150 results on '"Marioni, R."'
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2. New insights into the genetic etiology of Alzheimer's disease and related dementias
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Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., Holmans, P. A., Boland, A., Damotte, V., van der Lee, S. J., Costa, M. R., Kuulasmaa, T., Yang, Q., de Rojas, I., Bis, J. C., Yaqub, A., Prokic, I., Chapuis, J., Ahmad, S., Giedraitis, V., Aarsland, D., Garcia-Gonzalez, P., Abdelnour, C., Alarcón-Martín, E., Alcolea, D., Alegret, M., Alvarez, I., Álvarez, V., Armstrong, N. J., Tsolaki, A., Antúnez, C., Appollonio, I., Arcaro, M., Archetti, S., Pastor, A. A., Arosio, B., Athanasiu, L., Bailly, H., Banaj, N., Baquero, M., Barral, S., Beiser, A., Pastor, A. B., Below, J. E., Benchek, P., Benussi, L., Berr, C., Besse, C., Bessi, V., Binetti, G., Bizarro, A., Blesa, R., Boada, M., Boerwinkle, E., Borroni, B., Boschi, S., Bossù, P., Bråthen, G., Bressler, J., Bresner, C., Brodaty, H., Brookes, K. J., Brusco, L. I., Buiza-Rueda, D., Bûrger, K., Burholt, V., Bush, W. S., Calero, M., Cantwell, L. B., Chene, G., Chung, J., Cuccaro, M. L., Carracedo, Á., Cecchetti, R., Cervera-Carles, L., Charbonnier, C., Chen, H. -H., Chillotti, C., Ciccone, S., Claassen, J. A. H. R., Clark, C., Conti, E., Corma-Gómez, A., Costantini, E., Custodero, C., Daian, D., Dalmasso, M. C., Daniele, A., Dardiotis, E., Dartigues, J. -F., de Deyn, P. P., de Paiva Lopes, K., de Witte, L. D., Debette, S., Deckert, J., del Ser, T., Denning, N., Destefano, A., Dichgans, M., Diehl-Schmid, J., Diez-Fairen, M., Rossi, P. D., Djurovic, S., Duron, E., Düzel, E., Dufouil, C., Eiriksdottir, G., Engelborghs, S., Escott-Price, V., Espinosa, A., Ewers, M., Faber, K. M., Fabrizio, T., Nielsen, S. F., Fardo, D. W., Farotti, L., Fenoglio, C., Fernández-Fuertes, M., Ferrari, R., Ferreira, C. B., Ferri, E., Fin, B., Fischer, P., Fladby, T., Fließbach, K., Fongang, B., Fornage, M., Fortea, J., Foroud, T. M., Fostinelli, S., Fox, N. C., Franco-Macías, E., Bullido, M. J., Frank-García, A., Froelich, L., Fulton-Howard, B., Galimberti, D., García-Alberca, J. M., García-González, P., Garcia-Madrona, S., Garcia-Ribas, G., Ghidoni, R., Giegling, I., Giorgio, G., Goate, A. M., Goldhardt, O., Gomez-Fonseca, D., González-Pérez, A., Graff, C., Grande, G., Green, E., Grimmer, T., Grünblatt, E., Grunin, M., Gudnason, V., Guetta-Baranes, T., Haapasalo, A., Hadjigeorgiou, G., Haines, J. L., Hamilton-Nelson, K. L., Hampel, H., Hanon, O., Hardy, J., Hartmann, A. M., Hausner, L., Harwood, J., Heilmann-Heimbach, S., Helisalmi, S., Heneka, M. T., Hernández, I., Herrmann, M. J., Hoffmann, P., Holmes, C., Holstege, H., Vilas, R. H., Hulsman, M., Humphrey, J., Biessels, G. J., Jian, X., Johansson, C., Jun, G. R., Kastumata, Y., Kauwe, J., Kehoe, P. G., Kilander, L., Ståhlbom, A. K., Kivipelto, M., Koivisto, A., Kornhuber, J., Kosmidis, M. H., Kukull, W. A., Kuksa, P. P., Kunkle, B. W., Kuzma, A. B., Lage, C., Laukka, E. J., Launer, L., Lauria, A., Lee, C. -Y., Lehtisalo, J., Lerch, O., Lleó, A., Longstreth, W., Lopez, O., de Munain, A. L., Love, S., Löwemark, M., Luckcuck, L., Lunetta, K. L., Ma, Y., Macías, J., Macleod, C. A., Maier, W., Mangialasche, F., Spallazzi, M., Marquié, M., Marshall, R., Martin, E. R., Montes, A. M., Rodríguez, C. M., Masullo, C., Mayeux, R., Mead, S., Mecocci, P., Medina, M., Meggy, A., Mehrabian, S., Mendoza, S., Menéndez-González, M., Mir, P., Moebus, S., Mol, M., Molina-Porcel, L., Montrreal, L., Morelli, L., Moreno, F., Morgan, K., Mosley, T., Nöthen, M. M., Muchnik, C., Mukherjee, S., Nacmias, B., Ngandu, T., Nicolas, G., Nordestgaard, B. G., Olaso, R., Orellana, A., Orsini, M., Ortega, G., Padovani, A., Paolo, C., Papenberg, G., Parnetti, L., Pasquier, F., Pastor, P., Peloso, G., Pérez-Cordón, A., Pérez-Tur, J., Pericard, P., Peters, O., Pijnenburg, Y. A. L., Pineda, J. A., Piñol-Ripoll, G., Pisanu, C., Polak, T., Popp, J., Posthuma, D., Priller, J., Puerta, R., Quenez, O., Quintela, I., Thomassen, J. Q., Rábano, A., Rainero, I., Rajabli, F., Ramakers, I., Real, L. M., Reinders, M. J. T., Reitz, C., Reyes-Dumeyer, D., Ridge, P., Riedel-Heller, S., Riederer, P., Roberto, N., Rodriguez-Rodriguez, E., Rongve, A., Allende, I. R., Rosende-Roca, M., Royo, J. L., Rubino, E., Rujescu, D., Sáez, M. E., Sakka, P., Saltvedt, I., Sanabria, Á., Sánchez-Arjona, M. B., Sanchez-Garcia, F., Juan, P. S., Sánchez-Valle, R., Sando, S. B., Sarnowski, C., Satizabal, C. L., Scamosci, M., Scarmeas, N., Scarpini, E., Scheltens, P., Scherbaum, N., Scherer, M., Schmid, M., Schneider, A., Schott, J. M., Selbæk, G., Seripa, D., Serrano, M., Sha, J., Shadrin, A. A., Skrobot, O., Slifer, S., Snijders, G. J. L., Soininen, H., Solfrizzi, V., Solomon, A., Song, Y. E., Sorbi, S., Sotolongo-Grau, O., Spalletta, G., Spottke, A., Squassina, A., Stordal, E., Tartan, J. P., Tárraga, L., Tesí, N., Thalamuthu, A., Thomas, T., Tosto, G., Traykov, L., Tremolizzo, L., Tybjærg-Hansen, A., Uitterlinden, A., Ullgren, A., Ulstein, I., Valero, S., Valladares, O., Broeckhoven, C. V., Vance, J., Vardarajan, B. N., van der Lugt, A., Dongen, J. V., van Rooij, J., van Swieten, J., Vandenberghe, R., Verhey, F., Vidal, J. -S., Vogelgsang, J., Vyhnalek, M., Wagner, M., Wallon, D., Wang, L. -S., Wang, R., Weinhold, L., Wiltfang, J., Windle, G., Woods, B., Yannakoulia, M., Zare, H., Zhao, Y., Zhang, X., Zhu, C., Zulaica, M., Laczo, J., Matoska, V., Serpente, M., Assogna, F., Piras, F., Ciullo, V., Shofany, J., Ferrarese, C., Andreoni, S., Sala, G., Zoia, C. P., Zompo, M. D., Benussi, A., Bastiani, P., Takalo, M., Natunen, T., Laatikainen, T., Tuomilehto, J., Antikainen, R., Strandberg, T., Lindström, J., Peltonen, M., Abraham, R., Al-Chalabi, A., Bass, N. J., Brayne, C., Brown, K. S., Collinge, J., Craig, D., Deloukas, P., Fox, N., Gerrish, A., Gill, M., Gwilliam, R., Harold, D., Hollingworth, P., Johnston, J. A., Jones, L., Lawlor, B., Livingston, G., Lovestone, S., Lupton, M., Lynch, A., Mann, D., Mcguinness, B., Mcquillin, A., O’Donovan, M. C., Owen, M. J., Passmore, P., Powell, J. F., Proitsi, P., Rossor, M., Shaw, C. E., Smith, A. D., Gurling, H., Todd, S., Mummery, C., Ryan, N., Lacidogna, G., Adarmes-Gómez, A., Mauleón, A., Pancho, A., Gailhajenet, A., Lafuente, A., Macias-García, D., Martín, E., Pelejà, E., Carrillo, F., Merlín, I. S., Garrote-Espina, L., Vargas, L., Carrion-Claro, M., Marín, M., Labrador, M., Buendia, M., Alonso, M. 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E., Mars, N., Pelkonen, M., Kauppi, P., Kankaanranta, H., Harju, T., Close, D., Greenberg, S., Chen, H., Betts, J., Ghosh, S., Salomaa, V., Niiranen, T., Juonala, M., Metsärinne, K., Kähönen, M., Junttila, J., Laakso, M., Pihlajamäki, J., Sinisalo, J., Taskinen, M. -R., Tuomi, T., Challis, B., Peterson, A., Chu, A., Parkkinen, J., Muslin, A., Joensuu, H., Meretoja, T., Aaltonen, L., Mattson, J., Auranen, A., Karihtala, P., Kauppila, S., Auvinen, P., Elenius, K., Popovic, R., Schutzman, J., Loboda, A., Chhibber, A., Lehtonen, H., Mcdonough, S., Crohns, M., Kulkarni, D., Kaarniranta, K., Turunen, J. A., Ollila, T., Seitsonen, S., Uusitalo, H., Aaltonen, V., Uusitalo-Järvinen, H., Luodonpää, M., Hautala, N., Loomis, S., Strauss, E., Podgornaia, A., Hoffman, J., Tasanen, K., Huilaja, L., Hannula-Jouppi, K., Salmi, T., Peltonen, S., Koulu, L., Harvima, I., Wu, Y., Choy, D., Pussinen, P., Salminen, A., Salo, T., Rice, D., Nieminen, P., Palotie, U., Siponen, M., Suominen, L., Mäntylä, P., Gursoy, U., Anttonen, V., Sipilä, K., Davis, J. W., Quarless, D., Petrovski, S., Wigmore, E., Chen, C. -Y., Bronson, P., Tsai, E., Huang, Y., Maranville, J., Shaikho, E., Mohammed, E., Wadhawan, S., Kvikstad, E., Caliskan, M., Chang, D., Bhangale, T., Pendergrass, S., Holzinger, E., Chen, X., Hedman, Å., King, K. S., Wang, C., Xu, E., Auge, F., Chatelain, C., Rajpal, D., Liu, D., Xia, T. -H., Brauer, M., Kurki, M., Karjalainen, J., Havulinna, A., Jalanko, A., Palta, P., della Briotta Parolo, P., Zhou, W., Lemmelä, S., Rivas, M., Harju, J., Lehisto, A., Ganna, A., Llorens, V., Laivuori, H., Rüeger, S., Niemi, M. E., Tukiainen, T., Reeve, M. P., Heyne, H., Palin, K., Garcia-Tabuenca, J., Siirtola, H., Kiiskinen, T., Lee, J., Tsuo, K., Elliott, A., Kristiansson, K., Hyvärinen, K., Ritari, J., Koskinen, M., Pylkäs, K., Kalaoja, M., Karjalainen, M., Mantere, T., Kangasniemi, E., Heikkinen, S., Laakkonen, E., Sipeky, C., Heron, S., Karlsson, A., Jambulingam, D., Rathinakannan, V. S., Kajanne, R., Aavikko, M., Jiménez, M. G., della Briotta Parola, P., Kanai, M., Kaunisto, M., Kilpeläinen, E., Sipilä, T. 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L., Litkowski, E., Li, S., Liu, X., Loitfelder, M., Manning, A., Maillard, P., Marioni, R., Mazoyer, B., van Lent, D. M., Mei, H., Mishra, A., Nyquist, P., O’Connell, J., Paus, T., Pausova, Z., Raikkonen-Talvitie, K., Riaz, M., Rich, S., Rotter, J., Romero, J., Roshchupkin, G., Saba, Y., Sargurupremraj, M., Schmidt, H., Schmidt, R., Shulman, J. M., Smith, J., Sekhar, H., Rajula, R., Shin, J., Simino, J., Sliz, E., Teumer, A., Thomas, A., Tin, A., Tucker-Drob, E., Vojinovic, D., Wang, Y., Weinstein, G., Williams, D., Wittfeld, K., Yanek, L., Yang, Y., Farrer, L. A., Psaty, B. M., Ghanbari, M., Raj, T., Sachdev, P., Mather, K., Jessen, F., Ikram, M. A., de Mendonça, A., Hort, J., Tsolaki, M., Pericak-Vance, M. A., Amouyel, P., Williams, J., Frikke-Schmidt, R., Clarimon, J., Deleuze, J. -F., Rossi, G., Seshadri, S., Andreassen, O. A., Ingelsson, M., Hiltunen, M., Sleegers, K., Schellenberg, G. D., van Duijn, C. M., Sims, R., van der Flier, W. 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Uitterlinden, A, Ullgren, A, Ulstein, I, Valero, S, Valladares, O, Broeckhoven, C, Vance, J, Vardarajan, B, van der Lugt, A, Dongen, J, van Rooij, J, van Swieten, J, Vandenberghe, R, Verhey, F, Vidal, J, Vogelgsang, J, Vyhnalek, M, Wagner, M, Wallon, D, Wang, L, Wang, R, Weinhold, L, Wiltfang, J, Windle, G, Woods, B, Yannakoulia, M, Zare, H, Zhao, Y, Zhang, X, Zhu, C, Zulaica, M, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Farrer, L, Psaty, B, Ghanbari, M, Raj, T, Sachdev, P, Mather, K, Jessen, F, Ikram, M, de Mendonça, A, Hort, J, Tsolaki, M, Pericak-Vance, M, Amouyel, P, Williams, J, Frikke-Schmidt, R, Clarimon, J, Deleuze, J, Rossi, G, Seshadri, S, Andreassen, O, Ingelsson, M, Hiltunen, M, Sleegers, K, Schellenberg, G, van Duijn, C, Sims, R, van der Flier, W, Ruiz, A, Ramirez, A, Lambert, J, VU University medical center, Amsterdam Neuroscience - Neurodegeneration, Neurology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Compulsivity, 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Spec Psychiatrie (9), UAM. Departamento de Biología Molecular, University of Helsinki, Department of Neurosciences, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Neurocenter, Neurologian yksikkö, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (France), European Commission, LabEx DISTALZ, Pérez-Tur, Jordi, University Children’s Hospital Basel (Suiza), INSERM (Francia), Lille Métropole Communauté Urbaine, Government of France (Francia), EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Holmans, Peter A. [0000-0003-0870-9412], van der Lee, Sven J. [0000-0003-1606-8643], Costa, Marcos R. [0000-0002-4928-2163], Bis, Joshua C. [0000-0002-3409-1110], Brookes, Keeley J. [0000-0003-2427-2513], Bush, William S. [0000-0002-9729-6519], de Witte, Lot D. [0000-0002-7235-9958], del Ser, Teodoro [0000-0001-9806-7083], Fox, Nick C. [0000-0002-6660-657X], Bullido, María J. [0000-0002-6477-1117], Goate, Alison M. [0000-0002-0576-2472], Herrmann, Martin J. [0000-0001-9970-2122], Jun, Gyungah R. [0000-0002-3230-8697], Kehoe, Patrick G. [0000-0002-7542-1139], Kosmidis, Mary H. [0000-0001-8790-1220], Lunetta, Kathryn L. [0000-0002-9268-810X], MacLeod, Catherine A. [0000-0002-9314-7380], Nöthen, Markus M. [0000-0002-8770-2464], Nordestgaard, Børge G. [0000-0002-1954-7220], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis M. [0000-0003-4932-7429], Reinders, Marcel J. T. [0000-0002-1148-1562], Satizabal, Claudia L. [0000-0002-1115-4430], Schott, Jonathan M. [0000-0003-2059-024X], Shadrin, Alexey A. [0000-0002-7467-250X], Farrer, Lindsay A. [0000-0001-5533-4225], Psaty, Bruce M. [0000-0002-7278-2190], Ikram, M. Arfan [0000-0003-0372-8585], Pericak-Vance, Margaret A. [0000-0001-7283-8804], Andreassen, Ole A. [0000-0002-4461-3568], van Duijn, Cornelia M. [0000-0002-2374-9204], van der Flier, Wiesje M. [0000-0001-8766-6224], and Molecular Neuroscience and Ageing Research (MOLAR)
