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1. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimerʼs disease

Author

Lambert, J-C, Grenier-Boley, B, Harold, D, Zelenika, D, Chouraki, V, Kamatani, Y, Sleegers, K, Ikram, M A, Hiltunen, M, Reitz, C, Mateo, I, Feulner, T, Bullido, M, Galimberti, D, Concari, L, Alvarez, V, Sims, R, Gerrish, A, Chapman, J, Deniz-Naranjo, C, Solfrizzi, V, Sorbi, S, Arosio, B, Spalletta, G, Siciliano, G, Epelbaum, J, Hannequin, D, Dartigues, J-F, Tzourio, C, Berr, C, Schrijvers, E MC, Rogers, R, Tosto, G, Pasquier, F, Bettens, K, Van Cauwenberghe, C, Fratiglioni, L, Graff, C, Delepine, M, Ferri, R, Reynolds, C A, Lannfelt, L, Ingelsson, M, Prince, J A, Chillotti, C, Pilotto, A, Seripa, D, Boland, A, Mancuso, M, Bossù, P, Annoni, G, Nacmias, B, Bosco, P, Panza, F, Sanchez-Garcia, F, Del Zompo, M, Coto, E, Owen, M, OʼDonovan, M, Valdivieso, F, Caffara, P, Scarpini, E, Combarros, O, Buée, L, Campion, D, Soininen, H, Breteler, M, Riemenschneider, M, Van Broeckhoven, C, Alpérovitch, A, Lathrop, M, Trégouët, D-A, Williams, J, Amouyel, P, consortium, E ADI, and consortium, G ERAD

Published
2013
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3. Genetic Aspects of Epilepsy-Aphasia Syndromes

Author

Roll, P., Rudolf, G., Pereira, S., Royer, B., Scheffer, I. E., Valenti, M. P., Metz-Lutz, M. N., Delepine, M., Lévy, N., Berkovic, S. F., Hirsch, E., Lathrop, G. M., Cau, P., and Szepetowski, P.

Published
2005

4. Genetic mapping of a susceptibility locus for insulin-dependent diabetes mellitus on chromosome 11q

Author

Hashimoto, L., Habita, C., Beressl, J. P., Delepine, M., Besse, C., Cambon-Thomsen, A., Deschamps, I., Rotter, J.I., Djoulah, S., James, M.R., Froguel, P., Weissenbach, J., Lathrop, G.M., and Julier, C.

Subjects
Type 1 diabetes -- Genetic aspects, Chromosome mapping -- Observations, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A genome-wide linkage study of insulin-dependent diabetes mellitus (IDDM) using microsatellite markers, obtained from genothon maps and other informative markers derived using polymerase chain reaction analysis, localizes an unidentified susceptibility locus for IDDM. The locus is present in the FGF3 gene area on the chromosome 11Q. Genetic linkage studies also facilitate the identification of susceptibility loci in other multifactorial disorders.

Published
1994

5. Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy. (Original Article)

Author

Van Maldergem, L., Magre, J., Khallouf, T.E., Gedde-Dahl, Jr., T., Delepine, M., Trygstad, O., Seemanova, E., Stephenson, T., Albott, C.S., Bonnici, F., Panz, V.R., Medina, J-L, Bogalho, P., Huet, F., Savasta, S., Verloes, A., Robert, J-J, Loret, H., de Kerdanet, M., Tubiana-Rufi, N., Megarbane, A., Maassen, J., Polak, M., Lacombe, D., Kahn, C.R., Silveira, E.L., D'Abronzo, F.H., Grigorescu, F., Lathrop, M., Capeau, J., and O'Rahilly, S.

Subjects
Gene mutations -- Health aspects -- Research -- Genetic aspects, Diabetes -- Genetic aspects -- Research, Medical genetics -- Research -- Health aspects, Lipodystrophy -- Genetic aspects -- Research, Somatotypes -- Genetic aspects -- Health aspects -- Research, Heart failure -- Causes of -- Genetic aspects -- Research, African Americans -- Health aspects -- Research, Health, Research, Genetic aspects, Causes of, Health aspects
Abstract

Generalised lipodystrophy of the Berardinelli-Seip type (BSCL) is a rare autosomal recessive human disorder with severe adverse metabolic consequences. A gene on chromosome 9 (BSCL1) has recently been identified, predominantly [...]

Published
2002

7. Erratum: Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

Author

Lambert, J-C, Grenier-Boley, B, Harold, D, Zelenika, D, Chouraki, V, Kamatani, Y, Sleegers, K, Ikram, M A, Hiltunen, M, Reitz, C, Mateo, I, Feulner, T, Bullido, M, Galimberti, D, Concari, L, Alvarez, V, Sims, R, Gerrish, A, Chapman, J, Deniz-Naranjo, C, Solfrizzi, V, Sorbi, S, Arosio, B, Spalletta, G, Siciliano, G, Epelbaum, J, Hannequin, D, Dartigues, J-F, Tzourio, C, Berr, C, Schrijvers, E M C, Rogers, R, Tosto, G, Pasquier, F, Bettens, K, Van Cauwenberghe, C, Fratiglioni, L, Graff, C, Delepine, M, Ferri, R, Reynolds, C A, Lannfelt, L, Ingelsson, M, Prince, J A, Chillotti, C, Pilotto, A, Seripa, D, Boland, A, Mancuso, M, Bossù, P, Annoni, G, Nacmias, B, Bosco, P, Panza, F, Sanchez-Garcia, F, Zompo, M Del, Coto, E, Owen, M, O'Donovan, M, Valdivieso, F, Caffara, P, Scarpini, E, Combarros, O, Buée, L, Campion, D, Soininen, H, Breteler, M, Riemenschneider, M, Van Broeckhoven, C, Alpérovitch, A, Lathrop, M, Trégouët, D-A, Williams, J, and Amouyel, P

Published
2013
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13. A novel Alzheimer disease locus located near the gene encoding tau protein

Author

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

Subjects
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

14. Lung cancer susceptibility locus at 5p15.33

Author

McKay JD, Hung RJ, Gaborieau V, Boffetta P, Chabrier A, Byrnes G, Zaridze D, Mukeria A, Szeszenia Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, McLaughlin J, Shepherd F, Montpetit A, Narod S, Krokan HE, Skorpen F, Elvestad MB, Vatten L, Njølstad I, Axelsson T, Chen C, Goodman G, Barnett M, Loomis MM, Lubiñski J, Matyjasik J, Lener M, Oszutowska D, Field J, Liloglou T, Xinarianos G, Cassidy A, EPIC Study, Vineis P, Clavel Chapelon F, Palli D, Tumino R, Krogh V, González CA, Ramón Quirós J, Martínez C, Navarro C, Ardanaz E, Larrañaga N, Kham KT, Key T, Bueno de Mesquita HB, Peeters PH, Trichopoulou A, Linseisen J, Boeing H, Hallmans G, Overvad K, Tjønneland A, Kumle M, Riboli E, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Matsuda F, Blanche H, Gut I, Heath S, Lathrop M, Brennan P., PANICO, SALVATORE, McKay, J.D., Hung, R.J., Gaborieau, V., Boffetta, P., Chabrier, A., Byrnes, G., Zaridze, D., Mukeria, A., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Mates, D., Bencko, V., Foretova, L., Janout, V., McLaughlin, J., Shepherd, F., Montpetit, A., Narod, S., Krokan, H.E., Skorpen, F., Elvestad, M.B., Vatten, L., Njølstad, I., Axelsson, T., Chen, C., Goodman, G., Barnett, M., Loomis, M.M., Lubiski, J., Matyjasik, J., Lener, M., Oszutowska, D., Field, J., Liloglou, T., Xinarianos, G., Cassidy, A., Zelenika, D., Boland, A., Delepine, M., Foglio, M., Lechner, D., Matsuda, F., Blanche, H., Gut, I., Heath, S., Lathrop, M., Brennan, P., Vineis, P., Clavel-Chapelon, F., Palli, D., Tumino, R., Krogh, V., Panico, S., González, C.A., Ramón Quirós, J., Martínez, C., Navarro, C., Ardanaz, E., Larrãaga, N., Kham, K.T., Key, T., Bueno-De-Mesquita, H.B., Peeters, P.H.M., Trichopoulou, A., Linseisen, J., Boeing, H., Hallmans, G., Overvad, K., Tjønneland, A., Kumle, M., Riboli, E., Mckay, Jd, Hung, Rj, Gaborieau, V, Boffetta, P, Chabrier, A, Byrnes, G, Zaridze, D, Mukeria, A, Szeszenia Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Mates, D, Bencko, V, Foretova, L, Janout, V, Mclaughlin, J, Shepherd, F, Montpetit, A, Narod, S, Krokan, He, Skorpen, F, Elvestad, Mb, Vatten, L, Njølstad, I, Axelsson, T, Chen, C, Goodman, G, Barnett, M, Loomis, Mm, Lubiñski, J, Matyjasik, J, Lener, M, Oszutowska, D, Field, J, Liloglou, T, Xinarianos, G, Cassidy, A, Epic, Study, Vineis, P, Clavel Chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, Salvatore, González, Ca, Ramón Quirós, J, Martínez, C, Navarro, C, Ardanaz, E, Larrañaga, N, Kham, Kt, Key, T, Bueno de Mesquita, Hb, Peeters, Ph, Trichopoulou, A, Linseisen, J, Boeing, H, Hallmans, G, Overvad, K, Tjønneland, A, Kumle, M, Riboli, E, Zelenika, D, Boland, A, Delepine, M, Foglio, M, Lechner, D, Matsuda, F, Blanche, H, Gut, I, Heath, S, and Lathrop, M

