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

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

doi:10.1016/j.dadm.2018.08.008

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

Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease / G.M. Peloso, S.J. van der Lee, R. Sims, S.J. van der Lee, A.C. Naj, C. Bellenguez, N. Badarinarayan, J. Jakobsdottir, B.W. Kunkle, A. Boland, R. Raybould, J.C. Bis, E.R. Martin, B. Grenier-Boley, S. Heilmann-Heimbach, V. Chouraki, A.B. Kuzma, K. Sleegers, M. Vronskaya, A. Ruiz, R.R. Graham, R. Olaso, P. Hoffmann, M.L. Grove, B.N. Vardarajan, M. Hiltunen, M.M. Nöthen, C.C. White, K.L. Hamilton-Nelson, J. Epelbaum, W. Maier, S.H. Choi, G.W. Beecham, C. Dulary, S. Herms, A.V. Smith, C.C. Funk, N. Derbois, A.J. Forstner, S. Ahmad, H. Li, D. Bacq, D. Harold, C.L. Satizabal, O. Valladares, A. Squassina, R. Thomas, J.A. Brody, L. Qu, P. Sánchez-Juan, T. Morgan, F.J. Wolters, Y. Zhao, F.S. Garcia, N. Denning, M. Fornage, J. Malamon, M.C.D. Naranjo, E. Majounie, T.H. Mosley, B. Dombroski, D. Wallon, M.K. Lupton, J. Dupuis, P. Whitehead, L. Fratiglioni, C. Medway, X. Jian, S. Mukherjee, L. Keller, K. Brown, H. Lin, L.B. Cantwell, F. Panza, B. Mcguinness, S. Moreno-Grau, J.D. Burgess, V. Solfrizzi, P. Proitsi, H.H. Adams, M. Allen, D. Seripa, P. Pastor, L.A. Cupples, N.D. Price, D. Hannequin, A. Frank-García, D. Levy, P. Chakrabarty, P. Caffarra, I. Giegling, A.S. Beiser, V. Giedraitis, H. Hampel, M.E. Garcia, X. Wang, L. Lannfelt, P. Mecocci, G. Eiriksdottir, P.K. Crane, F. Pasquier, V. Boccardi, I. Henández, R.C. Barber, M. Scherer, L. Tarraga, P.M. Adams, M. Leber, Y. Chen, M.S. Albert, S. Riedel-Heller, V. Emilsson, D. Beekly, A. Braae, R. Schmidt, D. Blacker, C. Masullo, H. Schmidt, R.S. Doody, G. Spalletta, W.T. Longstreth, T.J. Fairchild, P. Bossù, O.L. Lopez, M.P. Frosch, E. Sacchinelli, B. Ghetti, Q. Yang, R.M. Huebinger, F. Jessen, S. Li, M.I. Kamboh, J. Morris, O. Sotolongo-Grau, M.J. Katz, C. Corcoran, M. Dunstan, A. Braddel, C. Thomas, A. Meggy, R. Marshall, A. Gerrish, J. Chapman, M. Aguilar, S. Taylor, M. Hill, M.D. Fairén, A. Hodges, B. Vellas, H. Soininen, I. Kloszewska, M. Daniilidou, J. Uphill, Y. Patel, J.T. Hughes, J. Lord, J. Turton, A.M. Hartmann, R. Cecchetti, C. Fenoglio, M. Serpente, M. Arcaro, C. Caltagirone, M.D. Orfei, A. Ciaramella, S. Pichler, M. Mayhaus, W. Gu, A. Lleó, J. Fortea, R. Blesa, I.S. Barber, K. Brookes, C. Cupidi, R.G. Maletta, D. Carrell, S. Sorbi, S. Moebus, M. Urbano, A. Pilotto, J. Kornhuber, P. Bosco, S. Todd, D. Craig, J. Johnston, M. Gill, B. Lawlor, A. Lynch, N.C. Fox, J. Hardy, R.L. Albin, L.G. Apostolova, S.E. Arnold, S. Asthana, C.S. Atwood, C.T. Baldwin, L.L. Barnes, S. Barral, T.G. Beach, J.T. Becker, E.H. Bigio, T.D. Bird, B.F. Boeve, J.D. Bowen, A. Boxer, J.R. Burke, J.M. Burns, J.D. Buxbaum, N.J. Cairns, C. Cao, C.S. Carlson, C.M. Carlsson, R.M. Carney, M.M. Carrasquillo, S.L. Carroll, C.C. Diaz, H.C. Chui, D.G. Clark, D.H. Cribbs, E.A. Crocco, C. Decarli, M. Dick, R. Duara, D.A. Evans, K.M. Faber, K.B. Fallon, D.W. Fardo, M.R. Farlow, S. Ferris, T.M. Foroud, D.R. Galasko, M. Gearing, D.H. Geschwind, J.R. Gilbert, N.R. Graff-Radford, R.C. Green, J.H. Growdon, R.L. Hamilton, L.E. Harrell, L.S. Honig, M.J. Huentelman, C.M. Hulette, B.T. Hyman, G.P. Jarvik, E. Abner, L.W. Jin, G. Jun, A. Karydas, J.A. Kaye, R. Kim, N.W. Kowall, J.H. Kramer, F.M. Laferla, J.J. Lah, J.B. Leverenz, A.I. Levey, G. Li, A.P. Lieberman, K.L. Lunetta, C.G. Lyketsos, D.C. Marson, F. Martiniuk, D.C. Mash, E. Masliah, W.C. Mccormick, S.M. Mccurry, A.N. Mcdavid, A.C. Mckee, M. Mesulam, B.L. Miller, C.A. Miller, J.W. Miller, J.C. Morris, J.R. Murrell, A.J. Myers, S. O'Bryant, J.M. Olichney, V.S. Pankratz, J.E. Parisi, H.L. Paulson, W. Perry, E. Peskind, A. Pierce, W.W. Poon, H. Potter, J.F. Quinn, A. Raj, M. Raskind, B. Reisberg, C. Reitz, J.M. Ringman, E.D. Roberson, E. Rogaeva, H.J. Rosen, R.N. Rosenberg, M.A. Sager, A.J. Saykin, J.A. Schneider, L.S. Schneider, W.W. Seeley, A.G. Smith, J.A. Sonnen, S. Spina, R.A. Stern, R.H. Swerdlow, R.E. Tanzi, T.A. Thornton-Wells, J.Q. Trojanowski, J.C. Troncoso, V.M. Van Deerlin, L.J. Van Eldik, H.V. Vinters, J.P. Vonsattel, S. Weintraub, K.A. Welsh-Bohmer, K.C. Wilhelmsen, J. Williamson, T.S. Wingo, R.L. Woltjer, C.B. Wright, C.E. Yu, L. Yu, F. Garzia, F. Golamaully, G. Septier, S. Engelborghs, R. Vandenberghe, P.P. De Deyn, C.M. Fernadez, Y.A. Benito, H. Thonberg, C. Forsell, L. Lilius, A. Kinhult-Stählbom, L. Kilander, R. Brundin, L. Concari, S. Helisalmi, A.M. Koivisto, A. Haapasalo, V. Dermecourt, N. Fievet, O. Hanon, C. Dufouil, A. Brice, K. Ritchie, B. Dubois, J.J. Himali, C.D. Keene, J. Tschanz, A.L. Fitzpatrick, W.A. Kukull, M. Norton, T. Aspelund, E.B. Larson, R. Munger, J.I. Rotter, R.B. Lipton, M.J. Bullido, A. Hofman, T.J. Montine, E. Coto, E. Boerwinkle, R.C. Petersen, V. Alvarez, F. Rivadeneira, E.M. Reiman, M. Gallo, C.J. O'Donnell, J.S. Reisch, A.C. Bruni, D.R. Royall, M. Dichgans, M. Sano, D. Galimberti, P. St George-Hyslop, E. Scarpini, D.W. Tsuang, M. Mancuso, U. Bonuccelli, A.R. Winslow, A. Daniele, C.K. Wu, O. Peters, B. Nacmias, M. Riemenschneider, R. Heun, C. Brayne, D.C. Rubinsztein, J. Bras, R. Guerreiro, A. Al-Chalabi, C.E. Shaw, J. Collinge, D. Mann, M. Tsolaki, J. Clarimón, R. Sussams, S. Lovestone, M.C. O'Donovan, M.J. Owen, T.W. Behrens, S. Mead, A.M. Goate, A.G. Uitterlinden, C. Holmes, C. Cruchaga, M. Ingelsson, D.A. Bennett, J. Powell, T.E. Golde, C. Graff, P.L. De Jager, K. Morgan, N. Ertekin-Taner, O. Combarros, B.M. Psaty, P. Passmore, S.G. Younkin, C. Berr, V. Gudnason, D. Rujescu, D.W. Dickson, J.F. Dartigues, A.L. Destefano, S. Ortega-Cubero, H. Hakonarson, D. Campion, M. Boada, J.K. Kauwe, L.A. Farrer, C. Van Broeckhoven, M.A. Ikram, L. Jones, J.L. Haines, C. Tzourio, L.J. Launer, V. Escott-Price, R. Mayeux, J.F. Deleuze, N. Amin, P.A. Holmans, M.A. Pericak-Vance, P. Amouyel, C.M. van Duijn, A. Ramirez, L.S. Wang, J.C. Lambert, S. Seshadri, J. Williams, G.D. Schellenberg, A.L. Destefano, S. Seshardi. - In: ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING. - ISSN 2352-8729. - 10:(2018 Jan 01), pp. 595-598. [10.1016/j.dadm.2018.08.008]

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

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

2018

Abstract

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

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	Parole chiave
	
			Cholesteryl ester transfer protein; Genetics; HDL-C; Instrumental variables; Single nucleotide polymorphisms; Neurology (clinical); Psychiatry and Mental Health
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore BIO/13 - Biologia Applicata
Settore MED/26 - Neurologia
		
	Data di pubblicazione
	
			1-gen-2018
		
	Rivista in ANCE
	
			ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
		
	DOI
	
			https://dx.doi.org/10.1016/j.dadm.2018.08.008
		
	Tipologia
	
			Article (author)
		
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			01 - Articolo su periodico

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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/635452

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