Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
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 < 1 x 10(-4)) in 35,962 independent samples using de nov...
| Autores: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Tipo de documento: | Artículo |
| Estado: | Published version |
| Fecha de publicación: | 2017 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p14146 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14146 https://europepmc.org/articles/pmc5669039 |
| Nivel de acceso: | Acceso abierto |
| _version_ | 1878739729098211328 |
|---|---|
| author | Sims, R |
| author2 | 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 Nothen, MM White, CC Hamilton-Nelson, KL Epelbaum, J Maier, W Choi, SH Beecham, GW Dulary, C Herms, S Smith, AV Funk, CC Derbois, C Forstner, AJ Ahmad, S Li, HD Bacq, D Harold, D Satizabal, CL Valladares, O Squassina, A Thomas, R Brody, JA Qu, LM Sanchez-Juan, P Morgan, T Wolters, FJ Zhao, Y Garcia, FS Denning, N Fornage, M Malamon, J Naranjo, MCD Majounie, E Mosley, TH Dombroski, B Wallon, D Lupton, MK Dupuis, J Whitehead, P Fratiglioni, L Medway, C Jian, XQ Mukherjee, S Keller, L Brown, K Lin, HH Cantwell, LB Panza, F McGuinness, B Moreno-Grau, S Burgess, JD Solfrizzi, V Proitsi, P Adams, HH Allen, M Seripa, D Pastor, P Cupples, LA Price, ND Hannequin, D Frank-Garcia, 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 Henandez, 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 Longstreth, WT Fairchild, TJ Bossu, P Lopez, OL Frosch, MP Sacchinelli, E Ghetti, B Yang, Q Huebinger, RM Jessen, F Li, S Kamboh, MI 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 Fairen, MD 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, MD Ciaramella, A Pichler, S Mayhaus, M Gu, W Lleo, A Forte, J Blesa, R Barber, IS Brookes, K Cupidi, C Maletta, RG 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, CH Carlson, CS Carlsson, CM Carney, RM Carrasquillo, MM Carroll, SL Diaz, CC 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, LW 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 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, JP Weintraub, S Welsh-Bohmer, KA Wilhelmsen, KC Williamson, J Woltjer, RL Wright, CB Yu, CE Yu, L Garzia, F Golamaully, F Septier, G Engelborghs, S Vandenberghe, R De Deyn, PP Fernadez, CM Benito, YA Thonberg, H Forsell, C Lilius, L Kinhult-Stahlbom, A Kilander, L Brundin, R Concari, L Helisalmi, S Koivisto, AM Haapasalo, A Dermecourt, V Fievet, N Hanon, O Dufouil, C Brice, A Ritchie, K Dubois, B Himali, JJ Keene, CD Tschanz, J 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, AC 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, CK 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, JF DeStefano, AL Ortega-Cubero, S Hakonarson, H Campion, D Boada, M Kauwe, JK Farrer, LA Van Broeckhoven, C Ikram, MA Jones, L Haines, JL Tzourio, C Launer, LJ Escott-Price, V Mayeux-, R Deleuze, JF Amin, N Holmans, PA Pericak-Vance, MA Amouyel, P van Duijn, CM Ramirez, A Wang, LS Lambert, JC Seshadri, S Williams, J Schellenberg, GD |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| author_browse | Abner, E Adams, HH Adams, PM Aguilar, M Ahmad, S Al-Chalabi, A Albert, MS Albin, RL Allen, M Alvarez, V Amin, N Amouyel, P Apostolova, LG Arcaro, M Arnold, SE Aspelund, T Asthana, S Atwood, CS Bacq, D Badarinarayan, N Baldwin, CT Barber, IS Barber, RC Barnes, LL Barral, S Beach, TG Becker, JT Beecham, GW Beekly, D Behrens, TW Beiser, AS Bellenguez, C Benito, YA Bennett, DA Berr, C Bigio, EH Bird, TD Bis, JC Blacker, D Blesa, R Boada, M Boccardi, V Boerwinkle, E Boeve, BF Boland, A Bonuccelli, U Bosco, P Bossu, P Bowen, JD Boxer, A Braae, A Braddel, A Bras, J Brayne, C Brice, A Brody, JA Brookes, K Brown, K Brundin, R Bruni, AC Bullido, MJ Burgess, JD Burke, JR Burns, JM Buxbaum, JD Caffarra, P Cairns, NJ Caltagirone, C