Subjects
Lung Neoplasms, Locus (genetics), Genome-wide association study, Apoptosis, Biology, Article, Genetics, medicine, Humans, Genetic Predisposition to Disease, Lung cancer, Gene, Telomerase, Principal Component Analysis, Respiratory disease, Smoking, Case-control study, Cancer, Membrane Proteins, medicine.disease, Lung cancer susceptibility, Molecular biology, Neoplasm Proteins, Case-Control Studies, Immunology, Chromosomes, Human, Pair 5, Genome-Wide Association Study
Abstract

We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P = 2 × 10-7 and P = 4 × 10-6) and replicated by the independent study series (P = 7 × 10-5 and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology. © 2008 Nature Publishing Group.

Published
2008

15. Deep sequencing of the trypanosoma cruzi GP63 surface proteases reveals diversity and diversifying selection among chronic and congenital Chagas disease patients

Author

Llewellyn, M.S., Messenger, L.A., Luquetti, A.O., Garcia, L., Torrico, F., Tavares, S.B.N., Cheaib, B., Derome, N., Delepine, M., Baulard, C., Deleuze, J.-F., Sauer, S., and Miles, M.A.

Subjects
Technology Platforms
Abstract

Background\ud \ud Chagas disease results from infection with the diploid protozoan parasite Trypanosoma cruzi. T. cruzi is highly genetically diverse, and multiclonal infections in individual hosts are common, but little studied. In this study, we explore T. cruzi infection multiclonality in the context of age, sex and clinical profile among a cohort of chronic patients, as well as paired congenital cases from Cochabamba, Bolivia and Goias, Brazil using amplicon deep sequencing technology.\ud \ud Methodology/ Principal Findings\ud \ud A 450bp fragment of the trypomastigote TcGP63I surface protease gene was amplified and sequenced across 70 chronic and 22 congenital cases on the Illumina MiSeq platform. In addition, a second, mitochondrial target—ND5—was sequenced across the same cohort of cases. Several million reads were generated, and sequencing read depths were normalized within patient cohorts (Goias chronic, n = 43, Goias congenital n = 2, Bolivia chronic, n = 27; Bolivia congenital, n = 20), Among chronic cases, analyses of variance indicated no clear correlation between intra-host sequence diversity and age, sex or symptoms, while principal coordinate analyses showed no clustering by symptoms between patients. Between congenital pairs, we found evidence for the transmission of multiple sequence types from mother to infant, as well as widespread instances of novel genotypes in infants. Finally, non-synonymous to synonymous (dn:ds) nucleotide substitution ratios among sequences of TcGP63Ia and TcGP63Ib subfamilies within each cohort provided powerful evidence of strong diversifying selection at this locus.\ud \ud Conclusions/Significance\ud \ud Our results shed light on the diversity of parasite DTUs within each patient, as well as the extent to which parasite strains pass between mother and foetus in congenital cases. Although we were unable to find any evidence that parasite diversity accumulates with age in our study cohorts, putative diversifying selection within members of the TcGP63I gene family suggests a link between genetic diversity within this gene family and survival in the mammalian host.

Published
2015

16. A genome-wide association study of upperaerodigestive tract cancers conducted within the INHANCE consortium

Author

McKay JD, Truong T, Gaborieau V, Chabrier A, Chuang SC, Byrnes G, Zaridze D, Shangina O, Szeszenia Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Bucur A, Bencko V, Holcatova I, Janout V, Foretova L, Lagiou P, Trichopoulos D, Benhamou S, Bouchardy C, Ahrens W, Merletti F, Richiardi L, Talamini R, Barzan L, Kjaerheim K, Macfarlane GJ, Macfarlane TV, Simonato L, Canova C, Agudo A, Castellsagué X, Lowry R, Conway DI, McKinney PA, Healy CM, Toner ME, Znaor A, Curado MP, Koifman S, Menezes A, Wünsch Filho V, Neto JE, Garrote LF, Boccia S, Cadoni G, Arzani D, Olshan AF, Weissler MC, Funkhouser WK, Luo J, Lubiński J, Trubicka J, Lener M, Oszutowska D, Schwartz SM, Chen C, Fish S, Doody DR, Muscat JE, Lazarus P, Gallagher CJ, Chang SC, Zhang ZF, Wei Q, Sturgis EM, Wang LE, Franceschi S, Herrero R, Kelsey KT, McClean MD, Marsit CJ, Nelson HH, Romkes M, Buch S, Nukui T, Zhong S, Lacko M, Manni JJ, Peters WH, Hung RJ, McLaughlin J, Vatten L, Njølstad I, Goodman GE, Field JK, Liloglou T, Vineis P, Clavel Chapelon F, Palli D, Tumino R, Krogh V, González CA, Quirós JR, Martínez C, Navarro C, Ardanaz E, Larrañaga N, Khaw KT, Key T, Bueno de Mesquita HB, Peeters PH, Trichopoulou A, Linseisen J, Boeing H, Hallmans G, Overvad K, Tjønneland A, Kumle M, Riboli E, Välk K, Vooder T, Metspalu A, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Blanché H, Gut IG, Galan P, Heath S, Hashibe M, Hayes RB, Boffetta P, Lathrop M, Brennan P., PANICO, SALVATORE, Mckay, Jd, Truong, T, Gaborieau, V, Chabrier, A, Chuang, Sc, Byrnes, G, Zaridze, D, Shangina, O, Szeszenia Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Bucur, A, Bencko, V, Holcatova, I, Janout, V, Foretova, L, Lagiou, P, Trichopoulos, D, Benhamou, S, Bouchardy, C, Ahrens, W, Merletti, F, Richiardi, L, Talamini, R, Barzan, L, Kjaerheim, K, Macfarlane, Gj, Macfarlane, Tv, Simonato, L, Canova, C, Agudo, A, Castellsagué, X, Lowry, R, Conway, Di, Mckinney, Pa, Healy, Cm, Toner, Me, Znaor, A, Curado, Mp, Koifman, S, Menezes, A, Wünsch Filho, V, Neto, Je, Garrote, Lf, Boccia, S, Cadoni, G, Arzani, D, Olshan, Af, Weissler, Mc, Funkhouser, Wk, Luo, J, Lubiński, J, Trubicka, J, Lener, M, Oszutowska, D, Schwartz, Sm, Chen, C, Fish, S, Doody, Dr, Muscat, Je, Lazarus, P, Gallagher, Cj, Chang, Sc, Zhang, Zf, Wei, Q, Sturgis, Em, Wang, Le, Franceschi, S, Herrero, R, Kelsey, Kt, Mcclean, Md, Marsit, Cj, Nelson, Hh, Romkes, M, Buch, S, Nukui, T, Zhong, S, Lacko, M, Manni, Jj, Peters, Wh, Hung, Rj, Mclaughlin, J, Vatten, L, Njølstad, I, Goodman, Ge, Field, Jk, Liloglou, T, Vineis, P, Clavel Chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, Salvatore, González, Ca, Quirós, Jr, Martínez, C, Navarro, C, Ardanaz, E, Larrañaga, N, Khaw, Kt, Key, T, Bueno de Mesquita, Hb, Peeters, Ph, Trichopoulou, A, Linseisen, J, Boeing, H, Hallmans, G, Overvad, K, Tjønneland, A, Kumle, M, Riboli, E, Välk, K, Vooder, T, Metspalu, A, Zelenika, D, Boland, A, Delepine, M, Foglio, M, Lechner, D, Blanché, H, Gut, Ig, Galan, P, Heath, S, Hashibe, M, Hayes, Rb, Boffetta, P, Lathrop, M, and Brennan, P.

