, F, Hu, FB, Navis, GJ, Curhan, GC, Ehret, GB, Homuth, G, Coassin, S, Thun, G-A, Pistis, G, Gambaro, G, Malerba, G, Montgomery, GW, Eiriksdottir, G, Jacobs, G, Li, G, Wichmann, H-E, Campbell, H, Schmidt, H, Wallaschofski, H, Voelzke, H, Brenner, H, Kroemer, HK, Kramer, H, Lin, H, Leach, IM, Ford, I, Guessous, I, Rudan, I, Prokopenko, I, Borecki, I, Heid, IM, Kolcic, I, Persico, I, Jukema, JW, Wilson, JF, Felix, JF, Divers, J, Lambert, J-C, Stafford, JM, Gaspoz, J-M, Smith, JA, Faul, JD, Wang, JJ, Ding, J, Hirschhorn, JN, Attia, J, Whitfield, JB, Chalmers, J, Viikari, J, Coresh, J, Denny, JC, Karjalainen, J, Fernandes, JK, Endlich, K, Butterbach, K, Keene, KL, Lohman, K, Portas, L, Launer, LJ, Lyytikaeinen, L-P, Yengo, L, Franke, L, Ferrucci, L, Rose, LM, Kedenko, L, Rao, M, Struchalin, M, Kleber, ME, Cavalieri, M, Haun, M, Cornelis, MC, Ciullo, M, Pirastu, M, de Andrade, M, McEvoy, MA, Woodward, M, Adam, M, Cocca, M, Nauck, M, Imboden, M, Waldenberger, M, Pruijm, M, Metzger, M, Stumvoll, M, Evans, MK, Sale, MM, Kaehoenen, M, Boban, M, Bochud, M, Rheinberger, M, Verweij, N, Bouatia-Naji, N, Martin, NG, Hastie, N, Probst-Hensch, N, Soranzo, N, Devuyst, O, Raitakari, O, Gottesman, O, Franco, OH, Polasek, O, Gasparini, P, Munroe, PB, Ridker, PM, Mitchell, P, Muntner, P, Meisinger, C, Smit, JH, Kovacs, P, Wild, PS, Froguel, P, Rettig, R, Maegi, R, Biffar, R, Schmidt, R, Middelberg, RPS, Carroll, RJ, Penninx, BW, Scott, RJ, Katz, R, Sedaghat, S, Wild, SH, Kardia, SLR, Ulivi, S, Hwang, S-J, Enroth, S, Kloiber, S, Trompet, S, Stengel, B, Hancock, SJ, Turner, ST, Rosas, SE, Stracke, S, Harris, TB, Zeller, T, Zemunik, T, Lehtimaeki, T, Illig, T, Aspelund, T, Nikopensius, T, Esko, T, Tanaka, T, Gyllensten, U, Voelker, U, Emilsson, V, Vitart, V, Aalto, V, Gudnason, V, Chouraki, V, Chen, W-M, Igl, W, Maerz, W, Koenig, W, Lieb, W, Loos, RJF, Liu, Y, Snieder, H, Pramstaller, PP, Parsa, A, O'Connell, JR, Susztak, K, Hamet, P, Tremblay, J, de Boer, IH, Boeger, CA, Goessling, W, Chasman, DI, Koettgen, A, Kao, WHL, Fox, CS, Pattaro, C, Teumer, A, Gorski, M, Chu, AY, Li, M, Mijatovic, V, Garnaas, M, Tin, A, Sorice, R, Li, Y, Taliun, D, Olden, M, Foster, M, Yang, Q, Chen, M-H, Pers, TH, Johnson, AD, Ko, Y-A, Fuchsberger, C, Tayo, B, Nalls, M, Feitosa, MF, Isaacs, A, Dehghan, A, d'Adamo, P, Adeyemo, A, Dieffenbach, AK, Zonderman, AB, Nolte, IM, van der Most, PJ, Wright, AF, Shuldiner, AR, Morrison, AC, Hofman, A, Smith, AV, Dreisbach, AW, Franke, A, Uitterlinden, AG, Metspalu, A, Tonjes, A, Lupo, A, Robino, A, Johansson, A, Demirkan, A, Kollerits, B, Freedman, BI, Ponte, B, Oostra, BA, Paulweber, B, Kraemer, BK, Mitchell, BD, Buckley, BM, Peralta, CA, Hayward, C, Helmer, C, Rotimi, CN, Shaffer, CM, Mueller, C, Sala, C, van Duijn, CM, Saint-Pierre, A, Ackermann, D, Shriner, D, Ruggiero, D, Toniolo, D, Lu, Y, Cusi, D, Czamara, D, Ellinghaus, D, Siscovick, DS, Ruderfer, D, Gieger, C, Grallert, H, Rochtchina, E, Atkinson, EJ, Holliday, EG, Boerwinkle, E, Salvi, E, Bottinger, EP, Murgia, F, Rivadeneira, F, Ernst, F, Kronenberg, F, Hu, FB, Navis, GJ, Curhan, GC, Ehret, GB, Homuth, G, Coassin, S, Thun, G-A, Pistis, G, Gambaro, G, Malerba, G, Montgomery, GW, Eiriksdottir, G, Jacobs, G, Li, G, Wichmann, H-E, Campbell, H, Schmidt, H, Wallaschofski, H, Voelzke, H, Brenner, H, Kroemer, HK, Kramer, H, Lin, H, Leach, IM, Ford, I, Guessous, I, Rudan, I, Prokopenko, I, Borecki, I, Heid, IM, Kolcic, I, Persico, I, Jukema, JW, Wilson, JF, Felix, JF, Divers, J, Lambert, J-C, Stafford, JM, Gaspoz, J-M, Smith, JA, Faul, JD, Wang, JJ, Ding, J, Hirschhorn, JN, Attia, J, Whitfield, JB, Chalmers, J, Viikari, J, Coresh, J, Denny, JC, Karjalainen, J, Fernandes, JK, Endlich, K, Butterbach, K, Keene, KL, Lohman, K, Portas, L, Launer, LJ, Lyytikaeinen, L-P, Yengo, L, Franke, L, Ferrucci, L, Rose, LM, Kedenko, L, Rao, M, Struchalin, M, Kleber, ME, Cavalieri, M, Haun, M, Cornelis, MC, Ciullo, M, Pirastu, M, de Andrade, M, McEvoy, MA, Woodward, M, Adam, M, Cocca, M, Nauck, M, Imboden, M, Waldenberger, M, Pruijm, M, Metzger, M, Stumvoll, M, Evans, MK, Sale, MM, Kaehoenen, M, Boban, M, Bochud, M, Rheinberger, M, Verweij, N, Bouatia-Naji, N, Martin, NG, Hastie, N, Probst-Hensch, N, Soranzo, N, Devuyst, O, Raitakari, O, Gottesman, O, Franco, OH, Polasek, O, Gasparini, P, Munroe, PB, Ridker, PM, Mitchell, P, Muntner, P, Meisinger, C, Smit, JH, Kovacs, P, Wild, PS, Froguel, P, Rettig, R, Maegi, R, Biffar, R, Schmidt, R, Middelberg, RPS, Carroll, RJ, Penninx, BW, Scott, RJ, Katz, R, Sedaghat, S, Wild, SH, Kardia, SLR, Ulivi, S, Hwang, S-J, Enroth, S, Kloiber, S, Trompet, S, Stengel, B, Hancock, SJ, Turner, ST, Rosas, SE, Stracke, S, Harris, TB, Zeller, T, Zemunik, T, Lehtimaeki, T, Illig, T, Aspelund, T, Nikopensius, T, Esko, T, Tanaka, T, Gyllensten, U, Voelker, U, Emilsson, V, Vitart, V, Aalto, V, Gudnason, V, Chouraki, V, Chen, W-M, Igl, W, Maerz, W, Koenig, W, Lieb, W, Loos, RJF, Liu, Y, Snieder, H, Pramstaller, PP, Parsa, A, O'Connell, JR, Susztak, K, Hamet, P, Tremblay, J, de Boer, IH, Boeger, CA, Goessling, W, Chasman, DI, Koettgen, A, Kao, WHL, and Fox, CS