Campion, D Cantwell, LB Cao, CH Carlson, CS Carlsson, CM Carney, RM Carrasquillo, MM Carrell, D Carroll, SL Cecchetti, R Chakrabarty, P Chapman, J Chen, Y Choi, SH Chouraki, V Chui, HC Ciaramella, A Clarimon, J Clark, DG Collinge, J Combarros, O Concari, L Corcoran, C Coto, E Craig, D Crane, PK Cribbs, DH Crocco, EA Cruchaga, C Cupidi, C Cupples, LA Daniele, A Daniilidou, M Dartigues, JF De Deyn, PP De Jager, PL DeCarli, C DeStefano, AL Deleuze, JF Denning, N Derbois, C Dermecourt, V Diaz, CC Dichgans, M Dick, M Dickson, DW Dombroski, B Doody, RS Duara, R Dubois, B Dufouil, C Dulary, C Dunstan, M Dupuis, J Eiriksdottir, G Emilsson, V Engelborghs, S Epelbaum, J Ertekin-Taner, N Escott-Price, V Evans, DA Faber, KM Fairchild, TJ Fairen, MD Fallon, KB Fardo, DW Farlow, MR Farrer, LA Fenoglio, C Fernadez, CM Ferris, S Fievet, N Fitzpatrick, AL Fornage, M Foroud, TM Forsell, C Forstner, AJ Forte, J Fox, NC Frank-Garcia, A Fratiglioni, L Frosch, MP Funk, CC Galasko, DR Galimberti, D Gallo, M Garcia, FS Garcia, ME Garzia, F Gearing, M Gerrish, A Geschwind, DH Ghetti, B Giedraitis, V Giegling, I Gilbert, JR Gill, M Goate, AM Golamaully, F Golde, TE Graff, C Graff-Radford, NR Graham, RR Green, RC Grenier-Boley, B Grove, ML Growdon, JH Gu, W Gudnason, V Guerreiro, R Haapasalo, A Haines, JL Hakonarson, H Hamilton, RL Hamilton-Nelson, KL Hampel, H Hannequin, D Hanon, O Hardy, J Harold, D Harrell, LE Hartmann, AM Heilmann-Heimbach, S Helisalmi, S Henandez, I Herms, S Heun, R Hill, M Hiltunen, M Himali, JJ Hodges, A Hoffmann, P Hofman, A Holmans, PA Holmes, C Honig, LS Huebinger, RM Huentelman, MJ Hughes, JT Hulette, CM Hyman, BT Ikram, MA Ingelsson, M Jakobsdottir, J Jarvik, GP Jessen, F Jian, XQ Jin, LW Johnston, J Jones, L Jun, G Kamboh, MI Karydas, A Katz, MJ Kauwe, JK Kaye, JA Keene, CD Keller, L Kilander, L Kim, R Kinhult-Stahlbom, A Kloszewska, I Koivisto, AM Kornhuber, J Kowall, NW Kramer, JH Kukull, WA Kunkle, BW Kuzma, AB LaFerla, FM Lah, JJ Lambert, JC Lannfelt, L Larson, EB Launer, LJ Lawlor, B Leber, M Leverenz, JB Levey, AI Levy, D Li, G Li, HD Li, S Lieberman, AP Lilius, L Lin, HH Lipton, RB Lleo, A Longstreth, WT Lopez, OL Lord, J Lovestone, S Lunetta, KL Lupton, MK Lyketsos, CG Lynch, A Maier, W Majounie, E Malamon, J Maletta, RG Mancuso, M Mann, D Marshall, R Marson, DC Martin, ER Martiniuk, F Mash, DC Masliah, E Masullo, C Mayeux-, R Mayhaus, M McCormick, WC McCurry, SM McDavid, AN McGuinness, B Mckee, AC Mead, S Mecocci, P Medway, C Meggy, A Mesulam, M Miller, BL Miller, CA Miller, JW Moebus, S Montine, TJ Moreno-Grau, S Morgan, K Morgan, T Morris, J Morris, JC Mosley, TH Mukherjee, S Munger, R Murrell, JR Myers, AJ Nacmias, B Naj, AC Naranjo, MCD Norton, M Nothen, MM O'Bryant, S O'Donnell, CJ O'Donovan, MC Olaso, R Orfei, MD Ortega-Cubero, S Owen, MJ Pankratz, VS Panza, F Parisi, JE Pasquier, F Passmore, P Pastor, P Patel, Y Paulson, HL Pericak-Vance, MA Perry, W Peskind, E Peters, O Petersen, RC Pichler, S Pierce, A Pilotto, A Poon, WW Potter, H Powell, J Price, ND Proitsi, P Psaty, BM Qu, LM Quinn, JF Raj, A Ramirez, A Raskind, M Raybould, R Reiman, EM Reisberg, B Reisch, JS Reitz, C Riedel-Heller, S Riemenschneider, M Ringman, JM Ritchie, K Rivadeneira, F Roberson, ED Rogaeva, E Rosen, HJ Rosenberg, RN Rotter, JI Royall, DR Rubinsztein, DC Ruiz, A Rujescu, D Sacchinelli, E Sager, MA Sanchez-Juan, P Sano, M Satizabal, CL Saykin, AJ Scarpini, E Schellenberg, GD Scherer, M Schmidt, H Schmidt, R Schneider, JA Schneider, LS Seeley, WW Septier, G Seripa, D Serpente, M Seshadri, S Shaw, CE Sims, R Sleegers, K Smith, AG Smith, AV Soininen, H Solfrizzi, V Sonnen, JA Sorbi, S Sotolongo-Grau, O Spalletta, G Spina, S Squassina, A St George-Hyslop, P Stern, RA Sussams, R Swerdlow, RH Tanzi, RE Tarraga, L Taylor, S Thomas, C Thomas, R Thonberg, H Thornton-Wells, TA Todd, S Trojanowski, JQ Troncoso, JC Tschanz, J Tsolaki, M Tsuang, DW Turton, J Tzourio, C Uitterlinden, AG Uphill, J Urbano, M Valladares, O Van Broeckhoven, C Van Deerlin, VM Van Eldik, LJ Vandenberghe, R Vardarajan, BN Vellas, B Vinters, HV Vonsattel, JP Vronskaya, M Wallon, D Wang, LS Wang, X Weintraub, S Welsh-Bohmer, KA White, CC Whitehead, P Wilhelmsen, KC Williams, J Williamson, J Winslow, AR Wolters, FJ Woltjer, RL Wright, CB Wu, CK Yang, Q Younkin, SG Yu, CE Yu, L Zhao, Y van Duijn, CM van der Lee, SJ |