Published
2011

17. Mutations activatrices de mTOR en mosaïque dans l’hypomélanose d’Ito avec mégalencéphalie

Author

Vabres, P., primary, Parker, V., additional, Courcet, J.-B., additional, St-Onge, J., additional, Duffourd, Y., additional, Rodriguez, D., additional, Mignot, C., additional, Knox, R., additional, Boland, A., additional, Olaso, R., additional, Delepine, M., additional, Darmency-Stamboul, V., additional, Vincent-Delorme, C., additional, Catteau, B., additional, Guibaud, L., additional, Arzimanoglou, A., additional, Keddar, M., additional, Callier, P., additional, Bessis, D., additional, Geneviève, D., additional, Deleuze, J.-F., additional, Semple, R., additional, Faivre, L., additional, and Rivière, J.-B., additional

Published
2015
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18. Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders

Author

State, M., Leblond, C.S., Heinrich, J., Delorme, R., Proepper, C., Betancur, C., Huguet, G., Konyukh, M., Chaste, P., Ey, E., Rastam, M., Anckarsäter, H., Nygren, G., Gillberg, I.C., Melke, J., Toro, R., Regnault, B., Fauchereau, F., Mercati, O., Lemière, N., Skuse, D., Poot, M., Holt, R., Monaco, A.P., Järvelä, I., Kantojärvi, K., Vanhala, R., Curran, S., Collier, D.A., Bolton, P., Chiocchetti, A., Klauck, S.M., Poustka, F., Freitag, C.M., Waltes, R., Kopp, M., Duketis, E., Bacchelli, E., Minopoli, F., Ruta, L., Battaglia, A., Mazzone, L., Maestrini, E., Sequeira, A.F., Oliveira, B., Vicente, A., Oliveira, G., Pinto, D., Scherer, S.W., Zelenika, D., Delepine, M., Lathrop, M., Bonneau, D., Guinchat, V., Devillard, F., Assouline, B., Mouren, M., Leboyer, M., Gillberg, C., Boeckers, T.M., and Bourgeron, T.

Subjects
mental disorders
Abstract

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

Published
2012

19. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer’s disease

Author

Lambert, J. C., Grenier-Boley, B., Harold, D., Zelenika, D., Chouraki, V., Kamatani, Y., Sleegers, K., Ikram, M.A., Hiltunen, M., Reitz, Christiane, Mateo, I., Feulner, T., Bullido, M., Galimberti, D., Concari, L., Alvarez, V., Sims, R., Gerrish, A., Chapman, J., Deniz-Naranjo, C., Solfrizzi, V., Sorbi, S., Arosio, B., Spalletta, G., Siciliano, G., Epelbaum, J., Hannequin, D., Dartigues, J. F., Tzourio, C., Berr, C., Schrijvers, E. M. C., Rogers, R., Tosto, Giuseppe, Pasquier, F., Bettens, K., Van Cauwenberghe, C., Fratiglioni, L., Graff, C., Delepine, M., Ferri, R., Reynolds, C. A., Lannfelt, L., Ingelsson, M., Prince, J. A., Pilotto, A., Chillotti, C., Seripa, D., Boland, A., Mancuso, M., Bossu, P., Annoni, G., Nacmias, B., Bosco, P., Panza, F., Sanchez-Garcia, F., Del Zompo, M., Coto, E., Owen, M., Valdivieso, F., O'Donovan, M., Caffara, P., Scarpini, E., Campion, D., Buee, L., Combarros, O., Soininen, H., Breteler, M., Riemenschneider, M., Van Broeckhoven, C., Alperovitch, A., Williams, J., Lathrop, M., Tregouet, D. A., Amouyel, P., EADI Consortium, and GERAD Consortium

Subjects
Molecular biology, FOS: Biological sciences, Genetics, Psychobiology
Abstract

Recently, several genome-wide association studies (GWASs) have led to the discovery of nine new loci of genetic susceptibility in Alzheimer's disease (AD). However, the landscape of the AD genetic susceptibility is far away to be complete and in addition to single-SNP (single-nucleotide polymorphism) analyses as performed in conventional GWAS, complementary strategies need to be applied to overcome limitations inherent to this type of approaches. We performed a genome-wide haplotype association (GWHA) study in the EADI1 study (n=2025 AD cases and 5328 controls) by applying a sliding-windows approach. After exclusion of loci already known to be involved in AD (APOE, BIN1 and CR1), 91 regions with suggestive haplotype effects were identified. In a second step, we attempted to replicate the best suggestive haplotype associations in the GERAD1 consortium (2820 AD cases and 6356 controls) and observed that 9 of them showed nominal association. In a third step, we tested relevant haplotype associations in a combined analysis of five additional case–control studies (5093 AD cases and 4061 controls). We consistently replicated the association of a haplotype within FRMD4A on Chr.10p13 in all the data set analyzed (OR: 1.68; 95% CI: (1.43–1.96); P=1.1 × 10−10). We finally searched for association between SNPs within the FRMD4A locus and Aβ plasma concentrations in three independent non-demented populations (n=2579). We reported that polymorphisms were associated with plasma Aβ42/Aβ40 ratio (best signal, P=5.4 × 10−7). In conclusion, combining both GWHA study and a conservative three-stage replication approach, we characterised FRMD4A as a new genetic risk factor of AD.

Published
2012
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20. LARGE-SCALE TEST OF HYPOTHESISED ASSOCIATIONS BETWEEN POLYMORPHISM OF LIPID-RELATED GENES AND MYOCARDIAL INFARCTION IN ABOUT 5000 CASES AND 6000 CONTROLS

Author

Keavney, B, Youngman, L, Palmer, A, Parish, S, Clark, S, Delepine, M, Lathrop, M, Peto, R, and Collins, R

Subjects
Heart diseases -- Risk factors -- Genetic aspects, Coronary heart disease -- Risk factors -- Genetic aspects, Risk factors (Health) -- Genetic aspects -- Health aspects, Genetic polymorphisms -- Health aspects -- Genetic aspects, Blood lipids -- Genetic aspects -- Health aspects, Health, Genetic aspects, Risk factors, Health aspects
Abstract

M Delepine [1] M Lathrop [1] Background: Some relatively small studies have reported associations between the risk of myocardial infarction (MI) and genotypes at polymorphism of genes related to blood [...]

Published
2001

21. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium

Author

Horwitz, M.S., McKay, J.D., Truong, T., Gaborieau, V., Chabrier, A., Chuang, S.-C., Byrnes, G., Zaridze, D., Shangina, O., Szeszenia-Dabrowska, N., Lissowska, J., Rudnai, P., Fabianova, E., Bucur, A., Bencko, V., Holcatova, I., Janout, V., Foretova, L., Lagiou, P., Trichopoulos, D., Benhamou, S., Bouchardy, C., Ahrens, W., Merletti, F., Richiardi, L., Talamini, R., Barzan, L., Kjaerheim, K., Macfarlane, G.J., Macfarlane, T.V., Simonato, L., Canova, C., Agudo, A., Castellsagué, X., Lowry, R., Conway, D.I., McKinney, P.A., Healy, C.M., Toner, M.E., Znaor, A., Curado, M.P., Koifman, S., Menezes, A., Wünsch-Filho, V., Neto, J.E., Garrote, L.F., Boccia, S., Cadoni, G., Arzani, D., Olshan, A.F., Weissler, M.C., Funkhouser, W.K., Luo, J., Lubiński, J., Trubicka, J., Lener, M., Oszutowska, D., Schwartz, S.M., Chen, C., Fish, S., Doody, D.R., Muscat, J.E., Lazarus, P., Gallagher, C.J., Chang, S.C., Zhang, Z.F., Wei, Q., Sturgis, E.M., Wang, L.E., Franceschi, S., Herrero, R., Kelsey, K.T., McClean, M.D., Marsit, C.J., Nelson, H.H., Romkes, M., Buch, S., Nukui, T., Zhong, S., Lacko, M., Manni, J.J., Peters, W.H.M., Hung, R.J., McLaughlin, J., Vatten, L., Njølstad, I., Goodman, G.E., Field, J.K., Liloglou, T., Vineis, P., Clavel-Chapelon, F., Palli, D., Tumino, R., Krogh, V., Panico, S., González, C.A., Quirós, J.R., Martínez, C., Navarro, C., Ardanaz, E., Larrañaga, N., Khaw, K.T., Key, T., Bueno-de-Mesquita, H. B., Peeters, P.H.M., Trichopoulou, A., Linseisen, J., Boeing, H., Hallmans, G., Overvad, K., Tjønneland, A., Kumle, M., Riboli, E., Välk, K., Vooder, T., Metspalu, A., Zelenika, D., Boland, A., Delepine, M., Foglio, M., Lechner, D., Blanché, H., Gut, I.G., Galan, P., Heath, S., Hashibe, M., Hayes, R.B., Boffetta, P., Lathrop, M., and Brennan, P.