Abstract

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Published
2016

7. Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene

Author

Ruiz, A., Heilmann, S., Harold, D., Gerrish, A., Sims, R., Sotolongo-Grau, O., Espinosa, A., Alegret, M., Arrieta, J. L., Lacour, A., Leber, M., Becker, J., Becker, T., Lafuente, A., Ruiz, S., Vargas, L., Rodríguez, O., Ortega, G., Dominguez, M-A, IGAP, Mayeux, R., Haines, J. L., Pericak-Vance, M. A., Hernández, I., Farrer, L. A., Schellenberg, G. D., Chouraki, V., Launer, L. J., van Duijn, C., Seshadri, S., Antúnez, C., Breteler, Monique, Serrano-Ríos, M., Jessen, F., Wagner, H., Tárraga, L., Nöthen, M. M., Maier, W., Boada, M., Ramírez, A., Thelen, M., Mauleón, A., Rosende-Roca, M., Bellenguez, C., Bis, J. C., Breteler, M. M., and Epidemiology

Subjects
SNP, thyroid receptor, Genomics, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, genetics [Alzheimer Disease], TRIP4 protein, human, genetics [Genetic Loci], Biology, Polymorphism, Single Nucleotide, molecular epidemiology, Cellular and Molecular Neuroscience, Alzheimer Disease, dementia risk, medicine, GWAS, Humans, Genetic Predisposition to Disease, ddc:610, Biological Psychiatry, Genetics, Odds ratio, DNA, genetics [Transcription Factors], medicine.disease, R1, Psychiatry and Mental health, Genetic Loci, Spain, Multiple comparisons problem, genetics [Polymorphism, Single Nucleotide], Original Article, Alzheimer's disease, Follow-Up Studies, Genome-Wide Association Study, Transcription Factors
Abstract

To follow-up loci discovered by the International Genomics of Alzheimer's Disease Project, we attempted independent replication of 19 single nucleotide polymorphisms (SNPs) in a large Spanish sample (Fundacio ACE data set; 1808 patients and 2564 controls). Our results corroborate association with four SNPs located in the genes INPP5D, MEF2C, ZCWPW1 and FERMT2, respectively. Of these, ZCWPW1 was the only SNP to withstand correction for multiple testing (P = 0.000655). Furthermore, we identify TRIP4 (rs74615166) as a novel genome-wide significant locus for Alzheimer's disease risk (odds ratio = 1.31; confidence interval 95% (1.19-1.44); P = 9.74 x 10(-9)).

Published
2014

8. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Author

Davies, G., Armstrong, N., Bis, J.C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C.A., Kirin, M., Lahti, J., van der Lee, S.J., Le Hellard, S., Liu, T., Marioni, R.E., Oldmeadow, C., Postmus, I., Smith, A.V., Smith, J.A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S.E., Hill, W.D., Liewald, D.C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A.A., Au, R., Becker, J.T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B.M., Campbell, H., Corley, J., De Jager, P.L., Dufouil, C., Eriksson, J.G., Espeseth, T., Faul, J.D., Ford, I., Scotland, Generation, Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Heiss, G., Hofman, A., Holliday, E.G., Huffman, J., Kardia, S.L.R, Kochan, N., Knopman, D.S., Kwok, J.B., Lambert, J-C, Lee, T., Li, G., Li, S-C, Loitfelder, M., Lopez, O.L., Lundervold, A.J., Lundqvist, A., Mather, K.A., Mirza, S.S., Nyberg, L., Oostra, B.A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B.M., Redmond, P., Reppermund, S., Rotter, J.I., Schmidt, H., Schuur, M., Schofield, P.W., Scott, R.J., Steen, V.M., Stott, D.J., van Swieten, J.C., Taylor, K.D., Trollor, J., Trompet, S., Uitterlinden, A.G., Weinstein, G., Widen, E., Windham, B.G., Jukema, J.W., Wright, A.F., Wright, M.J., Yang, Q., Amieva, H., Attia, J.R., Bennett, D.A, Brodaty, H., de Craen, A.J.M., Hayward, C., Ikram, M.A., Lindenberger, U., Nilsson, L-G, Porteous, D.J., Räikkönen, K., Reinvang, I., Rudan, I., Sachdev, P.S., Schmidt, R., Schofield, P.R., Srikanth, V., Starr, J.M., Turner, S.T., Weir, D.R., Wilson, J.F., van Duijn, C, Launer, L., Fitzpatrick, A.L., Seshadri, S., Mosley, T.H., Deary, I.J., Davies, G., Armstrong, N., Bis, J.C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C.A., Kirin, M., Lahti, J., van der Lee, S.J., Le Hellard, S., Liu, T., Marioni, R.E., Oldmeadow, C., Postmus, I., Smith, A.V., Smith, J.A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S.E., Hill, W.D., Liewald, D.C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A.A., Au, R., Becker, J.T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B.M., Campbell, H., Corley, J., De Jager, P.L., Dufouil, C., Eriksson, J.G., Espeseth, T., Faul, J.D., Ford, I., Scotland, Generation, Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Heiss, G., Hofman, A., Holliday, E.G., Huffman, J., Kardia, S.L.R, Kochan, N., Knopman, D.S., Kwok, J.B., Lambert, J-C, Lee, T., Li, G., Li, S-C, Loitfelder, M., Lopez, O.L., Lundervold, A.J., Lundqvist, A., Mather, K.A., Mirza, S.S., Nyberg, L., Oostra, B.A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B.M., Redmond, P., Reppermund, S., Rotter, J.I., Schmidt, H., Schuur, M., Schofield, P.W., Scott, R.J., Steen, V.M., Stott, D.J., van Swieten, J.C., Taylor, K.D., Trollor, J., Trompet, S., Uitterlinden, A.G., Weinstein, G., Widen, E., Windham, B.G., Jukema, J.W., Wright, A.F., Wright, M.J., Yang, Q., Amieva, H., Attia, J.R., Bennett, D.A, Brodaty, H., de Craen, A.J.M., Hayward, C., Ikram, M.A., Lindenberger, U., Nilsson, L-G, Porteous, D.J., Räikkönen, K., Reinvang, I., Rudan, I., Sachdev, P.S., Schmidt, R., Schofield, P.R., Srikanth, V., Starr, J.M., Turner, S.T., Weir, D.R., Wilson, J.F., van Duijn, C, Launer, L., Fitzpatrick, A.L., Seshadri, S., Mosley, T.H., and Deary, I.J.