| author_facet | Sims, 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 Nothen, MM White, CC Hamilton-Nelson, KL Epelbaum, J Maier, W Choi, SH Beecham, GW Dulary, C Herms, S Smith, AV Funk, CC Derbois, C Forstner, AJ Ahmad, S Li, HD Bacq, D Harold, D Satizabal, CL Valladares, O Squassina, A Thomas, R Brody, JA Qu, LM Sanchez-Juan, P Morgan, T Wolters, FJ Zhao, Y Garcia, FS Denning, N Fornage, M Malamon, J Naranjo, MCD Majounie, E Mosley, TH Dombroski, B Wallon, D Lupton, MK Dupuis, J Whitehead, P Fratiglioni, L Medway, C Jian, XQ Mukherjee, S Keller, L Brown, K Lin, HH Cantwell, LB Panza, F McGuinness, B Moreno-Grau, S Burgess, JD Solfrizzi, V Proitsi, P Adams, HH Allen, M Seripa, D Pastor, P Cupples, LA Price, ND Hannequin, D Frank-Garcia, 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 Henandez, 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 Longstreth, WT Fairchild, TJ Bossu, P Lopez, OL Frosch, MP Sacchinelli, E Ghetti, B Yang, Q Huebinger, RM Jessen, F Li, S Kamboh, MI 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 Fairen, MD 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, MD Ciaramella, A Pichler, S Mayhaus, M Gu, W Lleo, A Forte, J Blesa, R Barber, IS Brookes, K Cupidi, C Maletta, RG 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, CH Carlson, CS Carlsson, CM Carney, RM Carrasquillo, MM Carroll, SL Diaz, CC 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, LW 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 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, JP Weintraub, S Welsh-Bohmer, KA Wilhelmsen, KC Williamson, J Woltjer, RL Wright, CB Yu, CE Yu, L Garzia, F Golamaully, F Septier, G Engelborghs, S Vandenberghe, R De Deyn, PP Fernadez, CM Benito, YA Thonberg, H Forsell, C Lilius, L Kinhult-Stahlbom, A Kilander, L Brundin, R Concari, L Helisalmi, S Koivisto, AM Haapasalo, A Dermecourt, V Fievet, N Hanon, O Dufouil, C Brice, A Ritchie, K Dubois, B Himali, JJ Keene, CD Tschanz, J 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, AC 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, CK 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, JF DeStefano, AL Ortega-Cubero, S Hakonarson, H Campion, D Boada, M Kauwe, JK Farrer, LA Van Broeckhoven, C Ikram, MA Jones, L Haines, JL Tzourio, C Launer, LJ Escott-Price, V Mayeux-, R Deleuze, JF Amin, N Holmans, PA Pericak-Vance, MA Amouyel, P van Duijn, CM Ramirez, A Wang, LS Lambert, JC Seshadri, S Williams, J Schellenberg, GD |
| author_role | author |
| collection | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| description | 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 < 1 x 10(-4)) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 x 10(-8)) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p. Pro522Arg, P = 5.38 x 10(-10), odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p. Ser209Phe, P = 4.56 x 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p. Arg62His, P = 1.55 x 10(-14), OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_c6ece716caed327c4b5736bcafe495ff |
| institution | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| instname_str | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:iibsantpau.fundanetsuite.com:p14146 |
| publishDate | 2017 |
| publishDateSort | 2017 |
| publisher | NATURE PUBLISHING GROUP |
| publisherStr | NATURE PUBLISHING GROUP |