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tau Proteins/genetics ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Neurologi ,MED/03 - GENETICA MEDICA ,45/43 ,Medizin ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,genetics [Alzheimer Disease] ,Genome-Wide Association Study ,Humans ,tau Proteins ,Alzheimer Disease ,Cognitive Dysfunction ,VARIANTS ,pathology [Alzheimer Disease] ,Tau Proteins ,Settore BIO/13 - Biologia Applicata ,Cognitive Dysfunction/psychology ,692/699/375/365/1283 ,IMPUTATION ,article ,1184 Genetics, developmental biology, physiology ,Biología y Biomedicina / Biología ,AMYLOID-BETA ,Settore MED/26 - NEUROLOGIA ,Neurology ,psychology [Cognitive Dysfunction] ,Medical Genetics ,Human ,Neuroscience(all) ,631/208/205/2138 ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,ddc:570 ,Genetics ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,Medicinsk genetik ,MED/26 - NEUROLOGIA ,Alzheimer Disease/genetics ,neurology ,tau Protein ,NECROSIS-FACTOR-ALPHA ,RISK LOCI ,genetics [tau Proteins] ,PREDICTION MODELS ,Human medicine ,GENERATION ,RESPONSES - Abstract
25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not
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- 2022
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3. 275 Identification of DNA methylation signatures associated with atopic eczema
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Sampson, J., primary, Scotland, G., additional, McCartney, D., additional, Marioni, R., additional, and Brown, S.J., additional
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- 2022
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4. Anticholinergic burden in middle and older age is associated with lower cognitive function, but not with brain atrophy
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Mur, J., primary, Marioni, R. E., additional, Russ, T. C., additional, Muniz-Terrera, G., additional, and Cox, S. R., additional
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- 2022
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5. An epigenome-wide association study meta-analysis of educational attainment
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Linnér, R Karlsson, Marioni, R E, Rietveld, C A, Simpkin, A J, Davies, N M, Watanabe, K, Armstrong, N J, Auro, K, Baumbach, C, Bonder, M J, Buchwald, J, Fiorito, G, Ismail, K, Iurato, S, Joensuu, A, Karell, P, Kasela, S, Lahti, J, McRae, A F, Mandaviya, P R, Seppälä, I, Wang, Y, Baglietto, L, Binder, E B, Harris, S E, Hodge, A M, Horvath, S, Hurme, M, Johannesson, M, Latvala, A, Mather, K A, Medland, S E, Metspalu, A, Milani, L, Milne, R L, Pattie, A, Pedersen, N L, Peters, A, Polidoro, S, Räikkönen, K, Severi, G, Starr, J M, Stolk, L, Waldenberger, M, Consortium, B IOS, Eriksson, J G, Esko, T, Franke, L, Gieger, C, Giles, G G, Hägg, S, Jousilahti, P, Kaprio, J, Kähönen, M, Lehtimäki, T, Martin, N G, van Meurs, J BC, Ollikainen, M, Perola, M, Posthuma, D, Raitakari, O T, Sachdev, P S, Taskesen, E, Uitterlinden, A G, Vineis, P, Wijmenga, C, Wright, M J, Relton, C, Smith, G Davey, Deary, I J, Koellinger, P D, and Benjamin, D J
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- 2017
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6. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
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Davies, G, Armstrong, N, Bis, J C, Bressler, J, Chouraki, V, Giddaluru, S, Hofer, E, Ibrahim-Verbaas, C A, Kirin, M, Lahti, J, van der Lee, S J, Le Hellard, S, Liu, T, Marioni, R E, Oldmeadow, C, Postmus, I, Smith, A V, Smith, J A, Thalamuthu, A, Thomson, R, Vitart, V, Wang, J, Yu, L, Zgaga, L, Zhao, W, Boxall, R, Harris, S E, Hill, W D, Liewald, D C, Luciano, M, Adams, H, Ames, D, Amin, N, Amouyel, P, Assareh, A A, Au, R, Becker, J T, Beiser, A, Berr, C, Bertram, L, Boerwinkle, E, Buckley, B M, Campbell, H, Corley, J, De Jager, P L, Dufouil, C, Eriksson, J G, Espeseth, T, Faul, J D, Ford, I, Scotland, Generation, Gottesman, R F, Griswold, M E, Gudnason, V, Harris, T B, Heiss, G, Hofman, A, Holliday, E G, Huffman, J, Kardia, S L R, Kochan, N, Knopman, D S, Kwok, J B, Lambert, J-C, Lee, T, Li, G, Li, S-C, Loitfelder, M, Lopez, O L, Lundervold, A J, Lundqvist, A, Mather, K A, Mirza, S S, Nyberg, L, Oostra, B A, Palotie, A, Papenberg, G, Pattie, A, Petrovic, K, Polasek, O, Psaty, B M, Redmond, P, Reppermund, S, Rotter, J I, Schmidt, H, Schuur, M, Schofield, P W, Scott, R J, Steen, V M, Stott, D J, van Swieten, J C, Taylor, K D, Trollor, J, Trompet, S, Uitterlinden, A G, Weinstein, G, Widen, E, Windham, B G, Jukema, J W, Wright, A F, Wright, M J, Yang, Q, Amieva, H, Attia, J R, Bennett, D A, Brodaty, H, de Craen, A J M, Hayward, C, Ikram, M A, Lindenberger, U, Nilsson, L-G, Porteous, D J, Räikkönen, K, Reinvang, I, Rudan, I, Sachdev, P S, Schmidt, R, Schofield, P R, Srikanth, V, Starr, J M, Turner, S T, Weir, D R, Wilson, J F, van Duijn, C, Launer, L, Fitzpatrick, A L, Seshadri, S, Mosley, Jr, T H, and Deary, I J
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- 2015
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7. DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases
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Wielscher, M. (Matthias), Mandaviya, P. R. (Pooja R.), Kuehnel, B. (Brigitte), Joehanes, R. (Roby), Mustafa, R. (Rima), Robinson, O. (Oliver), Zhang, Y. (Yan), Bodinier, B. (Barbara), Walton, E. (Esther), Mishra, P. P. (Pashupati P.), Schlosser, P. (Pascal), Wilson, R. (Rory), Tsai, P.-C. (Pei-Chien), Palaniswamy, S. (Saranya), Marioni, R. E. (Riccardo E.), Fiorito, G. (Giovanni), Cugliari, G. (Giovanni), Karhunen, V. (Ville), Ghanbari, M. (Mohsen), Psaty, B. M. (Bruce M.), Loh, M. (Marie), Bis, J. C. (Joshua C.), Lehne, B. (Benjamin), Sotoodehnia, N. (Nona), Deary, I. J. (Ian J.), Chadeau-Hyam, M. (Marc), Brody, J. A. (Jennifer A.), Cardona, A. (Alexia), Selvin, E. (Elizabeth), Smith, A. K. (Alicia K.), Miller, A. H. (Andrew H.), Torres, M. A. (Mylin A.), Marouli, E. (Eirini), Gao, X. (Xin), van Meurs, J. B. (Joyce B. J.), Graf-Schindler, J. (Johanna), Rathmann, W. (Wolfgang), Koenig, W. (Wolfgang), Peters, A. (Annette), Weninger, W. (Wolfgang), Farlik, M. (Matthias), Zhang, T. (Tao), Chen, W. (Wei), Xia, Y. (Yujing), Teumer, A. (Alexander), Nauck, M. (Matthias), Grabe, H. J. (Hans J.), Doerr, M. (Macus), Lehtimaki, T. (Terho), Guan, W. (Weihua), Milani, L. (Lili), Tanaka, T. (Toshiko), Fisher, K. (Krista), Waite, L. L. (Lindsay L.), Kasela, S. (Silva), Vineis, P. (Paolo), Verweij, N. (Niek), van der Harst, P. (Pim), Iacoviello, L. (Licia), Sacerdote, C. (Carlotta), Panico, S. (Salvatore), Krogh, V. (Vittorio), Tumino, R. (Rosario), Tzala, E. (Evangelia), Matullo, G. (Giuseppe), Hurme, M. A. (Mikko A.), Raitakari, O. T. (Olli T.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Kahonen, M. (Mika), Herzig, K.-H. (Karl-Heinz), Li, S. (Shengxu), BIOS consortium, Conneely, K. N. (Karen N.), Kooner, J. S. (Jaspal S.), Kottgen, A. (Anna), Heijmans, B. T. (Bastiaan T.), Deloukas, P. (Panos), Relton, C. (Caroline), Ong, K. K. (Ken K.), Bell, J. T. (Jordana T.), Boerwinkle, E. (Eric), Elliott, P. (Paul), Brenner, H. (Hermann), Beekman, M. (Marian), Levy, D. (Daniel), Waldenberger, M. (Melanie), Chambers, J. C. (John C.), Dehghan, A. (Abbas), Järvelin, M.-R. (Marjo-Riitta), Wielscher, M. (Matthias), Mandaviya, P. R. (Pooja R.), Kuehnel, B. (Brigitte), Joehanes, R. (Roby), Mustafa, R. (Rima), Robinson, O. (Oliver), Zhang, Y. (Yan), Bodinier, B. (Barbara), Walton, E. (Esther), Mishra, P. P. (Pashupati P.), Schlosser, P. (Pascal), Wilson, R. (Rory), Tsai, P.-C. (Pei-Chien), Palaniswamy, S. (Saranya), Marioni, R. E. (Riccardo E.), Fiorito, G. (Giovanni), Cugliari, G. (Giovanni), Karhunen, V. (Ville), Ghanbari, M. (Mohsen), Psaty, B. M. (Bruce M.), Loh, M. (Marie), Bis, J. C. (Joshua C.), Lehne, B. (Benjamin), Sotoodehnia, N. (Nona), Deary, I. J. (Ian J.), Chadeau-Hyam, M. (Marc), Brody, J. A. (Jennifer A.), Cardona, A. (Alexia), Selvin, E. (Elizabeth), Smith, A. K. (Alicia K.), Miller, A. H. (Andrew H.), Torres, M. A. (Mylin A.), Marouli, E. (Eirini), Gao, X. (Xin), van Meurs, J. B. (Joyce B. J.), Graf-Schindler, J. (Johanna), Rathmann, W. (Wolfgang), Koenig, W. (Wolfgang), Peters, A. (Annette), Weninger, W. (Wolfgang), Farlik, M. (Matthias), Zhang, T. (Tao), Chen, W. (Wei), Xia, Y. (Yujing), Teumer, A. (Alexander), Nauck, M. (Matthias), Grabe, H. J. (Hans J.), Doerr, M. (Macus), Lehtimaki, T. (Terho), Guan, W. (Weihua), Milani, L. (Lili), Tanaka, T. (Toshiko), Fisher, K. (Krista), Waite, L. L. (Lindsay L.), Kasela, S. (Silva), Vineis, P. (Paolo), Verweij, N. (Niek), van der Harst, P. (Pim), Iacoviello, L. (Licia), Sacerdote, C. (Carlotta), Panico, S. (Salvatore), Krogh, V. (Vittorio), Tumino, R. (Rosario), Tzala, E. (Evangelia), Matullo, G. (Giuseppe), Hurme, M. A. (Mikko A.), Raitakari, O. T. (Olli T.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Kahonen, M. (Mika), Herzig, K.-H. (Karl-Heinz), Li, S. (Shengxu), BIOS consortium, Conneely, K. N. (Karen N.), Kooner, J. S. (Jaspal S.), Kottgen, A. (Anna), Heijmans, B. T. (Bastiaan T.), Deloukas, P. (Panos), Relton, C. (Caroline), Ong, K. K. (Ken K.), Bell, J. T. (Jordana T.), Boerwinkle, E. (Eric), Elliott, P. (Paul), Brenner, H. (Hermann), Beekman, M. (Marian), Levy, D. (Daniel), Waldenberger, M. (Melanie), Chambers, J. C. (John C.), Dehghan, A. (Abbas), and Järvelin, M.-R. (Marjo-Riitta)
- Abstract
We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.