Abstract

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p≤5×10−7). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10−8) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2×10−8) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5×10−8; rs1229984-ADH1B, p = 7×10−9; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Published
2011

22. The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study

Author

Lambert, J., Sleegers, K., Gonzalez-Perez, A., Ingelsson, M., Beecham, G., Hiltunen, M., Combarros, O., Bullido, M., Brouwers, N., Bettens, K., Berr, C., Pasquier, F., Richard, F., Dekosky, S., Hannequin, D., Haines, J., Tognoni, G., Fievet, N., Dartigues, J., Tzourio, C., Engelborghs, S., Arosio, B., Coto, E., De Deyn, P., Del Zompo, M., Mateo, I., Boada, M., Antunez, C., Lopez-Arrieta, J., Epelbaum, J., Schjeide, B., Frank-Garcia, A., Giedraitis, V., Helisalmi, S., Porcellini, E., Pilotto, A., Forti, P., Ferri, R., Delepine, M., Zelenika, D., Lathrop, M., Scarpini, E., Siciliano, G., Solfrizzi, V., Sorbi, S., Spalletta, G., Ravaglia, G., Valdivieso, F., Vepsalainen, S., Alvarez, V., Bosco, P., Mancuso, M., Panza, F., Nacmias, B., Bossu, P., Hanon, O., Piccardi, P., Annoni, G., Mann, D., Marambaud, P., Seripa, D., Galimberti, D., Tanzi, R., Bertram, L., Lendon, C., Lannfelt, L., Licastro, F., Campion, D., Pericak-Vance, M., Soininen, H., Van Broeckhoven, C., Alperovitch, A., Ruiz, A., Kamboh, M., and Amouyel, P.

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the epsilon4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the epsilon4 allele of the APOE gene.

Published
2010

23. Genetic analysis of chromosome 2 in type 1 diabetes. Analysis of putative loci IDDM7, IDDM12 and IDDM13 and candidate genes NRAMP1 and IA-2 and the inteleukin-1 gene cluster

Author

Esposito L, Hill NJ, Pritchard LE, Cucca F, Muxworthy C, Merriman ME, Wilson A, Julier C, Delepine M, Tuomilehto J, Tuomilehto Wolf E, Ionesco Tirgoviste C, Nisticò L, IMDIAB Group, Buzzetti R, Pozzilli P, FERRARI, MAURIZIO, Pociot F, Nerup J, Bain SC, Todd JA, BOSI , EMANUELE, Esposito, L, Hill, Nj, Pritchard, Le, Cucca, F, Muxworthy, C, Merriman, Me, Wilson, A, Julier, C, Delepine, M, Tuomilehto, J, Tuomilehto Wolf, E, Ionesco Tirgoviste, C, Nisticò, L, Imdiab, Group, Buzzetti, R, Pozzilli, P, Ferrari, Maurizio, Bosi, Emanuele, Pociot, F, Nerup, J, Bain, Sc, and Todd, Ja

Published
1998

24. Lung cancer susceptibility locus at 5p15.33

Author

McKay, J.D. Hung, R.J. Gaborieau, V. Boffetta, P. Chabrier, A. Byrnes, G. Zaridze, D. Mukeria, A. Szeszenia-Dabrowska, N. Lissowska, J. Rudnai, P. Fabianova, E. Mates, D. Bencko, V. Foretova, L. Janout, V. McLaughlin, J. Shepherd, F. Montpetit, A. Narod, S. Krokan, H.E. Skorpen, F. Elvestad, M.B. Vatten, L. Njølstad, I. Axelsson, T. Chen, C. Goodman, G. Barnett, M. Loomis, M.M. Lubĩski, J. Matyjasik, J. Lener, M. Oszutowska, D. Field, J. Liloglou, T. Xinarianos, G. Cassidy, A. Zelenika, D. Boland, A. Delepine, M. Foglio, M. Lechner, D. Matsuda, F. Blanche, H. Gut, I. Heath, S. Lathrop, M. Brennan, P. Vineis, P. Clavel-Chapelon, F. Palli, D. Tumino, R. Krogh, V. Panico, S. González, C.A. Ramón Quirós, J. Martínez, C. Navarro, C. Ardanaz, E. Larrãaga, N. Kham, K.T. Key, T. Bueno-De-Mesquita, H.B. Peeters, P.H.M. Trichopoulou, A. Linseisen, J. Boeing, H. Hallmans, G. Overvad, K. Tjønneland, A. Kumle, M. Riboli, E.

Abstract

We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P = 2 × 10-7 and P = 4 × 10-6) and replicated by the independent study series (P = 7 × 10-5 and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology. © 2008 Nature Publishing Group.

Published
2008

26. Wolcott-Rallison syndrome - Clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity

Author

Senee, V, Vattem, KM, Delepine, M, Rainbow, LA, Haton, C, Lecoq, A, Shaw, NJ, and Çukurova Üniversitesi

Abstract

WOS: 000222397000030 PubMed ID: 15220213 Wolcott-Rallison syndrome (WRS) is a rare autosomal-recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple epiphyseal dysplasia and growth retardation, and other variable multisystemic clinical manifestations. Based on genetic studies of two inbred families, we previously identified the gene responsible for this disorder as EIF2AK3, the pancreatic eukaryotic initiation factor 2alpha (eIF2alpha) kinase. Here, we have studied 12 families with WRS, totalling 18 cases. With the exception of one case, all patients carried EIF2AK3 mutations resulting in truncated or missense versions of the protein. Exclusion of EIF2AK3 mutations in the one patient case was confirmed by both linkage and sequence data. The activities of missense versions of EIF2AK3 were characterized in vivo and in vitro and found to have a complete lack of activity in four mutant proteins and residual kinase activity in one. Remarkably, the onset of diabetes was relatively late (30 months) in the patient expressing the partially defective EIF2AK3 mutant and in the patient with no EIF2AK3 involvement (18 months) compared with other patients (