Abstract

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

Published
2015

9. GWAS for executive function and processing speed suggests involvement of the CADM2 gene

Author

Ibrahim-Verbaas, C.A., Bressler, J., Debette, S., Schuur, M., Smith, A.V., Bis, J.C., Davies, G., Trompet, S., Smith, J.A., Wolf, C., Chibnik, L.B., Liu, Y., Vitart, V., Kirin, M., Petrovic, K., Polasek, O., Zgaga, L., Fawns-Ritchie, C., Hoffmann, P., Karjalainen, J., Lahti, J., Llewellyn, D.J., Schmidt, C.O., Mather, K.A., Chouraki, V., Sun, Q., Resnick, S.M., Rose, L.M., Oldmeadow, C., Stewart, M., Smith, B.H., Gudnason, V., Yang, Q., Mirza, S.S., Jukema, J.W., deJager, P.L., Harris, T.B., Liewald, D.C., Amin, N., Coker, L.H., Stegle, O., Lopez, O.L., Schmidt, R., Teumer, A., Ford, I., Karbalai, N., Becker, J.T., Jonsdottir, M.K., Au, R., Fehrmann, R.S.N., Herms, S., Nalls, M., Zhao, W., Turner, S.T., Yaffe, K., Lohman, K., van Swieten, J.C., Kardia, S.L.R, Knopman, D.S., Meeks, W.M., Heiss, G., Holliday, E.G., Schofield, P.W., Tanaka, T., Stott, D.J., Wang, J., Ridker, P., Gow, A.J., Pattie, A, Starr, J.M., Hocking, L.J., Armstrong, N.J., McLachlan, S., Shulman, J.M., Pilling, L.C., Eiriksdottir, G., Scott, R.J., Kochan, N.A., Palotie, A., Hsieh, Y-C, Eriksson, J.G., Penman, A., Gottesman, R.F., Oostra, B.A., Yu, L., DeStefano, A.L., Beiser, A., Garcia, M., Rotter, J.I., Nöthen, M.M., Hofman, A., Slagboom, P.E., Westendorp, R.G.J., Buckley, B.M., Wolf, P.A., Uitterlinden, A.G., Psaty, B.M., Grabe, H.J., Bandinelli, S., Chasman, D.I., Grodstein, F., Räikkönen, K., Lambert, J-C, Porteous, D.J., Price, J.F., Sachdev, P.S., Ferrucci, L., Attia, J.R., Rudan, I., Hayward, C., Wright, A.F., Wilson, J.F., Cichon, S., Franke, L., Schmidt, H., Ding, J., de Craen, A.J.M., Fornage, M., Bennett, D.A., Deary, I.J., Ikram, M.A., Launer, L.J., Fitzpatrick, A.L., Seshadri, S., van Duijn, C.M., Mosley, T.H., Ibrahim-Verbaas, C.A., Bressler, J., Debette, S., Schuur, M., Smith, A.V., Bis, J.C., Davies, G., Trompet, S., Smith, J.A., Wolf, C., Chibnik, L.B., Liu, Y., Vitart, V., Kirin, M., Petrovic, K., Polasek, O., Zgaga, L., Fawns-Ritchie, C., Hoffmann, P., Karjalainen, J., Lahti, J., Llewellyn, D.J., Schmidt, C.O., Mather, K.A., Chouraki, V., Sun, Q., Resnick, S.M., Rose, L.M., Oldmeadow, C., Stewart, M., Smith, B.H., Gudnason, V., Yang, Q., Mirza, S.S., Jukema, J.W., deJager, P.L., Harris, T.B., Liewald, D.C., Amin, N., Coker, L.H., Stegle, O., Lopez, O.L., Schmidt, R., Teumer, A., Ford, I., Karbalai, N., Becker, J.T., Jonsdottir, M.K., Au, R., Fehrmann, R.S.N., Herms, S., Nalls, M., Zhao, W., Turner, S.T., Yaffe, K., Lohman, K., van Swieten, J.C., Kardia, S.L.R, Knopman, D.S., Meeks, W.M., Heiss, G., Holliday, E.G., Schofield, P.W., Tanaka, T., Stott, D.J., Wang, J., Ridker, P., Gow, A.J., Pattie, A, Starr, J.M., Hocking, L.J., Armstrong, N.J., McLachlan, S., Shulman, J.M., Pilling, L.C., Eiriksdottir, G., Scott, R.J., Kochan, N.A., Palotie, A., Hsieh, Y-C, Eriksson, J.G., Penman, A., Gottesman, R.F., Oostra, B.A., Yu, L., DeStefano, A.L., Beiser, A., Garcia, M., Rotter, J.I., Nöthen, M.M., Hofman, A., Slagboom, P.E., Westendorp, R.G.J., Buckley, B.M., Wolf, P.A., Uitterlinden, A.G., Psaty, B.M., Grabe, H.J., Bandinelli, S., Chasman, D.I., Grodstein, F., Räikkönen, K., Lambert, J-C, Porteous, D.J., Price, J.F., Sachdev, P.S., Ferrucci, L., Attia, J.R., Rudan, I., Hayward, C., Wright, A.F., Wilson, J.F., Cichon, S., Franke, L., Schmidt, H., Ding, J., de Craen, A.J.M., Fornage, M., Bennett, D.A., Deary, I.J., Ikram, M.A., Launer, L.J., Fitzpatrick, A.L., Seshadri, S., van Duijn, C.M., and Mosley, T.H.