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- 2022
8. Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations
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Temprano-Sagrera, G, Sitlani, CM, Bone, WP, Martin-Bornez, M, Voight, BF, Morrison, AC, Damrauer, SM, de Vries, PS, Smith, NL, Sabater-Lleal, M, Krupinksi, J, Dehghan, A, Heath, AS, Reiner, AP, Johnson, A, Richmond, A, Peters, A, van Hylckama Vlieg, A, McKnight, B, Psaty, BM, Hayward, C, Ward-Caviness, C, O’Donnell, C, Chasman, D, Strachan, DP, Tregouet, DA, Mook-Kanamori, D, Gill, D, Thibord, F, Asselbergs, FW, Leebeek, FWG, Rosendaal, FR, Davies, G, Homuth, G, Temprano, G, Campbell, H, Taylor, HA, Bressler, J, Huffman, JE, Rotter, JI, Yao, J, Wilson, JF, Bis, JC, Hahn, JM, Desch, KC, Wiggins, KL, Raffield, LM, Bielak, LF, Yanek, LR, Kleber, ME, Mueller, M, Kavousi, M, Mangino, M, Liu, M, Brown, MR, Conomos, MP, Jhun, MA, Chen, MH, de Maat, MPM, Pankratz, N, Peyser, PA, Elliot, P, Wei, P, Wild, PS, Morange, PE, van der Harst, P, Yang, Q, Le, NQ, Marioni, R, Li, R, Cox, SR, Trompet, S, Felix, SB, Völker, U, Tang, W, Koenig, W, Jukema, JW, Guo, X, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, de Andrade, M, Brody, JA, Pattee, JW, Haessler, J, Brumpton, BM, Chasman, DI, Suchon, P, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Temprano-Sagrera, G, Sitlani, CM, Bone, WP, Martin-Bornez, M, Voight, BF, Morrison, AC, Damrauer, SM, de Vries, PS, Smith, NL, Sabater-Lleal, M, Krupinksi, J, Dehghan, A, Heath, AS, Reiner, AP, Johnson, A, Richmond, A, Peters, A, van Hylckama Vlieg, A, McKnight, B, Psaty, BM, Hayward, C, Ward-Caviness, C, O’Donnell, C, Chasman, D, Strachan, DP, Tregouet, DA, Mook-Kanamori, D, Gill, D, Thibord, F, Asselbergs, FW, Leebeek, FWG, Rosendaal, FR, Davies, G, Homuth, G, Temprano, G, Campbell, H, Taylor, HA, Bressler, J, Huffman, JE, Rotter, JI, Yao, J, Wilson, JF, Bis, JC, Hahn, JM, Desch, KC, Wiggins, KL, Raffield, LM, Bielak, LF, Yanek, LR, Kleber, ME, Mueller, M, Kavousi, M, Mangino, M, Liu, M, Brown, MR, Conomos, MP, Jhun, MA, Chen, MH, de Maat, MPM, Pankratz, N, Peyser, PA, Elliot, P, Wei, P, Wild, PS, Morange, PE, van der Harst, P, Yang, Q, Le, NQ, Marioni, R, Li, R, Cox, SR, Trompet, S, Felix, SB, Völker, U, Tang, W, Koenig, W, Jukema, JW, Guo, X, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, de Andrade, M, Brody, JA, Pattee, JW, Haessler, J, Brumpton, BM, Chasman, DI, Suchon, P, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, and Armasu, SM
- Abstract
Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.
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- 2022
9. Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus (vol 13, 1222, 2022)
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Stacey, D, Chen, LY, Stanczyk, PJ, Howson, JMM, Mason, AM, Burgess, S, MacDonald, S, Langdown, J, McKinney, H, Downes, K, Farahi, N, Peters, JE, Basu, S, Pankow, JS, Tang, WH, Pankratz, N, Sabater-Lleal, M, de Vries, PS, Smith, NL, Dehghan, A, Heath, AS, Morrison, AC, Reiner, AP, Johnson, A, Richmond, A, Peters, A, Vlieg, AV, McKnight, B, Psaty, BM, Hayward, C, Ward-Caviness, C, O'Donnell, C, Chasman, D, Strachan, DP, Tregouet, DA, Mook-Kanamori, D, Gill, D, Thibord, F, Asselbergs, FW, Leebeek, FWG, Rosendaal, FR, Davies, G, Homuth, G, Temprano, G, Campbell, H, Taylor, HA, Bressler, J, Huffman, JE, Rotter, JI, Yao, J, Wilson, JF, Bis, JC, Hahn, JM, Desch, KC, Wiggins, KL, Raffield, LM, Bielak, LF, Yanek, LR, Kleber, ME, Mueller, M, Kavousi, M, Mangino, M, Conomos, MP, Liu, ML, Brown, MR, Jhun, MA, Chen, MH, de Maat, MPM, Peyser, PA, Elliot, P, Wei, P, Wild, PS, Morange, PE, van der Harst, P, Yang, Q, Le, NQ, Marioni, R, Li, RF, Damrauer, SM, Cox, SR, Trompet, S, Felix, SB, Volker, U, Koenig, W, Jukema, JW, Guo, XQ, Gelinas, AD, Schneider, DJ, Janjic, N, Samani, NJ, Ye, S, Summers, C, Chilvers, ER, Danesh, J, and Paul, DS
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- 2022
10. Genome-wide analysis of over 106000 individuals identifies 9 neuroticism-associated loci
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Smith, D J, Escott-Price, V, Davies, G, Bailey, M ES, Colodro-Conde, L, Ward, J, Vedernikov, A, Marioni, R, Cullen, B, Lyall, D, Hagenaars, S P, Liewald, D CM, Luciano, M, Gale, C R, Ritchie, S J, Hayward, C, Nicholl, B, Bulik-Sullivan, B, Adams, M, Couvy-Duchesne, B, Graham, N, Mackay, D, Evans, J, Smith, B H, Porteous, D J, Medland, S E, Martin, N G, Holmans, P, McIntosh, A M, Pell, J P, Deary, I J, and OʼDonovan, M C
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- 2016
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11. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N = 112151)
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Davies, G, Marioni, R E, Liewald, D C, Hill, W D, Hagenaars, S P, Harris, S E, Ritchie, S J, Luciano, M, Fawns-Ritchie, C, Lyall, D, Cullen, B, Cox, S R, Hayward, C, Porteous, D J, Evans, J, McIntosh, A M, Gallacher, J, Craddock, N, Pell, J P, Smith, D J, Gale, C R, and Deary, I J
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- 2016
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12. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N = 53 949)
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Davies, G, Armstrong, N, Bis, J C, Bressler, J, Chouraki, V, Giddaluru, S, Hofer, E, Ibrahim-Verbaas, C A, Kirin, M, Lahti, J, van der Lee, S J, Le Hellard, S, Liu, T, Marioni, R E, Oldmeadow, C, Postmus, I, Smith, A V, Smith, J A, Thalamuthu, A, Thomson, R, Vitart, V, Wang, J, Yu, L, Zgaga, L, Zhao, W, Boxall, R, Harris, S E, Hill, W D, Liewald, D C, Luciano, M, Adams, H, Ames, D, Amin, N, Amouyel, P, Assareh, A A, Au, R, Becker, J T, Beiser, A, Berr, C, Bertram, L, Boerwinkle, E, Buckley, B M, Campbell, H, Corley, J, De Jager, P L, Dufouil, C, Eriksson, J G, Espeseth, T, Faul, J D, Ford, I, Scotland, Generation, Gottesman, R F, Griswold, M E, Gudnason, V, Harris, T B, Heiss, G, Hofman, A, Holliday, E G, Huffman, J, Kardia, S LR, Kochan, N, Knopman, D S, Kwok, J B, Lambert, J-C, Lee, T, Li, G, Li, S-C, Loitfelder, M, Lopez, O L, Lundervold, A J, Lundqvist, A, Mather, K A, Mirza, S S, Nyberg, L, Oostra, B A, Palotie, A, Papenberg, G, Pattie, A, Petrovic, K, Polasek, O, Psaty, B M, Redmond, P, Reppermund, S, Rotter, J I, Schmidt, H, Schuur, M, Schofield, P W, Scott, R J, Steen, V M, Stott, D J, van Swieten, J C, Taylor, K D, Trollor, J, Trompet, S, Uitterlinden, A G, Weinstein, G, Widen, E, Windham, B G, Jukema, J W, Wright, A F, Wright, M J, Yang, Q, Amieva, H, Attia, J R, Bennett, D A, Brodaty, H, de Craen, A JM, Hayward, C, Ikram, M A, Lindenberger, U, Nilsson, L-G, Porteous, D J, Räikkönen, K, Reinvang, I, Rudan, I, Sachdev, P S, Schmidt, R, Schofield, P R, Srikanth, V, Starr, J M, Turner, S T, Weir, D R, Wilson, J F, van Duijn, C, Launer, L, Fitzpatrick, A L, Seshadri, S, Mosley, TH, Jr, and Deary, I J
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- 2015
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13. Association between anticholinergic burden and dementia in UK Biobank
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Mur, J., primary, Russ, T.C., additional, Cox, S. R., additional, Marioni, R. E., additional, and Muniz-Terrera, G., additional
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- 2021
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14. Right ventricular failure after heart transplantation: relationship with preoperative haemodynamic parameters
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Campana, C., Gavazzi, A., Marioni, R., Montemartini, C., D’Armini, A., Pederzolli, N., Martinelli, L., Vigano, M., Larizza, C., Berzuini, C., Kootstra, Gauke, editor, Opelz, Gerhard, editor, Buurman, W. A., editor, van Hooff, J. P., editor, MacMaster, P., editor, and Wallwork, J., editor
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- 1992
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15. Meta-analyses identify DNA methylation associated with kidney function and damage
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Schlosser, P. (Pascal), Tin, A. (Adrienne), Matias-Garcia, P. R. (Pamela R.), Thio, C. H. (Chris H. L.), Joehanes, R. (Roby), Liu, H. (Hongbo), Weihs, A. (Antoine), Yu, Z. (Zhi), Hoppmann, A. (Anselm), Grundner-Culemann, F. (Franziska), Min, J. L. (Josine L.), Adeyemo, A. A. (Adebowale A.), Agyemang, C. (Charles), Arnlov, J. (Johan), Aziz, N. A. (Nasir A.), Baccarelli, A. (Andrea), Bochud, M. (Murielle), Brenner, H. (Hermann), Breteler, M. M. (Monique M. B.), Carmeli, C. (Cristian), Chaker, L. (Layal), Chambers, J. C. (John C.), Cole, S. A. (Shelley A.), Coresh, J. (Josef), Corre, T. (Tanguy), Correa, A. (Adolfo), Cox, S. R. (Simon R.), de Klein, N. (Niek), Delgado, G. E. (Graciela E.), Domingo-Relloso, A. (Arce), Eckardt, K.-U. (Kai-Uwe), Ekici, A. B. (Arif B.), Endlich, K. (Karlhans), Evans, K. L. (Kathryn L.), Floyd, J. S. (James S.), Fornage, M. (Myriam), Franke, L. (Lude), Fraszczyk, E. (Eliza), Gao, X. (Xu), Gao, X. (Xin), Ghanbari, M. (Mohsen), Ghasemi, S. (Sahar), Gieger, C. (Christian), Greenland, P. (Philip), Grove, M. L. (Megan L.), Harris, S. E. (Sarah E.), Hemani, G. (Gibran), Henneman, P. (Peter), Herder, C. (Christian), Horvath, S. (Steve), Hou, L. (Lifang), Hurme, M. A. (Mikko A.), Hwang, S.-J. (Shih-Jen), Järvelin, M.