1. A novel Alzheimer disease locus located near the gene encoding tau protein
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Jun, G., Ibrahim-Verbaas, C.A., Vronskaya, M., Lambert, J.-., Chung, J., Naj, A.C., Kunkle, B.W., Wang, L.-., Bis, J.C., Bellenguez, C., Harold, D., Lunetta, K.L., Destefano, A.L., Grenier-Boley, B., Sims, R., Beecham, G.W., Smith, A.V., Chouraki, V., Hamilton-Nelson, K.L., Ikram, M.A., Fievet, N., Denning, N., Martin, E.R., Schmidt, H., Kamatani, Y., Dunstan, M.L., Valladares, O., Laza, A.R., Zelenika, D., Ramirez, A., Foroud, T.M., Choi, S.-., Boland, A., Becker, T., Kukull, W.A., Van Der Lee, S.J., Pasquier, F., Cruchaga, C., Beekly, D., Fitzpatrick, A.L., Hanon, O., Gill, M., Barber, R., Gudnason, V., Campion, D., Love, S., Bennett, D.A., Amin, N., Berr, C., Tsolaki, M., Buxbaum, J.D., Lopez, O.L., Deramecourt, V., Fox, N.C., Cantwell, L.B., Tárraga, L., Dufouil, C., Hardy, J., Crane, P.K., Eiriksdottir, G., Hannequin, D., Clarke, R., Evans, D., Mosley, T.H., Letenneur, L., Brayne, C., Maier, W., De Jager, P., Emilsson, V., Dartigues, J.-., Hampel, H., Kamboh, M.I., De Bruijn, R.F.A.G., Tzourio, C., Pastor, P., Larson, E.B., Rotter, J.I., O'Donovan, M.C., Montine, T.J., Nalls, M.A., Mead, S., Reiman, E.M., Jonsson, P.V., Holmes, C., St George-Hyslop, P.H., Boada, M., Passmore, P., Wendland, J.R., Schmidt, R., Morgan, K., Winslow, A.R., Powell, J.F., Carasquillo, M., Younkin, S.G., Jakobsdóttir, J., Kauwe, J.S.K., Wilhelmsen, K.C., Rujescu, D., Nöthen, M.M., Hofman, A., Jones, L., Haines, J.L., Psaty, B.M., Van Broeckhoven, C., Holmans, P., Launer, L.J., Mayeux, R., Lathrop, M., Goate, A.M., Escott-Price, V., Seshadri, S., Pericak-Vance, M.A., Amouyel, P., Williams, J., Van Duijn, C.M., Schellenberg, G.D., Farrer, L.A., Adams, P.M., Albert, M.S., Albin, R.L., Apostolova, L.G., Arnold, S.E., Asthana, S., Atwood, C.S., Baldwin, C.T., Barmada, M.M., Barnes, L.L., Beach, T.G., Becker, J.T., Bigio, E.H., Bird, T.D., Blacker, D., Boeve, B.F., Bowen, J.D., Boxer, A., Burke, J.R., Cairns, N.J., Cao, C., Carlson, C.S., Carlsson, C.M., Carney, R.M., Carrasquillo, M.M., Carroll, S.L., Chui, H.C., Clark, D.G., Corneveaux, J., Cribbs, D.H., Crocco, E.A., De Jager, P.L., Decarli, C., Dekosky, S.T., Yesim Demirci, F., Dick, M., Dickson, D.W., Doody, R.S., Duara, R., Ertekin-Taner, N., Faber, K.M., Fairchild, T.J., Fallon, K.B., Farlow, M.R., Ferris, S., Frosch, M.P., Galasko, D.R., Gearing, M., Geschwind, D.H., Ghetti, B., Gilbert, J.R., Glass, J.D., Graff-Radford, N.R., Green, R.C., Growdon, J.H., Hakonarson, H., Hamilton, R.L., Harrell, L.E., Head, E., Honig, L.S., Huebinger, R.M., Huentelman, M.J., Hulette, C.M., Hyman, B.T., Jarvik, G.P., Jicha, G.A., Jin, L., Karydas, A., Kaye, J.A., Kim, R., Koo, E.H., Kowall, N.W., Kramer, J.H., Laferla, F.M., Lah, J.J., Leverenz, J.B., Levey, A.I., Ge, L., Lieberman, A.P., Lin, C., Lyketsos, C.G., Mack, W.J., 