Abstract

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10-8) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10-9 after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10-4). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10-15), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10-11) and neuron cell-cell adhesion (P-value=1.48 × 10-13). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.Molecular Psychiatry advance online publication, 14 April 2015; doi:10.1038/mp.2015.37.

Published
2015

10. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

Author

Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J, Carrasquillo, M, Abraham, R, Hamshere, M, Pahwa, J, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, M, Brayne, C, Rubinsztein, D, Gill, M, Lawlor, B, Lynch, A, Brown, K, Passmore, P, Craig, D, Mcguinness, B, Todd, S, Holmes, C, Mann, D, Smith, A, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, P, Hooper, N, Vardy, E, Hardy, J, Mead, S, Fox, N, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, A, Kauwe, J, Cruchaga, C, Nowotny, P, Morris, J, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, P, Van Broeckhoven, C, Livingston, G, Bass, N, Gurling, H, Mcquillin, A, Gwilliam, R, Deloukas, P, Al Chalabi, A, Shaw, C, Tsolaki, M, Singleton, A, Guerreiro, R, Mühleisen, T, Nöthen, M, Moebus, S, Jöckel, K, Klopp, N, Wichmann, H, Pankratz, V, Sando, S, Aasly, J, Barcikowska, M, Wszolek, Z, Dickson, D, Graff Radford, N, Petersen, R, van Duijn, C, Breteler, M, Ikram, M, Destefano, A, Fitzpatrick, A, Lopez, O, Launer, L, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, T, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, Snædal, J, Björnsson, S, Jonsson, P, Chouraki, V, Genier Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, M, Pasquier, F, Mateo, I, Frank Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, P, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, S, Owen, M, O'Donovan, M, Amouyel, P, Williams, J, Carrasquillo, MM, Hamshere, ML, Pahwa, JS, Lupton, MK, Rubinsztein, DC, Brown, KS, Passmore, PA, McGuinness, B, Smith, AD, Kehoe, PG, Hooper, NM, Vardy, ERLC, Fox, NC, Goate, AM, Kauwe, JSK, Morris, JC, De Deyn, PP, Bass, NJ, McQuillin, A, Shaw, CE, Singleton, AB, Mühleisen, TW, Nöthen, MM, Pankratz, VS, Sando, SB, Aasly, JO, Wszolek, ZK, Dickson, DW, Graff Radford, NR, Petersen, RC, van Duijn, CM, Breteler, MMB, Ikram, MA, DeStefano, AL, Fitzpatrick, AL, Launer, LJ, Feulner, TM, Jonsson, PV, Bullido, MJ, ANNONI, GIORGIO, Holmans, PA, Younkin, SG, Owen, MJ, Williams, J., Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J, Carrasquillo, M, Abraham, R, Hamshere, M, Pahwa, J, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, M, Brayne, C, Rubinsztein, D, Gill, M, Lawlor, B, Lynch, A, Brown, K, Passmore, P, Craig, D, Mcguinness, B, Todd, S, Holmes, C, Mann, D, Smith, A, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, P, Hooper, N, Vardy, E, Hardy, J, Mead, S, Fox, N, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, A, Kauwe, J, Cruchaga, C, Nowotny, P, Morris, J, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, P, Van Broeckhoven, C, Livingston, G, Bass, N, Gurling, H, Mcquillin, A, Gwilliam, R, Deloukas, P, Al Chalabi, A, Shaw, C, Tsolaki, M, Singleton, A, Guerreiro, R, Mühleisen, T, Nöthen, M, Moebus, S, Jöckel, K, Klopp, N, Wichmann, H, Pankratz, V, Sando, S, Aasly, J, Barcikowska, M, Wszolek, Z, Dickson, D, Graff Radford, N, Petersen, R, van Duijn, C, Breteler, M, Ikram, M, Destefano, A, Fitzpatrick, A, Lopez, O, Launer, L, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, T, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, Snædal, J, Björnsson, S, Jonsson, P, Chouraki, V, Genier Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, M, Pasquier, F, Mateo, I, Frank Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, P, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, S, Owen, M, O'Donovan, M, Amouyel, P, Williams, J, Carrasquillo, MM, Hamshere, ML, Pahwa, JS, Lupton, MK, Rubinsztein, DC, Brown, KS, Passmore, PA, McGuinness, B, Smith, AD, Kehoe, PG, Hooper, NM, Vardy, ERLC, Fox, NC, Goate, AM, Kauwe, JSK, Morris, JC, De Deyn, PP, Bass, NJ, McQuillin, A, Shaw, CE, Singleton, AB, Mühleisen, TW, Nöthen, MM, Pankratz, VS, Sando, SB, Aasly, JO, Wszolek, ZK, Dickson, DW, Graff Radford, NR, Petersen, RC, van Duijn, CM, Breteler, MMB, Ikram, MA, DeStefano, AL, Fitzpatrick, AL, Launer, LJ, Feulner, TM, Jonsson, PV, Bullido, MJ, ANNONI, GIORGIO, Holmans, PA, Younkin, SG, Owen, MJ, and Williams, J.

Abstract

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ĝ‰Currency sign 1 × 10 -5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10 -17; including ADGC data, meta P = 5.0 × 10 -21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10 -14; including ADGC data, meta P = 1.2 × 10 -16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10 -4; including ADGC data, meta P = 8.6 × 10 -9), CD33 (GERAD+, P = 2.2 × 10 -4; including ADGC data, meta P = 1.6 × 10 -9) and EPHA1 (GERAD+, P = 3.4 × 10 -4; including ADGC data, meta P = 6.0 × 10 -10). © 2011 Nature America, Inc. All rights reserved.