-R. (Marjo-Riitta), Kardia, S. L. (Sharon L. R.), Kasela, S. (Silva), Kleber, M. E. (Marcus E.), Koenig, W. (Wolfgang), Kooner, J. S. (Jaspal S.), Kramer, H. (Holly), Kronenberg, F. (Florian), Kuhnel, B. (Brigitte), Lehtimaki, T. (Terho), Lind, L. (Lars), Liu, D. (Dan), Liu, Y. (Yongmei), Lloyd-Jones, D. M. (Donald M.), Lohman, K. (Kurt), Lorkowski, S. (Stefan), Lu, A. T. (Ake T.), Marioni, R. E. (Riccardo E.), Marz, W. (Winfried), McCartney, D. L. (Daniel L.), Meeks, K. A. (Karlijn A. C.), Milani, L. (Lili), Mishra, P. P. (Pashupati P.), Nauck, M. (Matthias), Navas-Acien, A. (Ana), Nowak, C. (Christoph), Peters, A. (Annette), Prokisch, H. (Holger), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Ratliff, S. M. (Scott M.), Reiner, A. P. (Alex P.), Rosas, S. E. (Sylvia E.), Schottker, B. (Ben), Schwartz, J. (Joel), Sedaghat, S. (Sanaz), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Stocker, H. R. (Hannah R.), Stringhini, S. (Silvia), Sundstrom, J. (Johan), Swenson, B. R. (Brenton R.), Tellez-Plaza, M. (Maria), van Meurs, J. B. (Joyce B. J.), van Vliet-Ostaptchouk, J. V. (Jana V.), Venema, A. (Andrea), Verweij, N. (Niek), Walker, R. M. (Rosie M.), Wielscher, M. (Matthias), Winkelmann, J. (Juliane), Wolffenbuttel, B. H. (Bruce H. R.), Zhao, W. (Wei), Zheng, Y. (Yinan), Loh, M. (Marie), Snieder, H. (Harold), Levy, D. (Daniel), Waldenberger, M. (Melanie), Susztak, K. (Katalin), Kottgen, A. (Anna), Teumer, A. (Alexander), Schlosser, P. (Pascal), Tin, A. (Adrienne), Matias-Garcia, P. R. (Pamela R.), Thio, C. H. (Chris H. L.), Joehanes, R. (Roby), Liu, H. (Hongbo), Weihs, A. (Antoine), Yu, Z. (Zhi), Hoppmann, A. (Anselm), Grundner-Culemann, F. (Franziska), Min, J. L. (Josine L.), Adeyemo, A. A. (Adebowale A.), Agyemang, C. (Charles), Arnlov, J. (Johan), Aziz, N. A. (Nasir A.), Baccarelli, A. (Andrea), Bochud, M. (Murielle), Brenner, H. (Hermann), Breteler, M. M. (Monique M. B.), Carmeli, C. (Cristian), Chaker, L. (Layal), Chambers, J. C. (John C.), Cole, S. A. (Shelley A.), Coresh, J. (Josef), Corre, T. (Tanguy), Correa, A. (Adolfo), Cox, S. R. (Simon R.), de Klein, N. (Niek), Delgado, G. E. (Graciela E.), Domingo-Relloso, A. (Arce), Eckardt, K.-U. (Kai-Uwe), Ekici, A. B. (Arif B.), Endlich, K. (Karlhans), Evans, K. L. (Kathryn L.), Floyd, J. S. (James S.), Fornage, M. (Myriam), Franke, L. (Lude), Fraszczyk, E. (Eliza), Gao, X. (Xu), Gao, X. (Xin), Ghanbari, M. (Mohsen), Ghasemi, S. (Sahar), Gieger, C. (Christian), Greenland, P. (Philip), Grove, M. L. (Megan L.), Harris, S. E. (Sarah E.), Hemani, G. (Gibran), Henneman, P. (Peter), Herder, C. (Christian), Horvath, S. (Steve), Hou, L. (Lifang), Hurme, M. A. (Mikko A.), Hwang, S.-J. (Shih-Jen), Järvelin, M.-R. (Marjo-Riitta), Kardia, S. L. (Sharon L. R.), Kasela, S. (Silva), Kleber, M. E. (Marcus E.), Koenig, W. (Wolfgang), Kooner, J. S. (Jaspal S.), Kramer, H. (Holly), Kronenberg, F. (Florian), Kuhnel, B. (Brigitte), Lehtimaki, T. (Terho), Lind, L. (Lars), Liu, D. (Dan), Liu, Y. (Yongmei), Lloyd-Jones, D. M. (Donald M.), Lohman, K. (Kurt), Lorkowski, S. (Stefan), Lu, A. T. (Ake T.), Marioni, R. E. (Riccardo E.), Marz, W. (Winfried), McCartney, D. L. (Daniel L.), Meeks, K. A. (Karlijn A. C.), Milani, L. (Lili), Mishra, P. P. (Pashupati P.), Nauck, M. (Matthias), Navas-Acien, A. (Ana), Nowak, C. (Christoph), Peters, A. (Annette), Prokisch, H. (Holger), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Ratliff, S. M. (Scott M.), Reiner, A. P. (Alex P.), Rosas, S. E. (Sylvia E.), Schottker, B. (Ben), Schwartz, J. (Joel), Sedaghat, S. (Sanaz), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Stocker, H. R. (Hannah R.), Stringhini, S. (Silvia), Sundstrom, J. (Johan), Swenson, B. R. (Brenton R.), Tellez-Plaza, M. (Maria), van Meurs, J. B. (Joyce B. J.), van Vliet-Ostaptchouk, J. V. (Jana V.), Venema, A. (Andrea), Verweij, N. (Niek), Walker, R. M. (Rosie M.), Wielscher, M. (Matthias), Winkelmann, J. (Juliane), Wolffenbuttel, B. H. (Bruce H. R.), Zhao, W. (Wei), Zheng, Y. (Yinan), Loh, M. (Marie), Snieder, H. (Harold), Levy, D. (Daniel), Waldenberger, M. (Melanie), Susztak, K. (Katalin), Kottgen, A. (Anna), and Teumer, A. (Alexander)
- Abstract
Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
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- 2021
16. Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.
- Author
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UK Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Cancer Research UK Programme, Wellcome Trust and the Royal Society, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, Royal Netherlands Academy of Sciences, Economic and Social Research Council (grant no. ES/N000404/1), Austrian Academy of Sciences, Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, René, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Aldredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Söderhäll, C., Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalita, Mandaviya, Pooja, Zeng, Yanni, Clarke, Toni-Kim, Walker, Rosie M., Schmoll, V., Czamara, D., Ruiz-Arenas, Carlos, Rezwan, F. I., Marioni, R. E., Lin, T., Awaloff, Y., Barturen, G., Català-Moll, Frances, Kerick, Martin, Jiménez-Conde, Jordi, Roquer, Jaume, Gonzalez, Juan Ramón, Bustamante, Mariona, Sunyer, Jordi, Alarcón-Riquelme, Marta, UK Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Cancer Research UK Programme, Wellcome Trust and the Royal Society, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, Royal Netherlands Academy of Sciences, Economic and Social Research Council (grant no. ES/N000404/1), Austrian Academy of Sciences, Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, René, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Aldredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Söderhäll, C., Soriano-Tárraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalita, Mandaviya, Pooja, Zeng, Yanni, Clarke, Toni-Kim, Walker, Rosie M., Schmoll, V., Czamara, D., Ruiz-Arenas, Carlos, Rezwan, F. I., Marioni, R. E., Lin, T., Awaloff, Y., Barturen, G., Català-Moll, Frances, Kerick, Martin, Jiménez-Conde, Jordi, Roquer, Jaume, Gonzalez, Juan Ramón, Bustamante, Mariona, Sunyer, Jordi, and Alarcón-Riquelme, Marta
- Abstract
Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated.
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- 2021
17. O3-4.2 Cognitive reserve and cognitive decline: are individual sub-components of reserve driving the associations?
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Marioni, R, A van den Hout, Valenzuela, M, Brayne, C, and Matthews, F
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- 2011
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18. Increase in anticholinergic burden in the UK from 1990 to 2015: a UK Biobank study
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Mur, J., primary, Cox, S. R., additional, Marioni, R. E., additional, Muniz-Terrera, G., additional, and Russ, T. C., additional
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- 2020
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19. A combined analysis of genetically correlated traits identifies 187 loci and a role for neurogenesis and myelination in intelligence
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Hill, W. D., Marioni, R. E., Maghzian, O., Ritchie, S. J., Hagenaars, S. P., McIntosh, A. M., Gale, C. R., Davies, G., and Deary, I. J.
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Data Analysis ,Male ,Multifactorial Inheritance ,Neurogenesis ,Intelligence ,Nerve Fibers, Myelinated ,Polymorphism, Single Nucleotide ,Cognition ,Genetic Loci ,Humans ,Female ,Genetic Predisposition to Disease ,Immediate Communication ,Genome-Wide Association Study - Abstract
Intelligence, or general cognitive function, is phenotypically and genetically correlated with many traits, including a wide range of physical, and mental health variables. Education is strongly genetically correlated with intelligence (rg = 0.70). We used these findings as foundations for our use of a novel approach—multi-trait analysis of genome-wide association studies (MTAG; Turley et al. 2017)—to combine two large genome-wide association studies (GWASs) of education and intelligence, increasing statistical power and resulting in the largest GWAS of intelligence yet reported. Our study had four goals: first, to facilitate the discovery of new genetic loci associated with intelligence; second, to add to our understanding of the biology of intelligence differences; third, to examine whether combining genetically correlated traits in this way produces results consistent with the primary phenotype of intelligence; and, finally, to test how well this new meta-analytic data sample on intelligence predicts phenotypic intelligence in an independent sample. By combining datasets using MTAG, our functional sample size increased from 199,242 participants to 248,482. We found 187 independent loci associated with intelligence, implicating 538 genes, using both SNP-based and gene-based GWAS. We found evidence that neurogenesis and myelination—as well as genes expressed in the synapse, and those involved in the regulation of the nervous system—may explain some of the biological differences in intelligence. The results of our combined analysis demonstrated the same pattern of genetic correlations as those from previous GWASs of intelligence, providing support for the meta-analysis of these genetically-related phenotypes.
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- 2018
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20. Associations between polymorphisms in five inflammation-related genes and cognitive ability in older persons
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Marioni, R. E., Deary, I. J., Murray, G. D., Fowkes, F. G. R., and Price, J. F.
