Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

TitleRare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2017
AuthorsSims, R, van der Lee, SJ, Naj, AC, Bellenguez, C, Badarinarayan, N, Jakobsdottir, J, Kunkle, BW, Boland, A, Raybould, R, Bis, JC, Martin, ER, Grenier-Boley, B, Heilmann-Heimbach, S, Chouraki, V, Kuzma, AB, Sleegers, K, Vronskaya, M, Ruiz, A, Graham, RR, Olaso, R, Hoffmann, P, Grove, ML, Vardarajan, BN, Hiltunen, M, Nöthen, MM, White, CC, Hamilton-Nelson, KL, Epelbaum, J, Maier, W, Choi, S-H, Beecham, GW, Dulary, C, Herms, S, Smith, AV, Funk, CC, Derbois, C, Forstner, AJ, Ahmad, S, Li, H, Bacq, D, Harold, D, Satizabal, CL, Valladares, O, Squassina, A, Thomas, R, Brody, JA, Qu, L, Sánchez-Juan, P, Morgan, T, Wolters, FJ, Zhao, Y, Garcia, FSanchez, Denning, N, Fornage, M, Malamon, J, Naranjo, MCandida De, Majounie, E, Mosley, TH, Dombroski, B, Wallon, D, Lupton, MK, Dupuis, J, Whitehead, P, Fratiglioni, L, Medway, C, Jian, X, Mukherjee, S, Keller, L, Brown, K, Lin, H, Cantwell, LB, Panza, F, McGuinness, B, Moreno-Grau, S, Burgess, JD, Solfrizzi, V, Proitsi, P, Adams, HH, Allen, M, Seripa, D, Pastor, P, L Cupples, A, Price, ND, Hannequin, D, Frank-García, A, Levy, D, Chakrabarty, P, Caffarra, P, Giegling, I, Beiser, AS, Giedraitis, V, Hampel, H, Garcia, ME, Wang, X, Lannfelt, L, Mecocci, P, Eiriksdottir, G, Crane, PK, Pasquier, F, Boccardi, V, Henández, I, Barber, RC, Scherer, M, Tarraga, L, Adams, PM, Leber, M, Chen, Y, Albert, MS, Riedel-Heller, S, Emilsson, V, Beekly, D, Braae, A, Schmidt, R, Blacker, D, Masullo, C, Schmidt, H, Doody, RS, Spalletta, G, Jr, WTLongstre, Fairchild, TJ, Bossù, P, Lopez, OL, Frosch, MP, Sacchinelli, E, Ghetti, B, Yang, Q, Huebinger, RM, Jessen, F, Li, S, M Kamboh, I, Morris, J, Sotolongo-Grau, O, Katz, MJ, Corcoran, C, Dunstan, M, Braddel, A, Thomas, C, Meggy, A, Marshall, R, Gerrish, A, Chapman, J, Aguilar, M, Taylor, S, Hill, M, Fairén, MDíez, Hodges, A, Vellas, B, Soininen, H, Kloszewska, I, Daniilidou, M, Uphill, J, Patel, Y, Hughes, JT, Lord, J, Turton, J, Hartmann, AM, Cecchetti, R, Fenoglio, C, Serpente, M, Arcaro, M, Caltagirone, C, Orfei, MDonata, Ciaramella, A, Pichler, S, Mayhaus, M, Gu, W, Lleo, A, Fortea, J, Blesa, R, Barber, IS, Brookes, K, Cupidi, C, Maletta, RGiovanni, Carrell, D, Sorbi, S, Moebus, S, Urbano, M, Pilotto, A, Kornhuber, J, Bosco, P, Todd, S, Craig, D, Johnston, J, Gill, M, Lawlor, B, Lynch, A, Fox, NC, Hardy, J, Albin, RL, Apostolova, LG, Arnold, SE, Asthana, S, Atwood, CS, Baldwin, CT, Barnes, LL, Barral, S, Beach, TG, Becker, JT, Bigio, EH, Bird, TD, Boeve, BF, Bowen, JD, Boxer, A, Burke, JR, Burns, JM, Buxbaum, JD, Cairns, NJ, Cao, C, Carlson, CS, Carlsson, CM, Carney, RM, Carrasquillo, MM, Carroll, SL, Diaz, CCeballos, Chui, HC, Clark, DG, Cribbs, DH, Crocco, EA, DeCarli, C, Dick, M, Duara, R, Evans, DA, Faber, KM, Fallon, KB, Fardo, DW, Farlow, MR, Ferris, S, Foroud, TM, Galasko, DR, Gearing, M, Geschwind, DH, Gilbert, JR, Graff-Radford, NR, Green, RC, Growdon, JH, Hamilton, RL, Harrell, LE, Honig, LS, Huentelman, MJ, Hulette, CM, Hyman, BT, Jarvik, GP, Abner, E, Jin, L-W, Jun, G, Karydas, A, Kaye, JA, Kim, R, Kowall, NW, Kramer, JH, LaFerla, FM, Lah, JJ, Leverenz, JB, Levey, AI, Li, G, Lieberman, AP, Lunetta, KL, Lyketsos, CG, Marson, DC, Martiniuk, F, Mash, DC, Masliah, E, McCormick, WC, McCurry, SM, McDavid, AN, McKee, AC, Mesulam, M, Miller, BL, Miller, CA, Miller, JW, Morris, JC, Murrell, JR, Myers, AJ, O'Bryant, S, Olichney, JM, Pankratz, VS, Parisi, JE, Paulson, HL, Perry, W, Peskind, E, Pierce, A, Poon, WW, Potter, H, Quinn, JF, Raj, A, Raskind, M, Reisberg, B, Reitz, C, Ringman, JM, Roberson, ED, Rogaeva, E, Rosen, HJ, Rosenberg, RN, Sager, MA, Saykin, AJ, Schneider, JA, Schneider, LS, Seeley, WW, Smith, AG, Sonnen, JA, Spina, S, Stern, RA, Swerdlow, RH, Tanzi, RE, Thornton-Wells, TA, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Van Eldik, LJ, Vinters, HV, Vonsattel, JPaul, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, Woltjer, RL, Wright, CB, Yu, C-E, Yu, L, Garzia, F, Golamaully, F, Septier, G, Engelborghs, S, Vandenberghe, R, De Deyn, PP, Fernadez, CMuñoz, Benito, YAladro, Thonberg, H, Forsell, C, Lilius, L, Kinhult-Stählbom, A, Kilander, L, Brundin, RM, Concari, L, Helisalmi, S, Koivisto, AMaria, Haapasalo, A, Dermecourt, V, Fiévet, N, Hanon, O, Dufouil, C, Brice, A, Ritchie, K, Dubois, B, Himali, JJ, C Keene, D, Tschanz, JA, Fitzpatrick, AL, Kukull, WA, Norton, M, Aspelund, T, Larson, EB, Munger, R, Rotter, JI, Lipton, RB, Bullido, MJ, Hofman, A, Montine, TJ, Coto, E, Boerwinkle, E, Petersen, RC, Alvarez, V, Rivadeneira, F, Reiman, EM, Gallo, M, O'Donnell, CJ, Reisch, JS, Bruni, ACecilia, Royall, DR, Dichgans, M, Sano, M, Galimberti, D, St George-Hyslop, P, Scarpini, E, Tsuang, DW, Mancuso, M, Bonuccelli, U, Winslow, AR, Daniele, A, Wu, C-K, Peters, O, Nacmias, B, Riemenschneider, M, Heun, R, Brayne, C, Rubinsztein, DC, Bras, J, Guerreiro, R, Al-Chalabi, A, Shaw, CE, Collinge, J, Mann, D, Tsolaki, M, Clarimon, J, Sussams, R, Lovestone, S, O'Donovan, MC, Owen, MJ, Behrens, TW, Mead, S, Goate, AM, Uitterlinden, AG, Holmes, C, Cruchaga, C, Ingelsson, M, Bennett, DA, Powell, J, Golde, TE, Graff, C, De Jager, PL, Morgan, K, Ertekin-Taner, N, Combarros, O, Psaty, BM, Passmore, P, Younkin, SG, Berr, C, Gudnason, V, Rujescu, D, Dickson, DW, Dartigues, J-F, DeStefano, AL, Ortega-Cubero, S, Hakonarson, H, Campion, D, Boada, M, Kauwe, JKeoni, Farrer, LA, Van Broeckhoven, C, M Ikram, A, Jones, L, Haines, JL, Tzourio, C, Launer, LJ, Escott-Price, V, Mayeux, R, Deleuze, J-F, Amin, N, Holmans, PA, Pericak-Vance, MA, Amouyel, P, van Duijn, CM, Ramirez, A, San Wang, L-, Lambert, J-C, Seshadri, S, Williams, J, Schellenberg, GD
Corporate AuthorsARUK Consortium, GERAD/PERADES, CHARGE, ADGC, EADI
JournalNat Genet
Volume49
Issue9
Pagination1373-1384
Date Published2017 Sep
ISSN1546-1718
KeywordsAdaptor Proteins, Signal Transducing, Alzheimer Disease, Amino Acid Sequence, Case-Control Studies, Exome, Gene Expression Profiling, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Immunity, Innate, Linkage Disequilibrium, Membrane Glycoproteins, Microglia, Odds Ratio, Phospholipase C gamma, Polymorphism, Single Nucleotide, Protein Interaction Maps, Receptors, Immunologic, Sequence Homology, Amino Acid
Abstract

We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P

DOI10.1038/ng.3916
Alternate JournalNat. Genet.
PubMed ID28714976
PubMed Central IDPMC5669039
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P50 MH060451 / MH / NIMH NIH HHS / United States
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