Published
2004

27. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease

Author

Lambert, JC, Grenier-Boley, B, Harold, D, Zelenika, D, Chouraki, V, Kamatani, Y, Sleegers, K (Kristel), Ikram, Arfan, Hiltunen, M, Reitz, C, Mateo, I, Feulner, T, Bullido, M, Galimberti, D, Concari, L, Alvarez, V, Sims, R, Gerrish, A, Chapman, J, Deniz-Naranjo, C, Solfrizzi, V, Sorbi, S, Arosio, B, Spalletta, G, Siciliano, G, Epelbaum, J, Hannequin, D, Dartigues, JF, Tzourio, C, Berr, C, Schrijvers, Elisabeth, Rogers, R, Tosto, G, Pasquier, F, Bettens, K, Van Cauwenberghe, C, Fratiglioni, L, Graff, C, Delepine, M, Ferri, R, Reynolds, CA, Lannfelt, L, Ingelsson, M, Prince, JA, Chillotti, C, Pilotto, A, Seripa, D, Boland, A, Mancuso, M, Bossu, P, Annoni, G, Nacmias, B, Bosco, P, Panza, F, Sanchez-Garcia, F, Del Zompo, M, Coto, E, Owen, M, O'Donovan, M, Valdivieso, F, Caffara, P, Scarpini, E, Combarros, O, Buee, L, Campion, D, Soininen, H, Breteler, Monique, Riemenschneider, M, van Broeckhoven, C, Alperovitch, A, Lathrop, M, Tregouet, DA, Williams, J, Amouyel, P, Lambert, JC, Grenier-Boley, B, Harold, D, Zelenika, D, Chouraki, V, Kamatani, Y, Sleegers, K (Kristel), Ikram, Arfan, Hiltunen, M, Reitz, C, Mateo, I, Feulner, T, Bullido, M, Galimberti, D, Concari, L, Alvarez, V, Sims, R, Gerrish, A, Chapman, J, Deniz-Naranjo, C, Solfrizzi, V, Sorbi, S, Arosio, B, Spalletta, G, Siciliano, G, Epelbaum, J, Hannequin, D, Dartigues, JF, Tzourio, C, Berr, C, Schrijvers, Elisabeth, Rogers, R, Tosto, G, Pasquier, F, Bettens, K, Van Cauwenberghe, C, Fratiglioni, L, Graff, C, Delepine, M, Ferri, R, Reynolds, CA, Lannfelt, L, Ingelsson, M, Prince, JA, Chillotti, C, Pilotto, A, Seripa, D, Boland, A, Mancuso, M, Bossu, P, Annoni, G, Nacmias, B, Bosco, P, Panza, F, Sanchez-Garcia, F, Del Zompo, M, Coto, E, Owen, M, O'Donovan, M, Valdivieso, F, Caffara, P, Scarpini, E, Combarros, O, Buee, L, Campion, D, Soininen, H, Breteler, Monique, Riemenschneider, M, van Broeckhoven, C, Alperovitch, A, Lathrop, M, Tregouet, DA, Williams, J, and Amouyel, P

Published
2013

28. Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

Author

Lambert, J, Zelenika, D, Hiltunen, M, Chouraki, V, Combarros, O, Bullido, M, Tognoni, G, Fiévet, N, Boland, A, Arosio, B, Coto, E, Zompo, M, Mateo, I, Frank Garcia, A, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Delepine, M, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Ravaglia, G, Valdivieso, F, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Licastro, F, Lathrop, M, Soininen, H, Amouyel, P, Bullido, MJ, Zompo, MD, ANNONI, GIORGIO, Amouyel, P., Lambert, J, Zelenika, D, Hiltunen, M, Chouraki, V, Combarros, O, Bullido, M, Tognoni, G, Fiévet, N, Boland, A, Arosio, B, Coto, E, Zompo, M, Mateo, I, Frank Garcia, A, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Delepine, M, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Ravaglia, G, Valdivieso, F, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Licastro, F, Lathrop, M, Soininen, H, Amouyel, P, Bullido, MJ, Zompo, MD, ANNONI, GIORGIO, and Amouyel, P.

Abstract

Recent genome-wide association studies have identified 5 loci (BIN1, CLU, CR1, EXOC3L2, and PICALM) as genetic determinants of Alzheimer's disease (AD). We attempted to confirm the association between these genes and the AD risk in 3 contrasting European populations (from Finland, Italy, and Spain). Because CLU and CR1 had already been analyzed in these populations, we restricted our investigation to BIN1, EXO2CL3, and PICALM. In a total of 2816 AD cases and 2706 controls, we unambiguously replicated the association of rs744373 (for BIN1) and rs541458 (for PICALM) polymorphisms with the AD risk (odds ratio [OR] = 1.26, 95% confidence interval [CI] [1.15-1.38], p = 2.9 × 10-7, and OR = 0.80, 95% CI [0.74-0.88], p = 4.6 × 10-7, respectively). In a meta-analysis, rs597668 (EXOC3L2) was also associated with the AD risk, albeit to a lesser extent (OR = 1.19, 95% CI [1.06-1.32], p = 2.0 × 10-3). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN1 and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation. © 2011 Elsevier Inc.

Published
2011

29. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

Author

Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J, Carrasquillo, M, Abraham, R, Hamshere, M, Pahwa, J, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, M, Brayne, C, Rubinsztein, D, Gill, M, Lawlor, B, Lynch, A, Brown, K, Passmore, P, Craig, D, Mcguinness, B, Todd, S, Holmes, C, Mann, D, Smith, A, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, P, Hooper, N, Vardy, E, Hardy, J, Mead, S, Fox, N, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, A, Kauwe, J, Cruchaga, C, Nowotny, P, Morris, J, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, P, Van Broeckhoven, C, Livingston, G, Bass, N, Gurling, H, Mcquillin, A, Gwilliam, R, Deloukas, P, Al Chalabi, A, Shaw, C, Tsolaki, M, Singleton, A, Guerreiro, R, Mühleisen, T, Nöthen, M, Moebus, S, Jöckel, K, Klopp, N, Wichmann, H, Pankratz, V, Sando, S, Aasly, J, Barcikowska, M, Wszolek, Z, Dickson, D, Graff Radford, N, Petersen, R, van Duijn, C, Breteler, M, Ikram, M, Destefano, A, Fitzpatrick, A, Lopez, O, Launer, L, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, T, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, Snædal, J, Björnsson, S, Jonsson, P, Chouraki, V, Genier Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, M, Pasquier, F, Mateo, I, Frank Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, P, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, S, Owen, M, O'Donovan, M, Amouyel, P, Williams, J, Carrasquillo, MM, Hamshere, ML, Pahwa, JS, Lupton, MK, Rubinsztein, DC, Brown, KS, Passmore, PA, McGuinness, B, Smith, AD, Kehoe, PG, Hooper, NM, Vardy, ERLC, Fox, NC, Goate, AM, Kauwe, JSK, Morris, JC, De Deyn, PP, Bass, NJ, McQuillin, A, Shaw, CE, Singleton, AB, Mühleisen, TW, Nöthen, MM, Pankratz, VS, Sando, SB, Aasly, JO, Wszolek, ZK, Dickson, DW, Graff Radford, NR, Petersen, RC, van Duijn, CM, Breteler, MMB, Ikram, MA, DeStefano, AL, Fitzpatrick, AL, Launer, LJ, Feulner, TM, Jonsson, PV, Bullido, MJ, ANNONI, GIORGIO, Holmans, PA, Younkin, SG, Owen, MJ, Williams, J., Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J, Carrasquillo, M, Abraham, R, Hamshere, M, Pahwa, J, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, M, Brayne, C, Rubinsztein, D, Gill, M, Lawlor, B, Lynch, A, Brown, K, Passmore, P, Craig, D, Mcguinness, B, Todd, S, Holmes, C, Mann, D, Smith, A, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, P, Hooper, N, Vardy, E, Hardy, J, Mead, S, Fox, N, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, A, Kauwe, J, Cruchaga, C, Nowotny, P, Morris, J, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, P, Van Broeckhoven, C, Livingston, G, Bass, N, Gurling, H, Mcquillin, A, Gwilliam, R, Deloukas, P, Al Chalabi, A, Shaw, C, Tsolaki, M, Singleton, A, Guerreiro, R, Mühleisen, T, Nöthen, M, Moebus, S, Jöckel, K, Klopp, N, Wichmann, H, Pankratz, V, Sando, S, Aasly, J, Barcikowska, M, Wszolek, Z, Dickson, D, Graff Radford, N, Petersen, R, van Duijn, C, Breteler, M, Ikram, M, Destefano, A, Fitzpatrick, A, Lopez, O, Launer, L, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, T, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, Snædal, J, Björnsson, S, Jonsson, P, Chouraki, V, Genier Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, M, Pasquier, F, Mateo, I, Frank Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, P, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, S, Owen, M, O'Donovan, M, Amouyel, P, Williams, J, Carrasquillo, MM, Hamshere, ML, Pahwa, JS, Lupton, MK, Rubinsztein, DC, Brown, KS, Passmore, PA, McGuinness, B, Smith, AD, Kehoe, PG, Hooper, NM, Vardy, ERLC, Fox, NC, Goate, AM, Kauwe, JSK, Morris, JC, De Deyn, PP, Bass, NJ, McQuillin, A, Shaw, CE, Singleton, AB, Mühleisen, TW, Nöthen, MM, Pankratz, VS, Sando, SB, Aasly, JO, Wszolek, ZK, Dickson, DW, Graff Radford, NR, Petersen, RC, van Duijn, CM, Breteler, MMB, Ikram, MA, DeStefano, AL, Fitzpatrick, AL, Launer, LJ, Feulner, TM, Jonsson, PV, Bullido, MJ, ANNONI, GIORGIO, Holmans, PA, Younkin, SG, Owen, MJ, and Williams, J.