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., Mukherjee, S., Murrell, J.R., Myers, A.J., O'Bryant, S., Olichney, J.M., Pankratz, V.S., Parisi, J.E., Partch, A., Paulson, H.L., Perry, W., Peskind, E., Petersen, R.C., Pierce, A., Poon, W.W., Potter, H., Quinn, J.F., Raj, A., Raskind, M., Reisberg, B., Reisch, J.S., Reitz, C., Ringman, J.M., Roberson, E.D., Rogaeva, E., Rosen, H.J., Rosenberg, R.N., Royall, D.R., Sager, M.A., Sano, M., Saykin, A.J., Schneider, J.A., Schneider, L.S., Seeley, W.W., Smith, A.G., Sonnen, J.A., Spina, S., Stern, R.A., Tanzi, R.E., Thornton-Wells, T.A., Trojanowski, J.Q., Troncoso, J.C., Tsuang, D.W., Van Deerlin, V.M., Van Eldik, L.J., Vardarajan, B.N., Vinters, H.V., Vonsattel, J.P., Weintraub, S., Welsh-Bohmer, K.A., Williamson, J., Wishnek, S., Woltjer, R.L., Wright, C.B., Chuang-Kuo, W., Chang-En, Y., Lei, Y., Thomas, C., Gerrish, A., Chapman, J., Stretton, A., Morgan, A., Oldham, H., Owen, M.J., Kehoe, P.G., Medway, C., Brown, K., Lord, J., Turton, J., Hooper, N.M., Vardy, E., Warren, J.D., Schott, J.M., Uphill, J., Hollingworth, P., Ryan, N., Rossor, M., Collinge, J., Ben-Shlomo, Y., Makrina, D., Gkatzima, O., Lupton, M., Koutroumani, M., Avramidou, D., Germanou, A., Jessen, F., Riedel-Heller, S., Dichgans, M., Heun, R., Kölsch, H., Schürmann, B., Herold, C., Lacour, A., Drichel, D., Hoffmann, P., Kornhuber, J., Wei, G., Feulner, T., Mayhaus, M., Pichler, S., Riemenschneider, M., van den Bussche, H., Lawlor, B., Lynch, A., Mann, D., Smith, A.D., Warden, D., Wilcock, G., Heuser, I., Wiltfang, J., Frölich, L., Hüll, M., Mayo, K., Livingston, G., Bass, N.J., Gurling, H., Mcquillin, A., Gwilliam, R., Deloukas, P., Al-Chalabi, A., Shaw, C.E., Singleton, A.B., Guerreiro, R., Russo, G., Jöckel, K., Moebus, S., Klopp, N., Wichmann, H.-., Li, M., Bisceglio, G., Fisher, E., Warner, N., Pickering-Brown, S., Craig, D., Johnston, J.A., Mcguinness, B., Todd, S., Rubinsztein, D.C., Lovestone, S., Bayer, A., Gallacher, J., Proitsi, P., Ortega-Cubero, Saraadams, P., Albert, M., Albin, R., Apostolova, L., Arnold, S., Atwood, C., Baldwin, C., Barmada, M., Barnes, L., Beach, T., Becker, J., Bigio, E., Bird, T., Boeve, B., Bowen, J., Burke, J., Cairns, N., Carlson, C., Carlsson, C., Carney, R., Carrasquillo, M., Carroll, S., Chui, H., Clark, D., Cribbs, D., Crocco, E., De Jager PL, Dekosky, S., Demirci, F., Dickson, D., Doody, R., Faber, K., Fairchild, T., Fallon, K., Farlow, M., Frosch, M., Galasko, D., Geschwind, D., Gilbert, J., Glass, J., Graff-Radford, N., Green, R., Growdon, J., Hamilton, R., Harrell, L., Honig, L., Huebinger, R., Huentelman, M., Hulette, C., Hyman, B., Jarvik, G., Jicha, G., Kauwe, J., Kaye, J., Koo, E., Kowall, N., Kramer, J., Laferla, F., Lah, J., Leverenz, J., Levey, A., Li, G., Lieberman, A., Lopez, O., Lyketsos, C., Mack, W., Marson, D., Mash, D., Mccormick, W., Mccurry, S., Mcdavid, A., Mckee, A., Miller, B., Miller, C., Miller, J., Morris, J., Murrell, J., Myers, A., Olichney, J., Pankratz, V., Parisi, J., Paulson, H., Petersen, R., Poon, W., Quinn, J., Reisch, J., Ringman, J., Roberson, E., Rosen, H., Rosenberg, R., Royall, D., Sager, M., Saykin, A., Schneider, J., Schneider, L., Seeley, W., Smith, A., Sonnen, J., Stern, R., Tanzi, R., Thornton-Wells, T., Trojanowski, J., Troncoso, J., Tsuang, D., Van