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- 2010
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21. Association between self-reported alcohol consumption (SAC) and cognitive ability in older people with Type 2 diabetes; the Edinburgh Type 2 diabetes study: A13 (P414)
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Conaglen, P D, Morling, J R, Williamson, R M, Marioni, R E, Deary, I J, Strachan, M WJ, and Price, J F
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- 2010
22. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
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Davies, G., Lam, M., Harris, S. E., TRAMPUSH, J. W., LUCIANO, M., HILL, W. D., HAGENAARS, S. P., RITCHIE, S. J., MARIONI, R. E., FAWNS-RITCHIE, C., LIEWALD, D. C. M., OKELY, J. A., AHOLA-OLLI, A. V., BARNES, C. L. K., Bertram, L., BIS, J. C., BURDICK, K. E., CHRISTOFOROU, A., DEROSSE, P., Djurovic, S., ESPESETH, T., GIAKOUMAKI, S., GIDDALURU, S., GUSTAVSON, D. E., Hayward, C., Hofer, E., KARLSSON, R., KNOWLES, E., Lahti, J., Leber, M., MATHER, K. A., Melle, I., Morris, D., OLDMEADOW, C., PALVIAINEN, T., PAYTON, A., PAZOKI, R., PETROVIC, K., Reynolds, C. A., SARGURUPREMRAJ, M., Scholz, M., Smith, J. A., SMITH, A. V., TERZIKHAN, N., THALAMUTHU, A., TROMPET, S., VAN DER LEE, S. J., WARE, E. B., WINDHAM, B. G., WRIGHT, M. J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., ANDREASSEN, O. A., ARMSTRONG, N. J., ASSAREH, A. A., ATTIA, J. R., ATTIX, D., AVRAMOPOULOS, D., BENNETT, D. A., BOHMER, A. C., BOYLE, P. A., BRODATY, H., Campbell, H., CANNON, T. D., CIRULLI, E. T., CONGDON, E., CONLEY, E. D., CORLEY, J., COX, S. R., DALE, A. M., DEHGHAN, A., Dick, D., Dickinson, D., ERIKSSON, J. G., EVANGELOU, E., FAUL, J. D., Ford, I., FREIMER, N. A., Gao, H., Giegling, I., GILLESPIE, N. A., GORDON, S. D., GOTTESMAN, R. F., GRISWOLD, M. E., GUDNASON, V., HARRIS, T. B., HARTMANN, A. M., Hatzimanolis, A., Heiss, G., HOLLIDAY, E. G., Joshi, P. K., KAHONEN, M., KARDIA, S. L. R., KARLSSON, I., KLEINEIDAM, L., KNOPMAN, D. S., KOCHAN, N. A., Konte, B., KWOK, J. B., LE HELLARD, S., Lee, T., LEHTIMAKI, T., Li, S. C., Lill, C. M., Liu, T., KOINI, M., London, E., LONGSTRETH, W. T., Jr., LOPEZ, O. L., LOUKOLA, A., LUCK, T., LUNDERVOLD, A. J., LUNDQUIST, A., LYYTIKAINEN, L. P., Martin, N. G., MONTGOMERY, G. W., MURRAY, A. D., NEED, A. C., NOORDAM, R., Nyberg, L., OLLIER, W., PAPENBERG, G., PATTIE, A., POLASEK, O., POLDRACK, R. A., PSATY, B. M., REPPERMUND, S., RIEDEL-HELLER, S. G., ROSE, R. J., ROTTER, J. I., ROUSSOS, P., ROVIO, S. P., SABA, Y., SABB, F. W., SACHDEV, P. S., SATIZABAL, C. L., Schmid, M., Scott, R. J., SCULT, M. A., SIMINO, J., SLAGBOOM, P. E., SMYRNIS, N., Soumare, A., Stefanis, N. C., STOTT, D. J., STRAUB, R. E., SUNDET, K., Taylor, A. M., TAYLOR, K. D., TZOULAKI, I., Tzourio, C., Uitterlinden, A., Vitart, V., VOINESKOS, A. N., Kaprio, J., Wagner, M., Wagner, H., WEINHOLD, L., WEN, K. H., WIDEN, E., Yang, Q., Zhao, W., ADAMS, H. H. H., ARKING, D. E., Bilder, R. M., BITSIOS, P., BOERWINKLE, E., CHIBA-FALEK, O., Corvin, A., DE JAGER, P. L., Debette, S., Donohoe, G., Elliott, P., FITZPATRICK, A. L., Gill, M., GLAHN, D. C., HAGG, S., HANSELL, N. K., HARIRI, A. R., Ikram, M. A., JUKEMA, J. W., VUOKSIMAA, E., KELLER, M. C., KREMEN, W. S., LAUNER, L., LINDENBERGER, U., Palotie, A., PEDERSEN, N. L., PENDLETON, N., PORTEOUS, D. J., RAIKKONEN, K., RAITAKARI, O. T., Ramirez, A., REINVANG, I., RUDAN, I., DAN, Rujescu, Schmidt, R., Schmidt, H., SCHOFIELD, P. W., STARR, J. M., STEEN, V. M., TROLLOR, J. N., TURNER, S. T., VAN DUIJN, C. M., VILLRINGER, A., WEINBERGER, D. R., WEIR, D. R., WILSON, J. F., Malhotra, A., MCINTOSH, A. M., GALE, C. R., SESHADRI, S., MOSLEY, T. H., Jr., BRESSLER, J., Lencz, T., DEARY, I. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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VINTAGE ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,HEALTHY ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) - Abstract
Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.
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- 2019
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23. Erratum: Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci
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Smith, D J, Escott-Price, V, Davies, G, Bailey, M E S, Colodro-Conde, L, Ward, J, Vedernikov, A, Marioni, R, Cullen, B, Lyall, D, Hagenaars, S P, Liewald, D C M, Luciano, M, Gale, C R, Ritchie, S J, Hayward, C, Nicholl, B, Bulik-Sullivan, B, Adams, M, Couvy-Duchesne, B, Graham, N, Mackay, D, Evans, J, Smith, B H, Porteous, D J, Medland, S E, Martin, N G, Holmans, P, McIntosh, A M, Pell, J P, Deary, I J, and O'Donovan, M C
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- 2016
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24. Serum angiotensin-converting enzyme and frequency of severe hypoglycaemia in Type 1 diabetes: does a relationship exist?
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Zammitt, N. N., Geddes, J., Warren, R. E., Marioni, R., Ashby, J. P., and Frier, B. M.
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- 2007
25. Nat Commun
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Franceschini, N., GIAMBARTOLOMEI, C., DE VRIES, P. S., FINAN, C., BIS, J. C., HUNTLEY, R. P., LOVERING, R. C., TAJUDDIN, S. M., WINKLER, T. W., GRAFF, M., KAVOUSI, M., Dale, C., SMITH, A. V., Hofer, E., VAN LEEUWEN, E. M., Nolte, I. M., Lu, L., Scholz, M., Sargurupremraj, Muralidharan, PITKANEN, N., FRANZEN, O., Joshi, P. K., NOORDAM, R., MARIONI, R. E., Hwang, S. J., MUSANI, S. K., SCHMINKE, U., PALMAS, W., ISAACS, A., CORREA, A., ZONDERMAN, A. B., Hofman, A., TEUMER, A., COX, A. J., UITTERLINDEN, A. G., Wong, A., SMIT, A. J., NEWMAN, A. B., Britton, A., RUUSALEPP, A., Sennblad, B., HEDBLAD, B., PASANIUC, B., PENNINX, B. W., LANGEFELD, C. D., WASSEL, C. L., Tzourio, Christophe, Fava, C., BALDASSARRE, D., O'LEARY, D. H., TEUPSER, D., Kuh, D., TREMOLI, E., MANNARINO, E., Grossi, E., BOERWINKLE, E., SCHADT, E. E., INGELSSON, E., VEGLIA, F., Rivadeneira, F., BEUTNER, F., Chauhan, Ganesh, Heiss, G., SNIEDER, H., Campbell, H., VOLZKE, H., MARKUS, H. S., DEARY, I. J., JUKEMA, J. W., de Graaf, J., Price, J., POTT, J., HOPEWELL, J. C., Liang, J., Thiery, J., Engmann, J., GERTOW, K., Rice, K., TAYLOR, K. D., DHANA, K., KIEMENEY, Lalm, LIND, L., RAFFIELD, L. M., LAUNER, L. J., HOLDT, L. M., DORR, M., DICHGANS, M., TRAYLOR, M., SITZER, M., KUMARI, M., Kivimaki, M., Nalls, M. A., MELANDER, O., RAITAKARI, O., FRANCO, O. H., RUEDA-OCHOA, O. L., ROUSSOS, P., WHINCUP, P. H., Amouyel, P., Giral, P., ANUGU, P., WONG, Q., Malik, R., RAURAMAA, R., BURKHARDT, R., Hardy, R., Schmidt, R., DE MUTSERT, R., MORRIS, R. W., STRAWBRIDGE, R. J., WANNAMETHEE, S. G., HAGG, S., Shah, S., MCLACHLAN, S., TROMPET, S., SESHADRI, S., KURL, S., HECKBERT, S. R., Ring, S., HARRIS, T. B., LEHTIMAKI, T., GALESLOOT, T. E., Shah, T., DE FAIRE, U., Plagnol, V., ROSAMOND, W. D., Post, W., Zhu, X., Zhang, X., Guo, X., SABA, Y., DEHGHAN, A., SELDENRIJK, A., MORRISON, A. C., HAMSTEN, A., PSATY, B. M., VAN DUIJN, C. M., LAWLOR, D. A., MOOK-KANAMORI, D. O., BOWDEN, D. W., Schmidt, H., WILSON, J. F., ROTTER, J. I., WARDLAW, J. M., DEANFIELD, J., HALCOX, J., LYYTIKAINEN, L. P., Loeffler, M., EVANS, M. K., Debette, Stéphanie, HUMPHRIES, S. E., VOLKER, U., GUDNASON, V., HINGORANI, A. D., BJORKEGREN, J. L. M., CASAS, J. P., O'DONNELL, C. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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VINTAGE ,cardiovascular system ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,cardiovascular diseases ,HEALTHY - Abstract
Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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- 2018
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26. A DNA methylation biomarker of alcohol consumption
- Author
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Liu, C, Marioni, R E, Hedman, Åsa K, Pfeiffer, L, Tsai, P-C, Reynolds, L M, Just, A C, Duan, Q, Boer, C G, Tanaka, T, Elks, C E, Aslibekyan, S, Brody, J A, Kühnel, B, Herder, C, Almli, L M, Zhi, D, Wang, Y, Huan, T, Yao, C, Mendelson, M M, Joehanes, R, Liang, L, Love, S-A, Guan, W, Shah, S, McRae, A F, Kretschmer, A, Prokisch, H, Strauch, K, Peters, A, Visscher, P M, Wray, N R, Guo, X, Wiggins, K L, Smith, A K, Binder, E B, Ressler, K J, Irvin, M R, Absher, D M, Hernandez, D, Ferrucci, L, Bandinelli, S, Lohman, K, Ding, J, Trevisi, L, Gustafsson, Stefan, Sandling, Johanna K., Stolk, L, Uitterlinden, A G, Yet, I, Castillo-Fernandez, J E, Spector, T D, Schwartz, J D, Vokonas, P, Lind, Lars, Li, Y, Fornage, M, Arnett, D K, Wareham, N J, Sotoodehnia, N, Ong, K K, van Meurs, J B J, Conneely, K N, Baccarelli, A A, Deary, I J, Bell, J T, North, K E, Liu, Y, Waldenberger, M, London, S J, Ingelsson, Erik, Levy, D, Wareham, Nicholas [0000-0003-1422-2993], Ong, Kenneth [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Erasmus MC other, Internal Medicine, and Epidemiology
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Adult ,Male ,Alcohol Drinking ,Ethanol ,Black People ,DNA Methylation ,Middle Aged ,White People ,Epigenesis, Genetic ,Annan medicinsk grundvetenskap ,Genetics ,Humans ,CpG Islands ,Female ,Other Basic Medicine ,Alcohol-Related Disorders ,Biomarkers ,Aged ,Genome-Wide Association Study - Abstract
The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted PDe tio första författarna delar på förstaförfattarskapet. De sex sista författarna delar på sistaförfattarskapet.
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- 2018
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27. DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation
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Richard, MA, Huan, T, Ligthart, S, Gondalia, R, Jhun, MA, Brody, JA, Irvin, MR, Marioni, R, Shen, J, Tsai, PC, Montasser, ME, Jia, Y, Syme, C, Salfati, EL, Boerwinkle, E, Guan, W, Mosley, TH, Bressler, J, Morrison, AC, Liu, C, Mendelson, MM, Uitterlinden, AG, van Meurs, JB, Heijmans, BT, ’t Hoen, PAC, van Meurs, J, Isaacs, A, Jansen, R, Franke, L, Boomsma, DI, Pool, R, van Dongen, J, Hottenga, JJ, van Greevenbroek, MMJ, Stehouwer, CDA, van der Kallen, CJH, Schalkwijk, CG, Wijmenga, C, Zhernakova, A, Tigchelaar, EF, Slagboom, PE, Beekman, M, Deelen, J, van Heemst, D, Veldink, JH, van den Berg, LH, van Duijn, CM, Hofman, A, Jhamai, PM, Verbiest, M, Suchiman, HED, Verkerk, M, van der Breggen, R, van Rooij, J, Lakenberg, N, Mei, H, van Iterson, M, van Galen, M, Bot, J, van ’t Hof, P, Deelen, P, Nooren, I, Moed, M, Vermaat, M, Zhernakova, DV, Luijk, R, Bonder, MJ, van Dijk, F, Arindrarto, W, Kielbasa, SM, Swertz, MA, van Zwet, EW, Franco, OH, Zhang, G, Li, Y, Stewart, JD, Bis, JC, Psaty, BM, Chen, YDI, Kardia, SLR, Zhao, W, Turner, ST, Absher, D, Aslibekyan, S, and Starr, JM
- Abstract
© 2017 American Society of Human Genetics Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p < 1.0 × 10−7; replication: N = 7,182, p < 1.6 × 10−3). The replicated methylation sites are heritable (h2 > 30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants.
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- 2017
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28. An epigenome-wide association study meta-analysis of educational attainment
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Karlsson Linnér, R, Marioni, R E, Rietveld, C A, Simpkin, A J, Davies, N M, Watanabe, K, Armstrong, N J, Auro, K, Baumbach, C, Bonder, M J, Buchwald, J, Fiorito, G, Ismail, K, Iurato, S, Joensuu, A, Karell, P, Kasela, S, Lahti, J, McRae, A F, Mandaviya, P R, Seppälä, I, Wang, Y, Baglietto, L, Binder, E B, Harris, S E, Hodge, A M, Horvath, S, Hurme, M, Johannesson, M, Latvala, A, Mather, K A, Medland, S E, Metspalu, A, Milani, L, Milne, R L, Pattie, A, Pedersen, N L, Peters, A, Polidoro, S, Räikkönen, K, Severi, G, Starr, J M, Stolk, L, Waldenberger, M, Eriksson, J G, Esko, T, Franke, L, Gieger, C, Relton, C, Davey Smith, G, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Department of Health and Life Sciences, and Stem Cell Aging Leukemia and Lymphoma (SALL)
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EPIGENETIC CLOCK ,AGE ,STRESS ,TISSUE ,MORTALITY ,PATTERNS ,SOCIOECONOMIC-STATUS ,MATERNAL SMOKING ,EXPOSURE ,DNA METHYLATION - Abstract
The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications-in our case, CpG methylation-and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.Molecular Psychiatry advance online publication, 31 October 2017; doi:10.1038/mp.2017.210.