Published
2011

11. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Author

Davies, G, Armstrong, N, Bis, J C, Bressler, J, Chouraki, V, Giddaluru, S, Hofer, E, Ibrahim-Verbaas, C A, Kirin, M, Lahti, J, van der Lee, S J, Le Hellard, S, Liu, T, Marioni, R E, Oldmeadow, C, Postmus, I, Smith, A V, Smith, J A, Thalamuthu, A, Thomson, R, Vitart, V, Wang, J, Yu, L, Zgaga, L, Zhao, W, Boxall, R, Harris, S E, Hill, W D, Liewald, D C, Luciano, M, Adams, H, Ames, D, Amin, N, Amouyel, P, Assareh, A A, Au, R, Becker, J T, Beiser, A, Berr, C, Bertram, L, Boerwinkle, E, Buckley, B M, Campbell, H, Corley, J, De Jager, P L, Dufouil, C, Eriksson, J G, Espeseth, T, Faul, J D, Ford, I, Scotland, Generation, Gottesman, R F, Griswold, M E, Gudnason, V, Harris, T B, Heiss, G, Hofman, A, Holliday, E G, Huffman, J, Kardia, S L R, Kochan, N, Knopman, D S, Kwok, J B, Lambert, J-C, Lee, T, Li, G, Li, S-C, Loitfelder, M, Lopez, O L, Lundervold, A J, Lundqvist, A, Mather, K A, Mirza, S S, Nyberg, L, Oostra, B A, Palotie, A, Papenberg, G, Pattie, A, Petrovic, K, Polasek, O, Psaty, B M, Redmond, P, Reppermund, S, Rotter, J I, Schmidt, H, Schuur, M, Schofield, P W, Scott, R J, Steen, V M, Stott, D J, van Swieten, J C, Taylor, K D, Trollor, J, Trompet, S, Uitterlinden, A G, Weinstein, G, Widen, E, Windham, B G, Jukema, J W, Wright, A F, Wright, M J, Yang, Q, Amieva, H, Attia, J R, Bennett, D A, Brodaty, H, de Craen, A J M, Hayward, C, Ikram, M A, Lindenberger, U, Nilsson, L-G, Porteous, D J, Räikkönen, K, Reinvang, I, Rudan, I, Sachdev, P S, Schmidt, R, Schofield, P R, Srikanth, V, Starr, J M, Turner, S T, Weir, D R, Wilson, J F, van Duijn, C, Launer, L, Fitzpatrick, A L, Seshadri, S, Mosley, T H, and Deary, I J

Abstract

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

Published
2015
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12. Meta-analysis of genetic association with diagnosed Alzheimer’s disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing

Author

Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Naj, AC, Boland, A, Vronskaya, M, Van Der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Aloso, R, Raybould, R, Chen, Y, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, L, Bacq, D, Denning, N, Jian, X, Zhao, Y, Zompo, MD, Fox, NC, Grove, ML, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Garcia, FS, Patel, Y, Brody, JA, Dombroski, B, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewics, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, W, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Pichler, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Fernadez, CM, Sussams, R, Lin, H, Fairchild, TJ, Benito, YA, Holmes, C, Comic, H, Frosch, MP, Thonberg, H, Maier, W, Roschupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernández, I, Kamboh, MI, Brundin, R, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth, WT, Montine, TJ, Frisardi, V, Ortega-Cubero, S, Rivadeneira, F, Petersen, RC, Deramecourt, V, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Caltagirone, C, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Uitterlinden, AG, Royall, DR, Dufouil, C, Maletta, RG, Moreno-Grau, S, Sano, M, Brice, A, Cecchetti, R, St George-Hyslop, P, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Baldwin, CT, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frölich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JI, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, Kauwe, JK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, C, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Cribbs, DH, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hüll, M, Geschwind, DH, Gilbert, Morris, J, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, G, Jin, LW, Leonenko, G, Jun, G, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jöckel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nöthen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, McKee, AC, Van Den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O’Bryant, S, Coto, E, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, W, Mead, S, Peskind, E, Rosser, M, Pierce, A, Ryan, N, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JF, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Bossù, P, Reisberg, B, Clarke, R, Reitz, C, and S, AD

Subjects
2 Aetiology, Aging, Prevention, Human Genome, 4202 Epidemiology, 42 Health Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, 3101 Biochemistry and Cell Biology, Alzheimer's Disease, 3105 Genetics, 3. Good health, Brain Disorders, Clinical Research, FOS: Biological sciences, Neurological, Acquired Cognitive Impairment, Genetics, 2.1 Biological and endogenous factors, Dementia, 31 Biological Sciences
Abstract

Introduction Late-onset Alzheimer’s disease (LOAD, onset age > 60 years) is the most prevalent dementia in the elderly 1 , and risk is partially driven by genetics 2 . Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS) 3–8 . To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 individuals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci ( IQCK , ACE , ADAM10 , and ADAMTS1 ). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants ( P = 1.32 × 10 −7 ) indicating that additional rare variants remain to be identified.

13. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

Author

P. Bosco, Rebecca Sims, Monique M.B. Breteler, L. Concari, Giuseppe Tosto, María J. Bullido, Kristel Sleegers, Fernando Valdivieso, Diana Zelenika, T. Feulner, Raffaele Ferri, Christophe Tzourio, P. Caffara, Davide Seripa, Benjamin Grenier-Boley, Paola Bossù, C. Chillotti, Marc Delepine, C. Deniz-Naranjo, Daniela Galimberti, David-Alexandre Trégouët, Benedetta Nacmias, Elisabeth M. C. Schrijvers, Karolien Bettens, Anne Boland, Christiane Reitz, Florentino Sanchez-Garcia, Dominique Campion, R. Rogers, C. Van Broeckhoven, Jean-Charles Lambert, Denise Harold, Amy Gerrish, Didier Hannequin, Mohammad Arfan Ikram, Michael Conlon O'Donovan, Elio Scarpini, Giorgio Annoni, Vincent Chouraki, Marc Lathrop, Francesco Panza, Chandra A. Reynolds, Gabriele Siciliano, Sandro Sorbi, Philippe Amouyel, Florence Pasquier, Luc Buée, Mikko Hiltunen, Claudine Berr, Eliecer Coto, Victoria Alvarez, Caroline Graff, Vincenzo Solfrizzi, Julie Williams, Jonathan A. Prince, Martin Ingelsson, Michael John Owen, Laura Fratiglioni, Jennifer Chapman, Ignacio Mateo, Annick Alpérovitch, H. Soininen, Michelangelo Mancuso, G. Spalletta, Matthias Riemenschneider, Andrea Pilotto, C. Van Cauwenberghe, Jacques Epelbaum, M. Del Zompo, Onofre Combarros, Lars Lannfelt, Yoichiro Kamatani, Beatrice Arosio, Jean-François Dartigues, Inserm U744, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Cardiff University, Bioinformatics, GlaxoSmithKline, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerpen, Belgium, Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium, University of Antwerp (UA), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Eastern Finland, G.H. Sergievsky Center, Columbia University, New York, NY, USA, Columbia University Irving Medical Center (CUIMC), Service of Neurology, University Hospital Marques de Valdecilla, University of Cantabria, Santander, Spain, Department of Psychiatry and Psychotherapy, Universitätsklinikum des Saarlandes, Universität des Saarlandes Saarbruecken, Germany, Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Centro Dino Ferrari [Milano], Università degli Studi di Milano = University of Milan (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Neuroscience, University of Parma, Parma, Italy, Università degli studi di Parma = University of Parma (UNIPR), Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central Asturias, Oviedo, Spain, Servicio de Inmunología. Hospital Unviersitario de Gran Canaria Dr Negrín. Bco, Las Palmas de Gran Canaria, Spain, Department of Geriatrics, Center for aging brain, Memory unit, University of Bari, Bari, Italy, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Department of neurological and psychiatric Sciences, University of Florence, Florence, Italy, Università degli Studi di Firenze = University of Florence (UniFI), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Clinical and Behavioral Neurology, IRCCS Fondazione Santa Lucia, Roma, Italy, Clinical and Behavioral Neurology - Neuroscienze e riabilitazione, IRCCS Fondazione Santa Lucia [Roma], Neurological clinic, University of Pisa, Pisa, Italy, University of Pisa - Università di Pisa, Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden, KI-Alzheimer's Disease Reseach Center, Department NVS, Karolinska Institutet, KIADRC, Stockholm, Sweden, IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina (EN), Italy, Department of Psychology [Riverside], University of California [Riverside] (UC Riverside), University of California (UC)-University of California (UC), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Uppsala University, Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden, Unit of Clinical Pharmacology, Teaching Hospital of Cagliari, Cagliari, Italy, Geriatric Unit & Gerontology-Geriatrics Research Laboratory, Department of Medical Sciences, I.R.C.C.S. 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Italy, Università degli Studi di Cagliari = University of Cagliari (UniCa), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, DZNE, Bonn, Germany, Génomique cardiovasculaire, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), This work was supported by the National Foundation for Alzheimer's disease and related disorders, the Institut Pasteur de Lille, the Centre National de Génotypage, Inserm, FRC (fondation sur la recherche sur le cerveau) and Rotary., EADI consortium, GERAD consortium, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Università degli Studi di Milano [Milano] (UNIMI)-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli studi di Bari Aldo Moro (UNIBA), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institut de psychiatrie et neurosciences (U894 / UMS 1266), University of California [Riverside] (UCR), University of California-University of California, Section of Clinical Pharmacology, Department of Neurosciences 'B.B. Brodie', University of Cagliari, Cagliari, Italy, Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Lambert, J, Grenier Boley, B, Harold, D, Zelenika, D, Chouraki, V, Kamatani, Y, Sleegers, K, Ikram, M, Hiltunen, M, Reitz, C, Mateo, I, Feulner, T, Bullido, M, Galimberti, D, Concari, L, Alvarez, V, Sims, R, Gerrish, A, Chapman, J, Deniz Naranjo, C, Solfrizzi, V, Sorbi, S, Arosio, B, Spalletta, G, Siciliano, G, Epelbaum, J, Hannequin, D, Dartigues, J, Tzourio, C, Berr, C, Schrijvers, E, Rogers, R, Tosto, G, Pasquier, F, Bettens, K, Van Cauwenberghe, C, Fratiglioni, L, Graff, C, Delepine, M, Ferri, R, Reynolds, C, Lannfelt, L, Ingelsson, M, Prince, J, Chillotti, C, Pilotto, A, Seripa, D, Boland, A, Mancuso, M, Bossù, P, Annoni, G, Nacmias, B, Bosco, P, Panza, F, Sanchez Garcia, F, Del Zompo, M, Coto, E, Owen, M, O'Donovan, M, Valdivieso, F, Caffara, P, Scarpini, E, Combarros, O, Buée, L, Campion, D, Soininen, H, Breteler, M, Riemenschneider, M, Van Broeckhoven, C, Alpérovitch, A, Lathrop, M, Trégouët, D, Williams, J, Amouyel, P, Epidemiology, Radiology & Nuclear Medicine, Neurology, Grenier-Boley, Benjamin, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé-Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre d'Etude du Polymorphisme Humain ( CEPH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ) -Fondation Jean Dausset, Departement of Epidemiology and Radiology, Erasmus MC, Rotterdam, Centro de Biologia Molecular Severo Ochoa (UAM-CSIC) and CIBERNED, Universidad Autonoma, Madrid, Spain, Università degli studi di Milano [Milano]-Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Internal Medicine, Geriatric Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy, University of Pisa [Pisa], Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Department of Epidemiology and Neurology, Erasmus MC, Rotterdam, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Aging Reasearch Center, Department NVS, Karolinska Institutet and Stockholm University, Stockholm, Sweden, University of California [Riverside] ( UCR ), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Department of Epidemiology, Erasmus MC, Rotterdam, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]

Subjects
Apolipoprotein E, haplotype, FERM domain-containing protein 4A, human, genetics [Alzheimer Disease], Genome-wide association study, Disease, Genome, Plasma, 0302 clinical medicine, genetics [Adaptor Proteins, Signal Transducing], blood [Amyloid beta-Peptides], GWAS, genetics [Genetic Predisposition to Disease], [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Genetics, 0303 health sciences, FRMD4A gene, amyloid, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, GWAS study, Alzheimer, FRMD4A, Alzheimer's disease, 3. Good health, Psychiatry and Mental health, Chemistry, genetics [Polymorphism, Single Nucleotide], Original Article, Corrigendum, medicine.medical_specialty, Amyloid, Single-nucleotide polymorphism, Locus (genetics), genome wide haplotype association study, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Cellular and Molecular Neuroscience, blood [Alzheimer Disease], Alzheimer Disease, genetics [Haplotypes], Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Psychiatry, Molecular Biology, plasma, Genetic association, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Amyloid beta-Peptides, business.industry, Haplotype, Case-control study, Haplotypes, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer’s disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n = 2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case– control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43–1.96); P= 1.11010). We finally searched for association between SNPs within the FRMD4A locus and Ab plasma concentrations in three independent non-demented populations (n = 2579). We reported that polymorphisms were associated with plasma Ab42/Ab40 ratio (best signal, P = 5.4107). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.