| reponame_str | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| spelling | Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease Sims, 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 Nothen, MM White, CC Hamilton-Nelson, KL Epelbaum, J Maier, W Choi, SH Beecham, GW Dulary, C Herms, S Smith, AV Funk, CC Derbois, C Forstner, AJ Ahmad, S Li, HD Bacq, D Harold, D Satizabal, CL Valladares, O Squassina, A Thomas, R Brody, JA Qu, LM Sanchez-Juan, P Morgan, T Wolters, FJ Zhao, Y Garcia, FS Denning, N Fornage, M Malamon, J Naranjo, MCD Majounie, E Mosley, TH Dombroski, B Wallon, D Lupton, MK Dupuis, J Whitehead, P Fratiglioni, L Medway, C Jian, XQ Mukherjee, S Keller, L Brown, K Lin, HH Cantwell, LB Panza, F McGuinness, B Moreno-Grau, S Burgess, JD Solfrizzi, V Proitsi, P Adams, HH Allen, M Seripa, D Pastor, P Cupples, LA Price, ND Hannequin, D Frank-Garcia, 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 Henandez, 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 Longstreth, WT Fairchild, TJ Bossu, P Lopez, OL Frosch, MP Sacchinelli, E Ghetti, B Yang, Q Huebinger, RM Jessen, F Li, S Kamboh, MI 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 Fairen, MD 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, MD Ciaramella, A Pichler, S Mayhaus, M Gu, W Lleo, A Forte, J Blesa, R Barber, IS Brookes, K Cupidi, C Maletta, RG 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, CH Carlson, CS Carlsson, CM Carney, RM Carrasquillo, MM Carroll, SL Diaz, CC 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, LW 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 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, JP Weintraub, S Welsh-Bohmer, KA Wilhelmsen, KC Williamson, J Woltjer, RL Wright, CB Yu, CE Yu, L Garzia, F Golamaully, F Septier, G Engelborghs, S Vandenberghe, R De Deyn, PP Fernadez, CM Benito, YA Thonberg, H Forsell, C Lilius, L Kinhult-Stahlbom, A Kilander, L Brundin, R Concari, L Helisalmi, S Koivisto, AM Haapasalo, A Dermecourt, V Fievet, N Hanon, O Dufouil, C Brice, A Ritchie, K Dubois, B Himali, JJ Keene, CD Tschanz, J 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, AC 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, CK 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, JF DeStefano, AL Ortega-Cubero, S Hakonarson, H Campion, D Boada, M Kauwe, JK Farrer, LA Van Broeckhoven, C Ikram, MA Jones, L Haines, JL Tzourio, C Launer, LJ Escott-Price, V Mayeux-, R Deleuze, JF Amin, N Holmans, PA Pericak-Vance, MA Amouyel, P van Duijn, CM Ramirez, A Wang, LS Lambert, JC Seshadri, S Williams, J Schellenberg, GD 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 < 1 x 10(-4)) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 x 10(-8)) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p. Pro522Arg, P = 5.38 x 10(-10), odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p. Ser209Phe, P = 4.56 x 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p. Arg62His, P = 1.55 x 10(-14), OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease. NATURE PUBLISHING GROUP https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14146 https://europepmc.org/articles/pmc5669039 |
| spellingShingle | Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease Sims, R |
| status_str | publishedVersion |
| title | Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease |
| title_full | Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease |
| title_fullStr | Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease |
| title_full_unstemmed | Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease |
| title_short | Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease |
| title_sort | Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease |
| url | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14146 https://europepmc.org/articles/pmc5669039 |