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- 2017
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29. Association of methylation signals with incident coronary heart disease in an epigenome-wide assessment of circulating tumor necrosis factor α
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Aslibekyan, S. (Stella), Agha, G. (Golareh), Colicino, E. (Elena), Do, A. N. (Anh N.), Lahti, J. (Jari), Ligthart, S. (Symen), Marioni, R. E. (Riccardo E.), Marzi, C. (Carola), Mendelson, M. M. (Michael M.), Tanaka, T. (Toshiko), Wielscher, M. (Matthias), Absher, D. M. (Devin M.), Ferrucci, L. (Luigi), Franco, O. H. (Oscar H.), Gieger, C. (Christian), Grallert, H. (Harald), Hernandez, D. (Dena), Huan, T. (Tianxiao), Iurato, S. (Stella), Joehanes, R. (Roby), Just, A. C. (Allan C.), Kunze, S. (Sonja), Lin, H. (Honghuang), Liu, C. (Chunyu), Meigs, J. B. (James B.), van Meurs, J. B. (Joyce B.J.), Moore, A. Z. (Ann Zenobia), Peters, A. (Annette), Prokisch, H. (Holger), Räikkönen, K. (Katri), Rathmann, W. (Wolfgang), Roden, M. (Michael), Schramm, K. (Katharina), Schwartz, J. D. (Joel D.), Starr, J. M. (John M.), Uitterlinden, A. G. (André G.), Vokonas, P. (Pantel), Waldenberger, M. (Melanie), Yao, C. (Chen), Zhi, D. (Degui), Baccarelli, A. A. (Andrea A.), Bandinelli, S. (Stefania), Deary, I. J. (Ian J.), Dehghan, A. (Abbas), Eriksson, J. (Johan), Herder, C. (Christian), Järvelin, M.-R. (Marjo-Riitta), Levy, D. (Daniel), Arnett, D. K. (Donna K.), Aslibekyan, S. (Stella), Agha, G. (Golareh), Colicino, E. (Elena), Do, A. N. (Anh N.), Lahti, J. (Jari), Ligthart, S. (Symen), Marioni, R. E. (Riccardo E.), Marzi, C. (Carola), Mendelson, M. M. (Michael M.), Tanaka, T. (Toshiko), Wielscher, M. (Matthias), Absher, D. M. (Devin M.), Ferrucci, L. (Luigi), Franco, O. H. (Oscar H.), Gieger, C. (Christian), Grallert, H. (Harald), Hernandez, D. (Dena), Huan, T. (Tianxiao), Iurato, S. (Stella), Joehanes, R. (Roby), Just, A. C. (Allan C.), Kunze, S. (Sonja), Lin, H. (Honghuang), Liu, C. (Chunyu), Meigs, J. B. (James B.), van Meurs, J. B. (Joyce B.J.), Moore, A. Z. (Ann Zenobia), Peters, A. (Annette), Prokisch, H. (Holger), Räikkönen, K. (Katri), Rathmann, W. (Wolfgang), Roden, M. (Michael), Schramm, K. (Katharina), Schwartz, J. D. (Joel D.), Starr, J. M. (John M.), Uitterlinden, A. G. (André G.), Vokonas, P. (Pantel), Waldenberger, M. (Melanie), Yao, C. (Chen), Zhi, D. (Degui), Baccarelli, A. A. (Andrea A.), Bandinelli, S. (Stefania), Deary, I. J. (Ian J.), Dehghan, A. (Abbas), Eriksson, J. (Johan), Herder, C. (Christian), Järvelin, M.-R. (Marjo-Riitta), Levy, D. (Daniel), and Arnett, D. K. (Donna K.)
- Abstract
Importance: Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine with manifold consequences for mammalian pathophysiology, including cardiovascular disease. A deeper understanding of TNF-α biology may enhance treatment precision. Objective: To conduct an epigenome-wide analysis of blood-derived DNA methylation and TNF-α levels and to assess the clinical relevance of findings. Design, Setting, and Participants: This meta-analysis assessed epigenome-wide associations in circulating TNF-α concentrations from 5 cohort studies and 1 interventional trial, with replication in 3 additional cohort studies. Follow-up analyses investigated associations of identified methylation loci with gene expression and incident coronary heart disease; this meta-analysis included 11 461 participants who experienced 1895 coronary events. Exposures: Circulating TNF-α concentration. Main Outcomes and Measures: DNA methylation at approximately 450 000 loci, neighboring DNA sequence variation, gene expression, and incident coronary heart disease. Results: The discovery cohort included 4794 participants, and the replication study included 816 participants (overall mean [SD] age, 60.7 [8.5] years). In the discovery stage, circulating TNF-α levels were associated with methylation of 7 cytosine-phosphate-guanine (CpG) sites, 3 of which were located in or near DTX3L-PARP9 at cg00959259 (β [SE] = −0.01 [0.003]; P = 7.36×10⁻⁸), cg08122652 (β [SE] = −0.008 [0.002]; P = 2.24×10⁻⁷), and cg22930808(β [SE] = −0.01 [0.002]; P = 6.92×10⁻⁸); NLRC5 at cg16411857 (β [SE] = −0.01 [0.002]; P = 2.14×10⁻¹³) and cg07839457 (β [SE] = −0.02 [0.003]; P = 6.31×10⁻¹⁰); or ABO, at cg13683939 (β [SE] = 0.04 [0.008]; P = 1.42×10⁻⁷) and cg24267699 (β [SE] = −0.009 [0.002]; P = 1.67 × 10⁻⁷), after accounting for multiple testing. Of these, negative associations between TNF-α concentration and methylation of 2 loci in NLRC5 and 1 in DTX3L-14 PARP9 were replicated. Replicated TNF-α–linked CpG sites were associ
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- 2018
30. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
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Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., Hagenaars, S. P., Ritchie, S. J., Marioni, R. E., Fawns-Ritchie, C., Liewald, D. C. M., Okely, J. A., Ahola-Olli, A. V., Barnes, C. L. K., Bertram, L., Bis, J. C., Burdick, K. E., Christoforou, A., Derosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D. E., Hayward, C., Hofer, E., Ikram, M. A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K. A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C. A., Sargurupremraj, M., Scholz, M., Smith, J. A., Smith, A. V., Terzikhan, N., Thalamuthu, A., Trompet, S., Van Der Lee, S. J., Ware, E. B., Windham, B. G., Wright, M. J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O. A., Armstrong, N. J., Assareh, A. A., Attia, J. R., Attix, D., Avramopoulos, D., Bennett, D. A., Böhmer, A. C., Boyle, P. A., Brodaty, H., Campbell, H., Cannon, T. D., Cirulli, E. T., Congdon, E., Conley, E. D., Corley, J., Cox, S. R., Dale, A. M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J. G., Evangelou, E., Faul, J. D., Ford, I., Freimer, N. A., Gao, H., Giegling, I., Gillespie, N. A., Gordon, S. D., Gottesman, R. F., Griswold, M. E., Gudnason, V., Harris, T. B., Hartmann, A. M., Hatzimanolis, A., Heiss, G., Holliday, E. G., Joshi, P. K., Kähönen, M., Kardia, S. L. R., Karlsson, Ida K., Kleineidam, L., Knopman, D. S., Kochan, N. A., Konte, B., Kwok, J. B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S. -C, Liu, T., Koini, M., London, E., Longstreth, W.T., Jr., Lopez, O. L., Loukola, A., Luck, T., Lundervold, A. J., Lundquist, A., Lyytikäinen, L. -P, Martin, N. G., Montgomery, G. W., Murray, A. D., Need, A. C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R. A., Psaty, B. M., Reppermund, S., Riedel-Heller, S. G., Rose, R. J., Rotter, J. I., Roussos, P., Rovio, S. P., Saba, Y., Sabb, F. W., Sachdev, P. S., Satizabal, C. L., Schmid, M., Scott, R. J., Scult, M. A., Simino, J., Slagboom, P. E., Smyrnis, N., Soumaré, A., Stefanis, N. C., Stott, D. J., Straub, R. E., Sundet, K., Taylor, A. M., Taylor, K. D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A. N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K. H., Widen, E., Yang, Q., Zhao, W., Adams, H. H. H., Arking, D. E., Bilder, R. M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P. L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A. L., Gill, M., Glahn, D. C., Hägg, S., Hansell, N. K., Hariri, A. R., Ikram, M. K., Jukema, J. W., Vuoksimaa, E., Keller, M. C., Kremen, W. S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N. L., Pendleton, N., Porteous, D. J., Räikkönen, K., Raitakari, O. T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P. W., Schofield, P. R., Starr, J. M., Steen, V. M., Trollor, J. N., Turner, S. T., Van Duijn, C. M., Villringer, A., Weinberger, D. R., Weir, D. R., Wilson, J. F., Malhotra, A., McIntosh, A. M., Gale, C. R., Seshadri, S., Mosley, T.H., Jr., Bressler, J., Lencz, T., Deary, I. J., Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., Hagenaars, S. P., Ritchie, S. J., Marioni, R. E., Fawns-Ritchie, C., Liewald, D. C. M., Okely, J. A., Ahola-Olli, A. V., Barnes, C. L. K., Bertram, L., Bis, J. C., Burdick, K. E., Christoforou, A., Derosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D. E., Hayward, C., Hofer, E., Ikram, M. A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K. A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C. A., Sargurupremraj, M., Scholz, M., Smith, J. A., Smith, A. V., Terzikhan, N., Thalamuthu, A., Trompet, S., Van Der Lee, S. J., Ware, E. B., Windham, B. G., Wright, M. J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O. A., Armstrong, N. J., Assareh, A. A., Attia, J. R., Attix, D., Avramopoulos, D., Bennett, D. A., Böhmer, A. C., Boyle, P. A., Brodaty, H., Campbell, H., Cannon, T. D., Cirulli, E. T., Congdon, E., Conley, E. D., Corley, J., Cox, S. R., Dale, A. M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J. G., Evangelou, E., Faul, J. D., Ford, I., Freimer, N. A., Gao, H., Giegling, I., Gillespie, N. A., Gordon, S. D., Gottesman, R. F., Griswold, M. E., Gudnason, V., Harris, T. B., Hartmann, A. M., Hatzimanolis, A., Heiss, G., Holliday, E. G., Joshi, P. K., Kähönen, M., Kardia, S. L. R., Karlsson, Ida K., Kleineidam, L., Knopman, D. S., Kochan, N. A., Konte, B., Kwok, J. B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S. -C, Liu, T., Koini, M., London, E., Longstreth, W.T., Jr., Lopez, O. L., Loukola, A., Luck, T., Lundervold, A. J., Lundquist, A., Lyytikäinen, L. -P, Martin, N. G., Montgomery, G. W., Murray, A. D., Need, A. C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R. A., Psaty, B. M., Reppermund, S., Riedel-Heller, S. G., Rose, R. J., Rotter, J. I., Roussos, P., Rovio, S. P., Saba, Y., Sabb, F. W., Sachdev, P. S., Satizabal, C. L., Schmid, M., Scott, R. J., Scult, M. A., Simino, J., Slagboom, P. E., Smyrnis, N., Soumaré, A., Stefanis, N. C., Stott, D. J., Straub, R. E., Sundet, K., Taylor, A. M., Taylor, K. D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A. N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K. H., Widen, E., Yang, Q., Zhao, W., Adams, H. H. H., Arking, D. E., Bilder, R. M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., De Jager, P. L., Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A. L., Gill, M., Glahn, D. C., Hägg, S., Hansell, N. K., Hariri, A. R., Ikram, M. K., Jukema, J. W., Vuoksimaa, E., Keller, M. C., Kremen, W. S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N. L., Pendleton, N., Porteous, D. J., Räikkönen, K., Raitakari, O. T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P. W., Schofield, P. R., Starr, J. M., Steen, V. M., Trollor, J. N., Turner, S. T., Van Duijn, C. M., Villringer, A., Weinberger, D. R., Weir, D. R., Wilson, J. F., Malhotra, A., McIntosh, A. M., Gale, C. R., Seshadri, S., Mosley, T.H., Jr., Bressler, J., Lencz, T., and Deary, I. J.