Abstract

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ĝ‰Currency sign 1 × 10 -5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10 -17; including ADGC data, meta P = 5.0 × 10 -21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10 -14; including ADGC data, meta P = 1.2 × 10 -16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10 -4; including ADGC data, meta P = 8.6 × 10 -9), CD33 (GERAD+, P = 2.2 × 10 -4; including ADGC data, meta P = 1.6 × 10 -9) and EPHA1 (GERAD+, P = 3.4 × 10 -4; including ADGC data, meta P = 6.0 × 10 -10). © 2011 Nature America, Inc. All rights reserved.

Published
2011

34. Multiple DNA Variant Association Analysis: Application to the Insulin Gene Region in Type 1 Diabetes

Author

Julier, C., Lucassen, A., Villedieu, P., Delepine, M., Levy-Marchal, C., Danzé, P. M., Bianchi, F., Boitard, C., Froguel, P., Bell, J., and Lathrop, G. M.

Subjects
Molecular Epidemiology, Diabetes Mellitus, Type 1, Genetic Variation, Humans, Insulin, Original Articles, Disease Susceptibility, France
Abstract

Association and linkage studies have shown that at least one of the genetic factors involved in susceptibility to insulin-dependent diabetes mellitus (IDDM) is contained within a 4.1-kb region of the insulin gene. Sequence analysis has led to the identification of 10 DNA variants in this region that are associated with increased risk for IDDM. These variants are in strong linkage disequilibrium with each other, and previous studies have failed to distinguish between the variant(s) that cause increased susceptibility to IDDM and others that are associated with the disease because of linkage disequilibrium. To address this problem, we have undertaken a large population study of French diabetics and controls and have analyzed genotype patterns for several of the variant sites simultaneously. This has led to the identification of a subset consisting of four variants (-2733AC, -23HphI, -365VNTR, and +1140AC), at least one of which appears to be directly implicated in disease susceptibility. The multiple-DNA-variant association-analysis approach that is applied here to the problem of identifying potential susceptibility variants in IDDM is likely to be important in studies of many other multifactorial diseases.

Published
1994

36. Genetic analysis of chromosome 2 in type 1 diabetes: analysis of putative loci IDDM7, IDDM12, and IDDM13 and candidate genes NRAMP1 and IA-2 and the interleukin-1 gene cluster. IMDIAB Group.

Author

Esposito, L, primary, Hill, N J, additional, Pritchard, L E, additional, Cucca, F, additional, Muxworthy, C, additional, Merriman, M E, additional, Wilson, A, additional, Julier, C, additional, Delepine, M, additional, Tuomilehto, J, additional, Tuomilehto-Wolf, E, additional, Ionesco-Tirgoviste, C, additional, Nistico', L, additional, Buzzetti, R, additional, Pozzilli, P, additional, Ferrari, M, additional, Bosi, E, additional, Pociot, F, additional, Nerup, J, additional, Bain, S C, additional, and Todd, J A, additional

Published
1998
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37. Genetic Susceptibility for Human Familial Essential Hypertension in a Region of Homology with Blood Pressure Linkage on Rat Chromosome 10

Author

Julier, C., primary, Delepine, M., additional, Keavney, B., additional, Terwilliger, J., additional, Davis, S., additional, Weeks, D. E., additional, Bui, T., additional, Jeunemaitre, X., additional, Velho, G., additional, Froguel, P., additional, Ratcliffe, P., additional, Corvol, P., additional, Soubrier, F., additional, and Mark Lathrop, G., additional

Published
1997
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38. Genetic mapping of a susceptibility locus for insulin-dependent diabetes mellitus on chromosome llq

Author

Hashimoto, L., primary, Habita, C., additional, Beressi, J. P., additional, Delepine, M., additional, Basse, C., additional, Cambon-Thomsen, A., additional, Deschamps, I., additional, Rotter, J. I., additional, Djoulah, S., additional, James, M. R., additional, Froguel, P., additional, Weissenbach, J., additional, Lathrop, G. M., additional, and Julier, C., additional

Published
1994
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44. Organic matter in phosphates: identification and impact on the roasting operation.

Author

Delepine M., Dokhri H., Hassani E.A., Lahlou F., Delepine M., Dokhri H., Hassani E.A., and Lahlou F.

Abstract

The modifications of behaviour of the mineral phases in the presence of organic matter are linked to the reductive action induced by the products of degradation of these substances. This action is illustrated by the reduction and the volatilisation of cadmium, and the reduction of the sulphate groupings of apatite., The modifications of behaviour of the mineral phases in the presence of organic matter are linked to the reductive action induced by the products of degradation of these substances. This action is illustrated by the reduction and the volatilisation of cadmium, and the reduction of the sulphate groupings of apatite.

46. Pilot roasting tests of the black phosphates by different processes.

Author

Hassani E.A., Benkirane M.G., Delepine M., Rhofir A., Hassani E.A., Benkirane M.G., Delepine M., and Rhofir A.

Abstract

The results of pilot tests using the following processes are discussed: drying and flash roasting; flash roasting in several cyclone stages; roasting in a fluidised bed; and roasting in a circulating fluidised bed., The results of pilot tests using the following processes are discussed: drying and flash roasting; flash roasting in several cyclone stages; roasting in a fluidised bed; and roasting in a circulating fluidised bed.

48. Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

Author

Lacombe Didier, Mom Thierry, Francannet Christine, Duvillard Alain, Thauvin Christel, Dubin Jacques, Bonneau Dominique, Montaut-Verient Bettina, Vigneron Jacqueline, Calais Catherine, David Albert, Eliot Marie-Madeleine, Dollfus Hélène, Vincent Christophe, Delobel Bruno, Weil Dominique, El-Amraoui Aziz, Jonard Laurence, Feldmann Delphine, Zelenika Diana, Délépine Marc, Niasme-Grare Magali, Parodi Marine, Hardelin Jean-Pierre, Levilliers Jacqueline, Marlin Sandrine, Grati M'hamed, Bonnet Crystel, Duriez Françoise, Drouin-Garraud Valérie, Thuillier-Obstoy Marie-Françoise, Sigaudy Sabine, Frances Anne-Marie, Collignon Patrick, Challe Georges, Couderc Rémy, Lathrop Mark, Sahel José-Alain, Weissenbach Jean, Petit Christine, and Denoyelle Françoise

Subjects
Medicine
Abstract

Abstract Background Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. Methods We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). Results Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. Conclusions Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.

Published
2011
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49. Common Variants at Abca7, Ms4A6A/Ms4A4E, Epha1, Cd33 and Cd2Ap Are Associated with Alzheimer'S Disease