Published
2012

14. A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease.

Author

Huang KL, Marcora E, Pimenova AA, Di Narzo AF, Kapoor M, Jin SC, Harari O, Bertelsen S, Fairfax BP, Czajkowski J, Chouraki V, Grenier-Boley B, Bellenguez C, Deming Y, McKenzie A, Raj T, Renton AE, Budde J, Smith A, Fitzpatrick A, Bis JC, DeStefano A, Adams HHH, Ikram MA, van der Lee S, Del-Aguila JL, Fernandez MV, Ibañez L, Sims R, Escott-Price V, Mayeux R, Haines JL, Farrer LA, Pericak-Vance MA, Lambert JC, van Duijn C, Launer L, Seshadri S, Williams J, Amouyel P, Schellenberg GD, Zhang B, Borecki I, Kauwe JSK, Cruchaga C, Hao K, and Goate AM

Subjects
Alleles, Animals, Female, Humans, Linkage Disequilibrium genetics, Male, Mice, Risk Factors, Transcription Factors genetics, Alzheimer Disease genetics, Genetic Predisposition to Disease, Genome-Wide Association Study methods, Haplotypes genetics, Polymorphism, Single Nucleotide genetics, Proto-Oncogene Proteins genetics, Trans-Activators genetics
Abstract

A genome-wide survival analysis of 14,406 Alzheimer's disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and 14 novel loci associated with age at onset. Linkage disequilibrium score regression of 220 cell types implicated the regulation of myeloid gene expression in AD risk. The minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU.1, a transcription factor critical for myeloid cell development and function. AD heritability was enriched within the PU.1 cistrome, implicating a myeloid PU.1 target gene network in AD. Finally, experimentally altered PU.1 levels affected the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells. Our results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function.

Published
2017
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15. Corrigendum: 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

Author

Gorski M, Most PJV, Teumer A, Chu AY, Li M, Mijatovic V, Nolte IM, Cocca M, Taliun D, Gomez F, Li Y, Tayo B, Tin A, Feitosa MF, Aspelund T, Attia J, Biffar R, Bochud M, Boerwinkle E, Borecki I, Bottinger EP, Chen MH, Chouraki V, Ciullo M, Coresh J, Cornelis MC, Curhan GC, Adamo AP, Dehghan A, Dengler L, Ding J, Eiriksdottir G, Endlich K, Enroth S, Esko T, Franco OH, Gasparini P, Gieger C, Girotto G, Gottesman O, Gudnason V, Gyllensten U, Hancock SJ, Harris TB, Helmer C, Höllerer S, Hofer E, Hofman A, Holliday EG, Homuth G, Hu FB, Huth C, Hutri-Kähönen N, Hwang SJ, Imboden M, Johansson Å, Kähönen M, König W, Kramer H, Krämer BK, Kumar A, Kutalik Z, Lambert JC, Launer LJ, Lehtimäki T, de Borst MH, Navis G, Swertz M, Liu Y, Lohman K, Loos RJF, Lu Y, Lyytikäinen LP, McEvoy MA, Meisinger C, Meitinger T, Metspalu A, Metzger M, Mihailov E, Mitchell P, Nauck M, Oldehinkel AJ, Olden M, Wjh Penninx B, Pistis G, Pramstaller PP, Probst-Hensch N, Raitakari OT, Rettig R, Ridker PM, Rivadeneira F, Robino A, Rosas SE, Ruderfer D, Ruggiero D, Saba Y, Sala C, Schmidt H, Schmidt R, Scott RJ, Sedaghat S, Smith AV, Sorice R, Stengel B, Stracke S, Strauch K, Toniolo D, Uitterlinden AG, Ulivi S, Viikari JS, Völker U, Vollenweider P, Völzke H, Vuckovic D, Waldenberger M, Wang JJ, Yang Q, Chasman DI, Tromp G, Snieder H, Heid IM, Fox CS, Köttgen A, Pattaro C, Böger CA, and Fuchsberger C

Abstract

This corrects the article DOI: 10.1038/srep45040.

Published
2017
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16. 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

Author

Gorski M, van der Most PJ, Teumer A, Chu AY, Li M, Mijatovic V, Nolte IM, Cocca M, Taliun D, Gomez F, Li Y, Tayo B, Tin A, Feitosa MF, Aspelund T, Attia J, Biffar R, Bochud M, Boerwinkle E, Borecki I, Bottinger EP, Chen MH, Chouraki V, Ciullo M, Coresh J, Cornelis MC, Curhan GC, d'Adamo AP, Dehghan A, Dengler L, Ding J, Eiriksdottir G, Endlich K, Enroth S, Esko T, Franco OH, Gasparini P, Gieger C, Girotto G, Gottesman O, Gudnason V, Gyllensten U, Hancock SJ, Harris TB, Helmer C, Höllerer S, Hofer E, Hofman A, Holliday EG, Homuth G, Hu FB, Huth C, Hutri-Kähönen N, Hwang SJ, Imboden M, Johansson Å, Kähönen M, König W, Kramer H, Krämer BK, Kumar A, Kutalik Z, Lambert JC, Launer LJ, Lehtimäki T, de Borst M, Navis G, Swertz M, Liu Y, Lohman K, Loos RJF, Lu Y, Lyytikäinen LP, McEvoy MA, Meisinger C, Meitinger T, Metspalu A, Metzger M, Mihailov E, Mitchell P, Nauck M, Oldehinkel AJ, Olden M, Wjh Penninx B, Pistis G, Pramstaller PP, Probst-Hensch N, Raitakari OT, Rettig R, Ridker PM, Rivadeneira F, Robino A, Rosas SE, Ruderfer D, Ruggiero D, Saba Y, Sala C, Schmidt H, Schmidt R, Scott RJ, Sedaghat S, Smith AV, Sorice R, Stengel B, Stracke S, Strauch K, Toniolo D, Uitterlinden AG, Ulivi S, Viikari JS, Völker U, Vollenweider P, Völzke H, Vuckovic D, Waldenberger M, Jin Wang J, Yang Q, Chasman DI, Tromp G, Snieder H, Heid IM, Fox CS, Köttgen A, Pattaro C, Böger CA, and Fuchsberger C

Subjects
Gene Frequency, Genome, Human, Genome-Wide Association Study, Genotyping Techniques, Humans, Polymorphism, Single Nucleotide, Computational Biology methods, Genetic Loci, Kidney physiology
Abstract

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10 -8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.

Published
2017
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17. Novel genetic loci underlying human intracranial volume identified through genome-wide association.