Deerlin VM, Van Eldik LJ, Vardarajan, B., Vinters, H., Vonsattel, J., Welsh-Bohmer, K., Woltjer, R., Wright, C., Wu, C., Yu, C., Yu, L., Au, R., Wolf, P., Beiser, A., Satizabal, C., Uitterlinden, A., Rivadeneira, F., Koudstaal, P., Longstreth WT Jr, Kuller, L., Lumley, T., Rice, K., Harris, T., Nalls, M., Marksteiner, J., Dal-Bianco, P., Töglhofer, A., Freudenberger, P., Ransmayr, G., Benke, T., Toeglhofer, A., Boerwinkle, E., Bressler, J., Fornage, M., Morón, F., Hernández, I., Roca, M., Mauleón, A., Alegret, M., Ramírez-Lorca, R., González-Perez, A., Alpérovitch, A., Alvarez, V., Barberger-Gateau, P., Bettens, K., Bossù, P., Brice, A., Bullido, M., Caffara, P., Clarimon, J., Combarros, O., Coto, E., Del Zampo, M., Delepine, M., Deniz Naranjo MC, Epelbaum, J., Fratiglioni, L., Galimberti, D., Graff, C., Hiltunen, M., Ingelsson, M., Keller, L., Lannfelt, L., Llèo, A., Mancuso, M., Mateo, I., Mecocci, P., Nacmias, B., Panza, F., Pilotto, A., Garcia, F., Scarpini, E., Seripa, D., Sleegers, K., Soininen, H., Sorbi, S., Spalletta, G., Wallon, D., Owen, M., Kehoe, P., Hooper, N., Warren, J., Schott, J., Gu, W., Bass, N., Shaw, C., Singleton, A., Wichmann, H., Ma, L., Johnston, J., Rubinsztein, D., Ortega-Cubero, S., Epidemiology, Neurology, and Internal Medicine
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0301 basic medicine ,Apolipoprotein E ,Apolipoprotein E4 ,Single-nucleotide polymorphism ,Locus (genetics) ,Genome-wide association study ,genetics [Alzheimer Disease] ,MAPT protein, human ,tau Proteins ,Polymorphism, Single Nucleotide ,Article ,Chromosomes ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Alzheimer Disease ,Settore BIO/13 - Biologia Applicata ,Humans ,ddc:610 ,Polymorphism ,Molecular Biology ,Biology ,genetics [Apolipoprotein E4] ,Genetic association ,Temporal cortex ,Genetics ,Pair 17 ,Haplotype ,Single Nucleotide ,3. Good health ,Chromosome 17 (human) ,genetics [tau Proteins] ,Chemistry ,030104 developmental biology ,Psychiatry and Mental Health ,Chromosomes, Human, Pair 17 ,Genome-Wide Association Study ,Settore MED/26 - Neurologia ,Human medicine ,Psychology ,030217 neurology & neurosurgery ,Human - Abstract
APOE epsilon 4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE epsilon 4+ (10 352 cases and 9207 controls) and APOE epsilon 4 - (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE e4 status. Suggestive associations (P < 1x10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE epsilon 4+: 1250 cases and 536 controls; APOE epsilon 4 -: 718 cases and 1699 controls). Among APOE epsilon 4 - subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P = 5.8 x 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE epsilon 4+ subjects (CR1 and CLU) or APOE epsilon 4 - subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P = 1.6 x 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P
- Published
- 2016
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