Author

Neill R. Graff-Radford, Caroline S. Widdowson, John Hardy, Simon Lovestone, Stefan Schreiber, Ana Frank-García, Amy Gerrish, Kevin Mayo, Alexandra Stretton, Michael John Owen, Minerva M. Carrasquillo, Seth Love, Jade Chapman, Vincent Chouraki, Monique M.B. Breteler, Francesco Panza, Emma R L C Vardy, Ronald C. Petersen, Harald Hampel, S. Nicolhaus, Lenore J. Launer, Michelle K. Lupton, Eckart Rüther, A. David Smith, David C. Rubinsztein, Rebecca Sims, Gill Livingston, Diana Zelenika, Simon Mead, Martin N. Rossor, Hilkka Soininen, Christine Van Broeckhoven, Kristel Sleegers, Thorlakur Jonsson, M. Arfan Ikram, Helen Beaumont, Michael Conlon O'Donovan, Federico Licastro, Sudha Seshadri, Alexander Richards, Nick C. Fox, Markus M. Nöthen, Claudine Berr, T. Feulner, Benedetta Nacmias, Carlos Cruchaga, Peter Passmore, Oscar L. Lopez, Julie Williams, Matthias Riemenschneider, Florence Pasquier, John Gallacher, Didier Hannequin, Sigrid Botne Sando, Jens Wiltfang, Charlene Thomas, Gabriele Siciliano, Maria Barcikowska, Mikko Hiltunen, Carol Brayne, Dobril Ivanov, Anita L. DeStefano, Bernadette McGuinness, Norman Klopp, Gordon K. Wilcock, Aoibhinn Lynch, Wolfgang Maier, Peter Holmans, H.-Erich Wichmann, Giorgio Annoni, Beatrice Arosio, Alison Goate, Sigurbjorn Bjornsson, Karl-Heinz Jöckel, Dan Rujescu, Hugh Gurling, Nigel M. Hooper, Clive Holmes, Andrew McQuillin, Patricia Friedrich, John Powell, Rhian Gwilliam, R. Heun, Jacques Epelbaum, Isabella Heuser, Magda Tsolaki, Dennis W. Dickson, Alberto Pilotto, Stephen Todd, Dominique Campion, Michael Krawczak, Jan O. Aasly, Olivier Hanon, Patrick G. Kehoe, Johannes Kornhuber, Marc Delepine, Peter Paul De Deyn, Britta Schürmann, Brian A. Lawlor, Christophe Tzourio, Richard Abraham, Petra Nowotny, Jean-François Dartigues, Heike Kölsch, Michelangelo Mancuso, Marian L. Hamshere, Zbigniew K. Wszolek, Paola Piccardi, Paolo Bosco, Jean-Charles Lambert, Denise Harold, Frank Jessen, Palmi V. Jonsson, Paola Bossù, Paul Hollingworth, Jon Snaedal, Michael Gill, Onofre Combarros, David M. A. Mann, John C. Morris, Annette L. Fitzpatrick, Christopher Shaw, Alexis Brice, Philippe Amouyel, Elio Scarpini, Lesley Jones, Sebastiaan Engelborghs, Daniela Galimberti, Vincenzo Solfrizzi, V. Shane Pankratz, John Collinge, María J. Bullido, Kristelle Brown, Nicholas Bass, Andrew B. Singleton, Jaspreet Singh Pahwa, Kari Stefansson, Lutz Frölich, Steven G. Younkin, Ignacio Mateo, Annick Alpérovitch, Benjamin Genier-Boley, Ina Giegling, Caterina Riehle, Kimberley Dowzell, Mark Lathrop, Hreinn Stefansson, Sandro Sorbi, Rita Guerreiro, Thomas W. Mühleisen, Karolien Bettens, Michael Hüll, Martin Dichgans, Petroula Proitsi, Panagiotis Deloukas, Valentina Moskvina, Cornelia M. van Duijn, Donald Warden, Victoria Alvarez, Eliecer Coto, Kevin Morgan, Susanne Moebus, Ammar Al-Chalabi, Elisa Porcellini, Stefan Wagenpfeil, Hendrik van den Bussche, John S. K. Kauwe, Stacy Steinberg, David Craig, Nicola Jones, Manuel Mayhaus, Davide Seripa, Neurology, NCA - Neurodegeneration, HOLLINGWORTH P, HAROLD D, SIMS R, GERRISH A, LAMBERT JC, CARRASQUILLO MM, ABRAHAM R, HAMSHERE ML, PAHWA JS, MOSKVINA V, DOWZELL K, JONES N, STRETTON A, THOMAS C, RICHARDS A, IVANOV D, WIDDOWSON C, CHAPMAN J, LOVESTONE S, POWELL J, PROITSI P, LUPTON MK, BRAYNE C, RUBINSZTEIN DC, GILL M, LAWLOR B, LYNCH A, BROWN KS, PASSMORE PA, CRAIG D, MCGUINNESS B, TODD S, HOLMES C, MANN D, SMITH AD, BEAUMONT H, WARDEN D, WILCOCK G, LOVE S, KEHOE PG, HOOPER NM, VARDY ER, HARDY J, MEAD S, FOX NC, ROSSOR M, COLLINGE J, MAIER W, JESSEN F, RÜTHER E, SCHÜRMANN B, HEUN R, KÖLSCH H, VAN DEN BUSSCHE H, HEUSER I, KORNHUBER J, WILTFANG J, DICHGANS M, FRÖLICH L, HAMPEL H, GALLACHER J, HÜLL M, RUJESCU D, GIEGLING I, GOATE AM, KAUWE JS, CRUCHAGA C, NOWOTNY P, MORRIS JC, MAYO K, SLEEGERS K, BETTENS K, ENGELBORGHS S, DE DEYN PP, VAN BROECKHOVEN C, LIVINGSTON G, BASS NJ, GURLING H, MCQUILLIN A, GWILLIAM R, DELOUKAS P, AL-CHALABI A, SHAW CE, TSOLAKI M, SINGLETON AB, GUERREIRO R, MÜHLEISEN TW, NÖTHEN MM, MOEBUS S, JÖCKEL KH, KLOPP N, WICHMANN HE, PANKRATZ VS, SANDO SB, AASLY JO, BARCIKOWSKA M, WSZOLEK ZK, DICKSON DW, GRAFF-RADFORD NR, PETERSEN RC, ALZHEIMER'S DISEASE NEUROIMAGING INITIATIVE, VAN DUIJN CM, BRETELER MM, IKRAM MA, DESTEFANO AL, FITZPATRICK AL, LOPEZ O, LAUNER LJ, SESHADRI S, CHARGE CONSORTIUM, BERR C, CAMPION D, EPELBAUM J, DARTIGUES JF, TZOURIO C, ALPÉROVITCH A, LATHROP M, EADI1 CONSORTIUM, FEULNER TM, FRIEDRICH P, RIEHLE C, KRAWCZAK M, SCHREIBER S, MAYHAUS M, NICOLHAUS S, WAGENPFEIL S, STEINBERG S, STEFANSSON H, STEFANSSON K, SNAEDAL J, BJÖRNSSON S, JONSSON PV, CHOURAKI V, GENIER-BOLEY B, HILTUNEN M, SOININEN H, COMBARROS O, ZELENIKA D, DELEPINE M, BULLIDO MJ, PASQUIER F, MATEO I, FRANK-GARCIA A, PORCELLINI E, HANON O, COTO E, ALVAREZ V, BOSCO P, SICILIANO G, MANCUSO M, PANZA F, SOLFRIZZI V, NACMIAS B, SORBI S, BOSSÙ P, PICCARDI P, AROSIO B, ANNONI G, SERIPA D, PILOTTO A, SCARPINI E, GALIMBERTI D, BRICE A, HANNEQUIN D, LICASTRO F, JONES L, HOLMANS PA, JONSSON T, RIEMENSCHNEIDER M, MORGAN K, YOUNKIN SG, OWEN MJ, O'DONOVAN M, AMOUYEL P, WILLIAMS J, Epidemiology, Radiology & Nuclear Medicine, Clinical sciences, Pathologic Biochemistry and Physiology, Hollingworth, P, Harold, D, Sims, R, Gerrish, A, Lambert, J, Carrasquillo, M, Abraham, R, Hamshere, M, Pahwa, J, Moskvina, V, Dowzell, K, Jones, N, Stretton, A, Thomas, C, Richards, A, Ivanov, D, Widdowson, C, Chapman, J, Lovestone, S, Powell, J, Proitsi, P, Lupton, M, Brayne, C, Rubinsztein, D, Gill, M, Lawlor, B, Lynch, A, Brown, K, Passmore, P, Craig, D, Mcguinness, B, Todd, S, Holmes, C, Mann, D, Smith, A, Beaumont, H, Warden, D, Wilcock, G, Love, S, Kehoe, P, Hooper, N, Vardy, E, Hardy, J, Mead, S, Fox, N, Rossor, M, Collinge, J, Maier, W, Jessen, F, Rüther, E, Schürmann, B, Heun, R, Kölsch, H, van den Bussche, H, Heuser, I, Kornhuber, J, Wiltfang, J, Dichgans, M, Frölich, L, Hampel, H, Gallacher, J, Hüll, M, Rujescu, D, Giegling, I, Goate, A, Kauwe, J, Cruchaga, C, Nowotny, P, Morris, J, Mayo, K, Sleegers, K, Bettens, K, Engelborghs, S, De Deyn, P, Van Broeckhoven, C, Livingston, G, Bass, N, Gurling, H, Mcquillin, A, Gwilliam, R, Deloukas, P, Al Chalabi, A, Shaw, C, Tsolaki, M, Singleton, A, Guerreiro, R, Mühleisen, T, Nöthen, M, Moebus, S, Jöckel, K, Klopp, N, Wichmann, H, Pankratz, V, Sando, S, Aasly, J, Barcikowska, M, Wszolek, Z, Dickson, D, Graff Radford, N, Petersen, R, van Duijn, C, Breteler, M, Ikram, M, Destefano, A, Fitzpatrick, A, Lopez, O, Launer, L, Seshadri, S, Berr, C, Campion, D, Epelbaum, J, Dartigues, J, Tzourio, C, Alpérovitch, A, Lathrop, M, Feulner, T, Friedrich, P, Riehle, C, Krawczak, M, Schreiber, S, Mayhaus, M, Nicolhaus, S, Wagenpfeil, S, Steinberg, S, Stefansson, H, Stefansson, K, Snædal, J, Björnsson, S, Jonsson, P, Chouraki, V, Genier Boley, B, Hiltunen, M, Soininen, H, Combarros, O, Zelenika, D, Delepine, M, Bullido, M, Pasquier, F, Mateo, I, Frank Garcia, A, Porcellini, E, Hanon, O, Coto, E, Alvarez, V, Bosco, P, Siciliano, G, Mancuso, M, Panza, F, Solfrizzi, V, Nacmias, B, Sorbi, S, Bossù, P, Piccardi, P, Arosio, B, Annoni, G, Seripa, D, Pilotto, A, Scarpini, E, Galimberti, D, Brice, A, Hannequin, D, Licastro, F, Jones, L, Holmans, P, Jonsson, T, Riemenschneider, M, Morgan, K, Younkin, S, Owen, M, O'Donovan, M, Amouyel, P, and Williams, J

