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

Peloso, GM, van der Lee, SJ, Destefano, AL, Seshardi, S, 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, Nöthen, MM, White, CC, Hamilton-Nelson, KL, Epelbaum, J, Maier, W, Choi, SH, Beecham, GW, Dulary, C, Herms, S, Smith, AV, Funk, CC, Derbois, Forstner, A, 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, 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, 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, Cupples, LA, 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, Longstreth, WT, Fairchild, TJ, Bossù, 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, Fairén, 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, Lleó, A, Fortea, J, Blesa, R, Barber, IS, Brookes, K ORCID: https://orcid.org/0000-0003-2427-2513, 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, C, 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, 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, JP, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, 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-Stählbom, 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, Clarimón, 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 and Schellenberg, GD, 2018. Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 10, pp. 595-598. ISSN 2352-8729

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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.

Item Type:	Journal article
Publication Title:	Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Creators:	Peloso, G.M., van der Lee, S.J., Destefano, A.L., Seshardi, S., Sims, R., Van der Lee, S.J., Naj, A.C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B.W., Boland, A., Raybould, R., Bis, J.C., Martin, E.R., Grenier-Boley, B., Heilmann-Heimbach, S., Chouraki, V., Kuzma, A.B., Sleegers, K., Vronskaya, M., Ruiz, A., Graham, R.R., Olaso, R., Hoffmann, P., Grove, M.L., Vardarajan, B.N., Hiltunen, M., Nöthen, M.M., White, C.C., Hamilton-Nelson, K.L., Epelbaum, J., Maier, W., Choi, S.H., Beecham, G.W., Dulary, C., Herms, S., Smith, A.V., Funk, C.C., Derbois, Forstner, A., 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., Yu, C.E., Yu, L., Garzia, F., Golamaully, F., Septier, G., Engelborghs, S., Vandenberghe, R., De Deyn, P.P., Fernadez, C.M., Benito, Y.A., Thonberg, H., Forsell, C., Lilius, L., Kinhult-Stählbom, A., Kilander, L., Brundin, R., Concari, L., Helisalmi, S., Koivisto, A.M., Haapasalo, A., Dermecourt, V., Fievet, N., Hanon, O., Dufouil, C., Brice, A., Ritchie, K., Dubois, B., Himali, J.J., Keene, C.D., Tschanz, J., Fitzpatrick, A.L., Kukull, W.A., Norton, M., Aspelund, T., Larson, E.B., Munger, R., Rotter, J.I., Lipton, R.B., Bullido, M.J., Hofman, A., Montine, T.J., Coto, E., Boerwinkle, E., Petersen, R.C., Alvarez, V., Rivadeneira, F., Reiman, E.M., Gallo, M., O'Donnell, C.J., Reisch, J.S., Bruni, A.C., Royall, D.R., Dichgans, M., Sano, M., Galimberti, D., St George-Hyslop, P., Scarpini, E., Tsuang, D.W., Mancuso, M., Bonuccelli, U., Winslow, A.R., Daniele, A., Wu, C.K., Peters, O., Nacmias, B., Riemenschneider, M., Heun, R., Brayne, C., Rubinsztein, D.C., Bras, J., Guerreiro, R., Al-Chalabi, A., Shaw, C.E., Collinge, J., Mann, D., Tsolaki, M., Clarimón, J., Sussams, R., Lovestone, S., O'Donovan, M.C., Owen, M.J., Behrens, T.W., Mead, S., Goate, A.M., Uitterlinden, A.G., Holmes, C., Cruchaga, C., Ingelsson, M., Bennett, D.A., Powell, J., Golde, T.E., Graff, C., De Jager, P.L., Morgan, K., Ertekin-Taner, N., Combarros, O., Psaty, B.M., Passmore, P., Younkin, S.G., Berr, C., Gudnason, V., Rujescu, D., Dickson, D.W., Dartigues, J.F., DeStefano, A.L., Ortega-Cubero, S., Hakonarson, H., Campion, D., Boada, M., Kauwe, J.K., Farrer, L.A., Van Broeckhoven, C., Ikram, M.A., Jones, L., Haines, J.L., Tzourio, C., Launer, L.J., Escott-Price, V., Mayeux, R., Deleuze, J.F., Amin, N., Holmans, P.A., Pericak-Vance, M.A., Amouyel, P., Van Duijn, C.M., Ramirez, A., Wang, L.S., Lambert, J.C., Seshadri, S., Williams, J. and Schellenberg, G.D.
Publisher:	Elsevier
Date:	22 September 2018
Volume:	10
ISSN:	2352-8729
Identifiers:	Number Type 10.1016/j.dadm.2018.08.008 DOI S2352872918300605 Publisher Item Identifier
Rights:	© 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer’s Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	13 May 2019 11:02
Last Modified:	11 Sep 2019 14:36
URI:	https://irep.ntu.ac.uk/id/eprint/36460

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