Author

Adams HH, Hibar DP, Chouraki V, Stein JL, Nyquist PA, Rentería ME, Trompet S, Arias-Vasquez A, Seshadri S, Desrivières S, Beecham AH, Jahanshad N, Wittfeld K, Van der Lee SJ, Abramovic L, Alhusaini S, Amin N, Andersson M, Arfanakis K, Aribisala BS, Armstrong NJ, Athanasiu L, Axelsson T, Beiser A, Bernard M, Bis JC, Blanken LM, Blanton SH, Bohlken MM, Boks MP, Bralten J, Brickman AM, Carmichael O, Chakravarty MM, Chauhan G, Chen Q, Ching CR, Cuellar-Partida G, Braber AD, Doan NT, Ehrlich S, Filippi I, Ge T, Giddaluru S, Goldman AL, Gottesman RF, Greven CU, Grimm O, Griswold ME, Guadalupe T, Hass J, Haukvik UK, Hilal S, Hofer E, Hoehn D, Holmes AJ, Hoogman M, Janowitz D, Jia T, Kasperaviciute D, Kim S, Klein M, Kraemer B, Lee PH, Liao J, Liewald DC, Lopez LM, Luciano M, Macare C, Marquand A, Matarin M, Mather KA, Mattheisen M, Mazoyer B, McKay DR, McWhirter R, Milaneschi Y, Mirza-Schreiber N, Muetzel RL, Maniega SM, Nho K, Nugent AC, Loohuis LM, Oosterlaan J, Papmeyer M, Pappa I, Pirpamer L, Pudas S, Pütz B, Rajan KB, Ramasamy A, Richards JS, Risacher SL, Roiz-Santiañez R, Rommelse N, Rose EJ, Royle NA, Rundek T, Sämann PG, Satizabal CL, Schmaal L, Schork AJ, Shen L, Shin J, Shumskaya E, Smith AV, Sprooten E, Strike LT, Teumer A, Thomson R, Tordesillas-Gutierrez D, Toro R, Trabzuni D, Vaidya D, Van der Grond J, Van der Meer D, Van Donkelaar MM, Van Eijk KR, Van Erp TG, Van Rooij D, Walton E, Westlye LT, Whelan CD, Windham BG, Winkler AM, Woldehawariat G, Wolf C, Wolfers T, Xu B, Yanek LR, Yang J, Zijdenbos A, Zwiers MP, Agartz I, Aggarwal NT, Almasy L, Ames D, Amouyel P, Andreassen OA, Arepalli S, Assareh AA, Barral S, Bastin ME, Becker DM, Becker JT, Bennett DA, Blangero J, van Bokhoven H, Boomsma DI, Brodaty H, Brouwer RM, Brunner HG, Buckner RL, Buitelaar JK, Bulayeva KB, Cahn W, Calhoun VD, Cannon DM, Cavalleri GL, Chen C, Cheng CY, Cichon S, Cookson MR, Corvin A, Crespo-Facorro B, Curran JE, Czisch M, Dale AM, Davies GE, De Geus EJ, De Jager PL, de Zubicaray GI, Delanty N, Depondt C, DeStefano AL, Dillman A, Djurovic S, Donohoe G, Drevets WC, Duggirala R, Dyer TD, Erk S, Espeseth T, Evans DA, Fedko IO, Fernández G, Ferrucci L, Fisher SE, Fleischman DA, Ford I, Foroud TM, Fox PT, Francks C, Fukunaga M, Gibbs JR, Glahn DC, Gollub RL, Göring HH, Grabe HJ, Green RC, Gruber O, Gudnason V, Guelfi S, Hansell NK, Hardy J, Hartman CA, Hashimoto R, Hegenscheid K, Heinz A, Le Hellard S, Hernandez DG, Heslenfeld DJ, Ho BC, Hoekstra PJ, Hoffmann W, Hofman A, Holsboer F, Homuth G, Hosten N, Hottenga JJ, Hulshoff Pol HE, Ikeda M, Ikram MK, Jack CR Jr, Jenkinson M, Johnson R, Jönsson EG, Jukema JW, Kahn RS, Kanai R, Kloszewska I, Knopman DS, Kochunov P, Kwok JB, Lawrie SM, Lemaître H, Liu X, Longo DL, Longstreth WT Jr, Lopez OL, Lovestone S, Martinez O, Martinot JL, Mattay VS, McDonald C, McIntosh AM, McMahon KL, McMahon FJ, Mecocci P, Melle I, Meyer-Lindenberg A, Mohnke S, Montgomery GW, Morris DW, Mosley TH, Mühleisen TW, Müller-Myhsok B, Nalls MA, Nauck M, Nichols TE, Niessen WJ, Nöthen MM, Nyberg L, Ohi K, Olvera RL, Ophoff RA, Pandolfo M, Paus T, Pausova Z, Penninx BW, Pike GB, Potkin SG, Psaty BM, Reppermund S, Rietschel M, Roffman JL, Romanczuk-Seiferth N, Rotter JI, Ryten M, Sacco RL, Sachdev PS, Saykin AJ, Schmidt R, Schofield PR, Sigurdsson S, Simmons A, Singleton A, Sisodiya SM, Smith C, Smoller JW, Soininen H, Srikanth V, Steen VM, Stott DJ, Sussmann JE, Thalamuthu A, Tiemeier H, Toga AW, Traynor BJ, Troncoso J, Turner JA, Tzourio C, Uitterlinden AG, Hernández MC, Van der Brug M, Van der Lugt A, Van der Wee NJ, Van Duijn CM, Van Haren NE, Van T Ent D, Van Tol MJ, Vardarajan BN, Veltman DJ, Vernooij MW, Völzke H, Walter H, Wardlaw JM, Wassink TH, Weale ME, Weinberger DR, Weiner MW, Wen W, Westman E, White T, Wong TY, Wright CB, Zielke HR, Zonderman AB, Deary IJ, DeCarli C, Schmidt H, Martin NG, De Craen AJ, Wright MJ, Launer LJ, Schumann G, Fornage M, Franke B, Debette S, Medland SE, Ikram MA, and Thompson PM

Subjects
Brain growth & development, Brain pathology, Genetic Loci genetics, Humans, Oncogene Protein v-akt genetics, Parkinson Disease genetics, Phenotype, Phosphatidylinositol 3-Kinases genetics, White People, Cognition physiology, Genetic Predisposition to Disease, Genome-Wide Association Study methods, Polymorphism, Single Nucleotide genetics
Abstract

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

Published
2016
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18. PLD3 variants in population studies.

Author

van der Lee SJ, Holstege H, Wong TH, Jakobsdottir J, Bis JC, Chouraki V, van Rooij JG, Grove ML, Smith AV, Amin N, Choi SH, Beiser AS, Garcia ME, van IJcken WF, Pijnenburg YA, Louwersheimer E, Brouwer RW, van den Hout MC, Oole E, Eirkisdottir G, Levy D, Rotter JI, Emilsson V, O'Donnell CJ, Aspelund T, Uitterlinden AG, Launer LJ, Hofman A, Boerwinkle E, Psaty BM, DeStefano AL, Scheltens P, Seshadri S, van Swieten JC, Gudnason V, van der Flier WM, Ikram MA, and van Duijn CM

Subjects
Female, Humans, Male, Alzheimer Disease genetics, Genetic Predisposition to Disease genetics, Genetic Variation genetics, Phospholipase D genetics
Published
2015
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