Subjects
Male, ABCA7 protein, human, ATP-Binding Cassette Transporters/genetics, Sialic Acid Binding Ig-like Lectin 3, CD33, SORL1, Medizin, genetics [Alzheimer Disease], Adaptor Proteins, Signal Transducing/genetics, Disease, PICALM, ABCA7, Disease susceptibility, 0302 clinical medicine, genetics [Adaptor Proteins, Signal Transducing], Databases, Genetic, GWAS, GENE-EXPRESSION, Medicine(all), Aged, 80 and over, Genetics, 0303 health sciences, Alzheimer's disease, genetic predisposition, Receptor, EphA1, ALZHEIMER’S DISEASE, Antigens, CD/genetics, genetics [Receptor, EphA1], genetics [Membrane Proteins], Multigene Family, Female, genetics [Antigens, Differentiation, Myelomonocytic], APOE, Antigens, Differentiation, Myelomonocytic, Single-nucleotide polymorphism, Case-control studies, Cytoskeletal Proteins/genetics, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, CD33 protein, human, Alzheimer Disease, Antigens, CD, ddc:570, Humans, Genetic Predisposition to Disease, Membrane Proteins/genetics, CLUSTERIN, Aged, genetics [Cytoskeletal Proteins], Adaptor Proteins, Signal Transducing, 030304 developmental biology, Alzheimer Disease/genetics, Antigens, Differentiation, Myelomonocytic/genetics, Genetic Variation, Membrane Proteins, CD2-associated protein, genetics [Antigens, CD], Cytoskeletal Proteins, MS4A4E protein, human, Case-Control Studies, Susceptibility locus, biology.protein, ATP-Binding Cassette Transporters, Human medicine, genetics [ATP-Binding Cassette Transporters], aged, 80 and over, Receptor, EphA1/genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ĝ‰Currency sign 1 × 10 -5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10 -17; including ADGC data, meta P = 5.0 × 10 -21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10 -14; including ADGC data, meta P = 1.2 × 10 -16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10 -4; including ADGC data, meta P = 8.6 × 10 -9), CD33 (GERAD+, P = 2.2 × 10 -4; including ADGC data, meta P = 1.6 × 10 -9) and EPHA1 (GERAD+, P = 3.4 × 10 -4; including ADGC data, meta P = 6.0 × 10 -10). © 2011 Nature America, Inc. All rights reserved.

Published
2011

50. Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

Author

Anne Boland, Giorgio Annoni, Elisa Porcellini, Gloria Tognoni, Giovanni Ravaglia, Mark Lathrop, Ignacio Mateo, Paola Bossù, Diana Zelenika, Nathalie Fievet, Marc Delepine, Mikko Hiltunen, Ana Frank-García, Hilkka Soininen, Paola Forti, Gianfranco Spalletta, Federico Licastro, Daniela Galimberti, Paola Piccardi, Maria Del Zompo, Seppo Helisalmi, Michelangelo Mancuso, Vincenzo Solfrizzi, Francesco Panza, Davide Seripa, Philippe Amouyel, María J. Bullido, Paolo Bosco, Gabriele Siciliano, Alberto Pilotto, Vincent Chouraki, Beatrice Arosio, Fernando Valdivieso, Jean-Charles Lambert, Elio Scarpini, Victoria Alvarez, Onofre Combarros, Sandro Sorbi, Benedetta Nacmias, Raffaele Ferri, Eliecer Coto, Lambert, J, Zelenika, D, Hiltunen, M, Chouraki, V, Combarros, O, Bullido, M, Tognoni, G, Fiévet, N, Boland, A, Arosio, B, Coto, E, Zompo, M, Mateo, I, Frank Garcia, A, Helisalmi, S, Porcellini, E, Pilotto, A, Forti, P, Ferri, R, Delepine, M, Scarpini, E, Siciliano, G, Solfrizzi, V, Sorbi, S, Spalletta, G, Ravaglia, G, Valdivieso, F, Alvarez, V, Bosco, P, Mancuso, M, Panza, F, Nacmias, B, Bossù, P, Piccardi, P, Annoni, G, Seripa, D, Galimberti, D, Licastro, F, Lathrop, M, Soininen, H, Amouyel, P, Lambert JC, Zelenika D, Hiltunen M, Chouraki V, Combarros O, Bullido MJ, Tognoni G, Fiévet N, Boland A, Arosio B, Coto E, Zompo MD, Mateo I, Frank-Garcia A, Helisalmi S, Porcellini E, Pilotto A, Forti P, Ferri R, Delepine M, Scarpini E, Siciliano G, Solfrizzi V, Sorbi S, Spalletta G, Ravaglia G, Valdivieso F, Alvarez V, Bosco P, Mancuso M, Panza F, Nacmias B, Bossù P, Piccardi P, Annoni G, Seripa D, Galimberti D, Licastro F, Lathrop M, Soininen H, Amouyel P, and Universidad de Cantabria

Subjects
Apolipoprotein E, Aging, BIN1, Genotype, Disease, Biology, GWA, Polymorphism, Single Nucleotide, White People, PICALM, Polymorphism (computer science), Alzheimer Disease, Humans, Genetic Predisposition to Disease, Finland, Genetic Association Studies, Genetic association, Adaptor Proteins, Signal Transducing, Genetics, ALZHEIMER’S DISEASE, General Neuroscience, Tumor Suppressor Proteins, Nuclear Proteins, Odds ratio, POLYMORPHISM, Confidence interval, Italy, Spain, Monomeric Clathrin Assembly Proteins, Neurology (clinical), BIN1, PICALM, EXOC3L2, APOE, Alzheimer, Risk, GWA, Association, Polymorphism, Geriatrics and Gerontology, APOE, Developmental Biology
Abstract

Recent genome-wide association studies have identified 5 loci (BIM, CLU, CR1, EXOC3L2, and PICALM) as genetic determinants of Alzheimer's disease (AD). We attempted to confirm the association between these genes and the AD risk in 3 contrasting European populations (from Finland, Italy, and Spain). Because CLU and CRI had already been analyzed in these populations, we restricted our investigation to BIN1, EXO2CL3, and PICALM. In a total of 2816 AD cases and 2706 controls, we unambiguously replicated the association of rs744373 (for BIN1) and rs541458 (for PICALM) polymorphisms with the AD risk (odds ratio [OR] = 1.26, 95% confidence interval [Cl] [1.15-1.38], p = 2.9 X 10(-7), and OR = 0.80, 95% CI [0.74-0.88], p = 4.6 X 10(-7), respectively). In a meta-analysis, rs597668 (EXOC3L2) was also associated with the AD risk, albeit to a lesser extent (OR = 1.19, 95% Cl [1.06-1.32], p = 2.0 X 10(-3)). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN! and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation. (C) 2011 Elsevier Inc. All rights reserved.

Published
2011

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