- Abstract
General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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- 2018
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31. A DNA methylation biomarker of alcohol consumption
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Liu, C, Marioni, R E, Hedman, Å K, Pfeiffer, L, Tsai, P-C, Reynolds, L M, Just, A C, Duan, Q, Boer, C G, Tanaka, T, Elks, C E, Aslibekyan, S, Brody, J A, Kühnel, B, Herder, C, Almli, L M, Zhi, D, Wang, Y, Huan, T, Yao, C, Mendelson, M M, Joehanes, R, Liang, L, Love, S-A, Guan, W, Shah, S, McRae, A F, Kretschmer, A, Prokisch, H, Strauch, K, Peters, A, Visscher, P M, Wray, N R, Guo, X, Wiggins, K L, Smith, A K, Binder, E B, Ressler, K J, Irvin, M R, Absher, D M, Hernandez, D, Ferrucci, L, Bandinelli, S, Lohman, K, Ding, J, Trevisi, L, Gustafsson, S, Sandling, J H, Stolk, L, Uitterlinden, A G, Yet, I, Castillo-Fernandez, J E, Spector, T D, Schwartz, J D, Vokonas, P, Lind, L, Li, Y, Fornage, M, Arnett, D K, Wareham, N J, Sotoodehnia, N, Ong, K K, van Meurs, J B J, Conneely, K N, Baccarelli, A A, Deary, I J, Bell, J T, North, K E, Liu, Y, Waldenberger, M, London, S J, Ingelsson, E, and Levy, D
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ddc - Published
- 2016
32. Brain age predicts mortality
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Cole, J H, primary, Ritchie, S J, additional, Bastin, M E, additional, Valdés Hernández, M C, additional, Muñoz Maniega, S, additional, Royle, N, additional, Corley, J, additional, Pattie, A, additional, Harris, S E, additional, Zhang, Q, additional, Wray, N R, additional, Redmond, P, additional, Marioni, R E, additional, Starr, J M, additional, Cox, S R, additional, Wardlaw, J M, additional, Sharp, D J, additional, and Deary, I J, additional
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- 2017
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33. Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
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Hagg, S., Zhan, Y., Karlsson, R., Gerritsen, L., Ploner, A., van der Lee, S. J., Broer, L., Deelen, J., Marioni, R. E., Wong, A., Lundquist, Anders, Zhu, G., Hansell, N. K., Sillanpaa, E., Fedko, I. O., Amin, N. A., Beekman, M., de Craen, A. J. M., Degerman, Sofie, Harris, S. E., Kan, K-J, Martin-Ruiz, C. M., Montgomery, G. W., Adolfsson, Annelie N., Reynolds, C. A., Samani, N. J., Suchiman, H. E. D., Viljanen, A., von Zglinicki, T., Wright, M. J., Hottenga, J-J, Boomsma, D. I., Rantanen, T., Kaprio, J. A., Nyholt, D. R., Martin, N. G., Nyberg, Lars, Adolfsson, Rolf, Kuh, D., Starr, J. M., Deary, I. J., Slagboom, P. E., van Duijn, C. M., Codd, V., Pedersen, N. L., Hagg, S., Zhan, Y., Karlsson, R., Gerritsen, L., Ploner, A., van der Lee, S. J., Broer, L., Deelen, J., Marioni, R. E., Wong, A., Lundquist, Anders, Zhu, G., Hansell, N. K., Sillanpaa, E., Fedko, I. O., Amin, N. A., Beekman, M., de Craen, A. J. M., Degerman, Sofie, Harris, S. E., Kan, K-J, Martin-Ruiz, C. M., Montgomery, G. W., Adolfsson, Annelie N., Reynolds, C. A., Samani, N. J., Suchiman, H. E. D., Viljanen, A., von Zglinicki, T., Wright, M. J., Hottenga, J-J, Boomsma, D. I., Rantanen, T., Kaprio, J. A., Nyholt, D. R., Martin, N. G., Nyberg, Lars, Adolfsson, Rolf, Kuh, D., Starr, J. M., Deary, I. J., Slagboom, P. E., van Duijn, C. M., Codd, V., and Pedersen, N. L.
- Abstract
The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N = 17 052; mean age = 59.2 +/- 8.8 years) provided results for associations between qPCR-measuredTL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (beta = 0.051 per s. d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P = 0.0002), and MMSE (beta = 0.025; 95% CI: 0.002, 0.047; P = 0.03), and faster STROOP (beta = -0.053; 95% CI: -0.087, -0.018; P = 0.003). Effects for DSST were stronger in APOE epsilon 4 non-carriers (beta = 0.081; 95% CI: 0.045, 0.117; P = 1.0 x 10(-5)), whereas carriers performed better in STROOP (beta = -0.074; 95% CI: -0.140, -0.009; P = 0.03). Causal associations were found for STROOP only (beta = -0.598 per s. d.-increase of TL; 95% CI: -1.125, -0.072; P = 0.026), with a larger effect in epsilon 4-carriers (beta = -0.699; 95% CI: -1.330, -0.069; P = 0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE epsilon 4-carriers might be at differential risk.
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- 2017
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34. Heavier smoking may lead to a relative increase in waist circumference: Evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium
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Morris, R.W., Taylor, A.E., Fluharty, M.E., Bjorngaard, J.H., Asvold, B.O., Elvestad Gabrielsen, M., Campbell, A., Marioni, R., Kumari, M., Korhonen, T., Männistö, S., Marques-Vidal, P., Kaakinen, M., Cavadino, A., Postmus, I., Husemoen, L.L.N., Skaaby, T., Ahluwalia, T.S., Treur, J.L., Willemsen, G., Dale, C., Wannamethee, S.G., Lahti, J., Palotie, A., Räikkönen, K., McConnachie, A., Padmanabhan, S., Wong, A., Dalgard, C., Paternoster, L., Ben-Shlomo, Y., Tyrrell, J., Horwood, J., Fergusson, D.M., Kennedy, M.A., Nohr, E.A., Christiansen, L., Kyvik, K.O., Kuh, D, Watt, G., Eriksson, J.G., Whincup, P.H., Vink, J.M., Boomsma, D.I., Davey Smith, G., Lawlor, D., Linneberg, A., Ford, I., Jukema, J.W., Power, C., Hyppönen, E., Jarvelin, M.R., Preisig, M., Borodulin, K., Kaprio, J., Kivimaki, M., Smith, B.H., Hayward, C., Romundstad, P.R., Sørensen, T.I.A., Munafò, M., Sattar, N., Medical Research Council (MRC), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, and EMGO+ - Lifestyle, Overweight and Diabetes
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Adult ,Male ,Netherlands Twin Register (NTR) ,Adolescent ,GENETICS ,Aged ,Body Mass Index ,Female ,Humans ,Mendelian Randomization Analysis ,Middle Aged ,Obesity, Abdominal/complications ,Sex Factors ,Smoking/adverse effects ,Smoking/genetics ,Waist Circumference ,Waist-Hip Ratio ,Young Adult ,Brain and Behaviour ,Medicine, General & Internal ,SDG 3 - Good Health and Well-being ,General & Internal Medicine ,EPIDEMIOLOGY ,CORONARY-HEART-DISEASE ,WEIGHT CONCERNS ,Smoking and Tobacco ,Science & Technology ,MORTALITY ,Research ,Tobacco and Alcohol ,Smoking ,WOMEN ,MEN ,ASSOCIATION ,BODY-MASS INDEX ,Obesity, Abdominal ,RISK-FACTORS ,ADIPOSITY ,CIGARETTE-SMOKING ,Life Sciences & Biomedicine ,Developmental Psychopathology - Abstract
OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity.DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes.PARTICIPANTS: 148 731 current, former and never-smokers of European ancestry aged ≥16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio.RESULTS: The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele.CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity. OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity.DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes.PARTICIPANTS: 148 731 current, former and never-smokers of European ancestry aged ≥16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio.RESULTS: The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele.CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.
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- 2015
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35. Polygenic risk of ischemic stroke is associated with cognitive ability.
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Harris, SE, Malik, R, Marioni, R, Campbell, A, Seshadri, S, Worrall, BB, Sudlow, CLM, Hayward, C, Bastin, ME, Starr, JM, Porteous, DJ, Wardlaw, JM, Deary, IJ, METASTROKE Consortium, Harris, SE, Malik, R, Marioni, R, Campbell, A, Seshadri, S, Worrall, BB, Sudlow, CLM, Hayward, C, Bastin, ME, Starr, JM, Porteous, DJ, Wardlaw, JM, Deary, IJ, and METASTROKE Consortium
- Abstract
OBJECTIVES: We investigated the correlation between polygenic risk of ischemic stroke (and its subtypes) and cognitive ability in 3 relatively healthy Scottish cohorts: the Lothian Birth Cohort 1936 (LBC1936), the Lothian Birth Cohort 1921 (LBC1921), and Generation Scotland: Scottish Family Health Study (GS). METHODS: Polygenic risk scores for ischemic stroke were created in LBC1936 (n = 1005), LBC1921 (n = 517), and GS (n = 6,815) using genome-wide association study summary data from the METASTROKE collaboration. We investigated whether the polygenic risk scores correlate with cognitive ability in the 3 cohorts. RESULTS: In the largest cohort, GS, polygenic risk of all ischemic stroke, small vessel disease stroke, and large vessel disease stroke, but not cardioembolic stroke, were correlated with both fluid and crystallized cognitive abilities. The highest correlation was between a polygenic risk score for all ischemic stroke and general cognitive ability (r = -0.070, p = 1.95 × 10(-8)). Few correlations were identified in LBC1936 and LBC1921, but a meta-analysis of all 3 cohorts supported the correlation between polygenic risk of ischemic stroke and cognitive ability. CONCLUSIONS: The findings from this study indicate that even in the absence of stroke, being at high polygenic risk of ischemic stroke is associated with lower cognitive ability.
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- 2016
36. DNA methylation signatures of chronic low-grade inflammation are associated with complex diseases
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Ligthart, Symen, Marzi, C, Aslibekyan, S, Mendelson, MM, Conneely, KN, Tanaka, T, Colicino, E, Waite, LL, Joehanes, R, Guan, WH, Brody, JA, Elks, C, Marioni, R, Jhun, MA, Agha, G, Bressler, J, Ward-Caviness, CK, Chen, BH, Huan, TX, Bakulski, K, Salfati, EL, Wahl, S, Schramm, K, Sha, J, Hernandez, DG, Just, AC, Smith, JA, Sotoodehnia, N, Pilling, LC, Pankow, JS, Tsao, PS, Liu, CY, Zhao, W, Guarrera, S, Michopoulos, VJ, Smith, AK, Peters, Marjolein, Melzer, D, Vokonas, P, Fornage, M, Prokisch, H, Bis, JC, Chu, AY, Herder, Cindy, Grallert, H, Yao, C, Shah, S, Mcrae, AF, Lin, HH, Horvath, S, Fallin, D, Hofman, Bert, Wareham, NJ, Wiggins, KL, Feinberg, AP, Starr, JM, Visscher, PM, Murabito, JM, Kardia, SLR, Absher, DM, Binder, EB, Singleton, AB, Bandinelli, S, Peters, A, Waldenberger, M, Matullo, G, Schwartz, JD, Demerath, EW, Uitterlinden, André, van Meurs, Joyce, Franco Duran, OH, Chen, YDI, Levy, D, Turner, ST, Deary, IJ, Ressler, KJ, Dupuis, J, Ferrucci, L, Ong, KK, Assimes, TL, Boerwinkle, E, Koenig, W, Arnett, DK, Baccarelli, AA, Benjamin, EJ, Dehghan, Abbas, Ligthart, Symen, Marzi, C, Aslibekyan, S, Mendelson, MM, Conneely, KN, Tanaka, T, Colicino, E, Waite, LL, Joehanes, R, Guan, WH, Brody, JA, Elks, C, Marioni, R, Jhun, MA, Agha, G, Bressler, J, Ward-Caviness, CK, Chen, BH, Huan, TX, Bakulski, K, Salfati, EL, Wahl, S, Schramm, K, Sha, J, Hernandez, DG, Just, AC, Smith, JA, Sotoodehnia, N, Pilling, LC, Pankow, JS, Tsao, PS, Liu, CY, Zhao, W, Guarrera, S, Michopoulos, VJ, Smith, AK, Peters, Marjolein, Melzer, D, Vokonas, P, Fornage, M, Prokisch, H, Bis, JC, Chu, AY, Herder, Cindy, Grallert, H, Yao, C, Shah, S, Mcrae, AF, Lin, HH, Horvath, S, Fallin, D, Hofman, Bert, Wareham, NJ, Wiggins, KL, Feinberg, AP, Starr, JM, Visscher, PM, Murabito, JM, Kardia, SLR, Absher, DM, Binder, EB, Singleton, AB, Bandinelli, S, Peters, A, Waldenberger, M, Matullo, G, Schwartz, JD, Demerath, EW, Uitterlinden, André, van Meurs, Joyce, Franco Duran, OH, Chen, YDI, Levy, D, Turner, ST, Deary, IJ, Ressler, KJ, Dupuis, J, Ferrucci, L, Ong, KK, Assimes, TL, Boerwinkle, E, Koenig, W, Arnett, DK, Baccarelli, AA, Benjamin, EJ, and Dehghan, Abbas
- Abstract
Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation. Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 x 10(-7)) in the discovery panel of European ancestry and replicated (P < 2.29 x 10(-4)) 58 CpG sites (45 unique loci) among African Americans. To further characterize the molecular and clinical relevance of the findings, we examined the association with gene expression, genetic sequence variants, and clinical outcomes. DNA methylation at nine (16%) CpG sites was associated with whole blood gene expression in cis (P < 8.47 x 10(-5)), ten (17%) CpG sites were associated with a nearby genetic variant (P < 2.50 x 10(-3)), and 51 (88%) were also associated with at least one related cardiometabolic entity (P < 9.58x 10(-5)). An additive weighted score of replicated CpG sites accounted for up to 6% inter-individual variation (R-2) of age-adjusted and sex-adjusted CRP, independent of known CRP-related genetic variants. Conclusion: We have completed an EWAS of chronic low-grade inflammation and identified many novel genetic loci underlying inflammation that may serve as targets for the development of novel therapeutic interventions for inflammation.
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- 2016
37. A DNA methylation biomarker of alcohol consumption
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Liu, C, primary, Marioni, R E, additional, Hedman, Å K, additional, Pfeiffer, L, additional, Tsai, P-C, additional, Reynolds, L M, additional, Just, A C, additional, Duan, Q, additional, Boer, C G, additional, Tanaka, T, additional, Elks, C E, additional, Aslibekyan, S, additional, Brody, J A, additional, Kühnel, B, additional, Herder, C, additional, Almli, L M, additional, Zhi, D, additional, Wang, Y, additional, Huan, T, additional, Yao, C, additional, Mendelson, M M, additional, Joehanes, R, additional, Liang, L, additional, Love, S-A, additional, Guan, W, additional, Shah, S, additional, McRae, A F, additional, Kretschmer, A, additional, Prokisch, H, additional, Strauch, K, additional, Peters, A, additional, Visscher, P M, additional, Wray, N R, additional, Guo, X, additional, Wiggins, K L, additional, Smith, A K, additional, Binder, E B, additional, Ressler, K J, additional, Irvin, M R, additional, Absher, D M, additional, Hernandez, D, additional, Ferrucci, L, additional, Bandinelli, S, additional, Lohman, K, additional, Ding, J, additional, Trevisi, L, additional, Gustafsson, S, additional, Sandling, J H, additional, Stolk, L, additional, Uitterlinden, A G, additional, Yet, I, additional, Castillo-Fernandez, J E, additional, Spector, T D, additional, Schwartz, J D, additional, Vokonas, P, additional, Lind, L, additional, Li, Y, additional, Fornage, M, additional, Arnett, D K, additional, Wareham, N J, additional, Sotoodehnia, N, additional, Ong, K K, additional, van Meurs, J B J, additional, Conneely, K N, additional, Baccarelli, A A, additional, Deary, I J, additional, Bell, J T, additional, North, K E, additional, Liu, Y, additional, Waldenberger, M, additional, London, S J, additional, Ingelsson, E, additional, and Levy, D, additional
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- 2016
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38. Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci
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Smith, D J, primary, Escott-Price, V, additional, Davies, G, additional, Bailey, M E S, additional, Colodro-Conde, L, additional, Ward, J, additional, Vedernikov, A, additional, Marioni, R, additional, Cullen, B, additional, Lyall, D, additional, Hagenaars, S P, additional, Liewald, D C M, additional, Luciano, M, additional, Gale, C R, additional, Ritchie, S J, additional, Hayward, C, additional, Nicholl, B, additional, Bulik-Sullivan, B, additional, Adams, M, additional, Couvy-Duchesne, B, additional, Graham, N, additional, Mackay, D, additional, Evans, J, additional, Smith, B H, additional, Porteous, D J, additional, Medland, S E, additional, Martin, N G, additional, Holmans, P, additional, McIntosh, A M, additional, Pell, J P, additional, Deary, I J, additional, and O'Donovan, M C, additional
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- 2016
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39. Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)
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Davies, G, primary, Marioni, R E, additional, Liewald, D C, additional, Hill, W D, additional, Hagenaars, S P, additional, Harris, S E, additional, Ritchie, S J, additional, Luciano, M, additional, Fawns-Ritchie, C, additional, Lyall, D, additional, Cullen, B, additional, Cox, S R, additional, Hayward, C, additional, Porteous, D J, additional, Evans, J, additional, McIntosh, A M, additional, Gallacher, J, additional, Craddock, N, additional, Pell, J P, additional, Smith, D J, additional, Gale, C R, additional, and Deary, I J, additional
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- 2016
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40. Genetic contributions to variation in general cognitive function : a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
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Davies, G., Armstrong, N., Bis, J. C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C. A., Kirin, M., Lahti, J., van der Lee, S. J., Le Hellard, S., Liu, T., Marioni, R. E., Oldmeadow, C., Postmus, I., Smith, A. V., Smith, J. A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S. E., Hill, W. D., Liewald, D. C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A. A., Au, R., Becker, J. T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B. M., Campbell, H., Corley, J., De Jager, P. L., Dufouil, C., Eriksson, J. G., Espeseth, T., Faul, J. D., Ford, I., Gottesman, R. F., Griswold, M. E., Gudnason, V., Harris, T. B., Heiss, G., Hofman, A., Holliday, E. G., Huffman, J., Kardia, S. L. R., Kochan, N., Knopman, D. S., Kwok, J. B., Lambert, J-C, Lee, T., Li, G., Li, S-C, Loitfelder, M., Lopez, O. L., Lundervold, A. J., Lundquist, Anders, Mather, K. A., Mirza, S. S., Nyberg, Lars, Oostra, B. A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B. M., Redmond, P., Reppermund, S., Rotter, J. I., Schmidt, H., Schuur, M., Schofield, P. W., Scott, R. J., Steen, V. M., Stott, D. J., Van Swieten, J. C., Taylor, K. D., Trollor, J., Trompet, S., Uitterlinden, A. G., Weinstein, G., Widen, E., Windham, B. G., Jukema, J. W., Wright, A. F., Wright, M. J., Yang, Q., Amieva, H., Attia, J. R., Bennett, D. A., Brodaty, H., de Craen, A. J. M., Hayward, C., Ikram, M. A., Lindenberger, U., Nilsson, Lars-Göran, Porteous, D. J., Raikkonen, K., Reinvang, I., Rudan, I., Sachdev, P. S., Schmidt, R., Schofield, P. R., Srikanth, V., Starr, J. M., Turner, S. T., Weir, D. R., Wilson, J. F., Van Duijn, C., Launer, L., Fitzpatrick, A. L., Seshadri, S., Jr, T. H. Mosley, Deary, I. J., Davies, G., Armstrong, N., Bis, J. C., Bressler, J., Chouraki, V., Giddaluru, S., Hofer, E., Ibrahim-Verbaas, C. A., Kirin, M., Lahti, J., van der Lee, S. J., Le Hellard, S., Liu, T., Marioni, R. E., Oldmeadow, C., Postmus, I., Smith, A. V., Smith, J. A., Thalamuthu, A., Thomson, R., Vitart, V., Wang, J., Yu, L., Zgaga, L., Zhao, W., Boxall, R., Harris, S. E., Hill, W. D., Liewald, D. C., Luciano, M., Adams, H., Ames, D., Amin, N., Amouyel, P., Assareh, A. A., Au, R., Becker, J. T., Beiser, A., Berr, C., Bertram, L., Boerwinkle, E., Buckley, B. M., Campbell, H., Corley, J., De Jager, P. L., Dufouil, C., Eriksson, J. G., Espeseth, T., Faul, J. D., Ford, I., Gottesman, R. F., Griswold, M. E., Gudnason, V., Harris, T. B., Heiss, G., Hofman, A., Holliday, E. G., Huffman, J., Kardia, S. L. R., Kochan, N., Knopman, D. S., Kwok, J. B., Lambert, J-C, Lee, T., Li, G., Li, S-C, Loitfelder, M., Lopez, O. L., Lundervold, A. J., Lundquist, Anders, Mather, K. A., Mirza, S. S., Nyberg, Lars, Oostra, B. A., Palotie, A., Papenberg, G., Pattie, A., Petrovic, K., Polasek, O., Psaty, B. M., Redmond, P., Reppermund, S., Rotter, J. I., Schmidt, H., Schuur, M., Schofield, P. W., Scott, R. J., Steen, V. M., Stott, D. J., Van Swieten, J. C., Taylor, K. D., Trollor, J., Trompet, S., Uitterlinden, A. G., Weinstein, G., Widen, E., Windham, B. G., Jukema, J. W., Wright, A. F., Wright, M. J., Yang, Q., Amieva, H., Attia, J. R., Bennett, D. A., Brodaty, H., de Craen, A. J. M., Hayward, C., Ikram, M. A., Lindenberger, U., Nilsson, Lars-Göran, Porteous, D. J., Raikkonen, K., Reinvang, I., Rudan, I., Sachdev, P. S., Schmidt, R., Schofield, P. R., Srikanth, V., Starr, J. M., Turner, S. T., Weir, D. R., Wilson, J. F., Van Duijn, C., Launer, L., Fitzpatrick, A. L., Seshadri, S., Jr, T. H. Mosley, and Deary, I. J.
- Abstract
General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
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- 2015
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41. Brain age predicts mortality
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Cole, J H, Ritchie, S J, Bastin, M E, Valdés Hernández, M C, Muñoz Maniega, S, Royle, N, Corley, J, Pattie, A, Harris, S E, Zhang, Q, Wray, N R, Redmond, P, Marioni, R E, Starr, J M, Cox, S R, Wardlaw, J M, Sharp, D J, and Deary, I J
- Abstract
Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, ‘brain-predicted age’, derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death.
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- 2018
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42. Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins
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Hill, W D, primary, Davies, G, additional, van de Lagemaat, L N, additional, Christoforou, A, additional, Marioni, R E, additional, Fernandes, C P D, additional, Liewald, D C, additional, Croning, M D R, additional, Payton, A, additional, Craig, L C A, additional, Whalley, L J, additional, Horan, M, additional, Ollier, W, additional, Hansell, N K, additional, Wright, M J, additional, Martin, N G, additional, Montgomery, G W, additional, Steen, V M, additional, Le Hellard, S, additional, Espeseth, T, additional, Lundervold, A J, additional, Reinvang, I, additional, Starr, J M, additional, Pendleton, N, additional, Grant, S G N, additional, Bates, T C, additional, and Deary, I J, additional
- Published
- 2014
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43. [Coronary vasomotor response to acetylcholine correlates with plasma levels of cyclosporin and triglycerides in patients with heart transplantation]
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Stefano Ghio, Campana C, Gavazzi A, De Servi S, Angoli L, Marioni R, Eleuteri E, Montemartini C, and Specchia G
- Subjects
Adult ,Postoperative Care ,Time Factors ,Coronary Disease ,Arteries ,Middle Aged ,Coronary Angiography ,Prognosis ,Coronary Vessels ,Acetylcholine ,Postoperative Complications ,Vasoconstriction ,Cyclosporine ,Heart Transplantation ,Humans ,Endothelium, Vascular ,Triglycerides - Abstract
Vasoconstriction of normal coronary arteries has been reported after intracoronary (i.c.) administration of acetylcholine (Ach) in cardiac transplant patients and has been related to early endothelial disfunction; the clinical correlates of this response are still unknown.We infused graded i.c. concentrations of Ach in 32 pts with angiographically smooth coronary arteries 1 to 3 years after heart transplantation. Changes in diameters of the proximal and middle segments of the left anterior descending coronary artery were measured by quantitative coronary angiography (automatic edge detection).The response to Ach ranged from +44% to -58%; at linear regression analysis it was significantly related to the plasma levels of cyclosporine (r = -0.39, p.05) and triglycerides (r = -0.42, p.02) but not to vessel diameter, recipient and donor age, time after transplantation, hypertension, cholesterol levels, number of acute rejection episodes and previous cytomegalovirus infections.In heart transplant pts with angiographically normal coronary arteries i.c. Ach may reveal endothelial disfunction which is associated with high cyclosporine and triglycerides plasma levels. Whether this response may predict an earlier development of coronary disease remains to be elucidated.
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- 1994
44. Blood rheology and cognition in the Edinburgh Type 2 Diabetes Study
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Marioni, R. E., primary, Deary, I. J., additional, Strachan, M. W., additional, Lowe, G. D., additional, Rumley, A., additional, Murray, G. D., additional, and Price, J. F., additional
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- 2010
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45. Variation in the uric acid transporter gene (SLC2A9) and memory performance
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Houlihan, L. M., primary, Wyatt, N. D., additional, Harris, S. E., additional, Hayward, C., additional, Gow, A. J., additional, Marioni, R. E., additional, Strachan, M. W. J., additional, Price, J. F., additional, Starr, J. M., additional, Wright, A. F., additional, and Deary, I. J., additional
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- 2010
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46. Age-associated cognitive decline
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Deary, I. J., primary, Corley, J., additional, Gow, A. J., additional, Harris, S. E., additional, Houlihan, L. M., additional, Marioni, R. E., additional, Penke, L., additional, Rafnsson, S. B., additional, and Starr, J. M., additional
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- 2009
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47. [Coronary disease of transplanted heart: prevalence, angiographic and etiopathogenetic aspects]
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Campana C, Gavazzi A, Marioni R, Angoli L, Graziano G, Veritti U, Eloisa Arbustini, Martinelli L, Viganò M, and Specchia G
- Subjects
Adult ,Male ,Electrocardiography ,Time Factors ,Risk Factors ,Heart Transplantation ,Humans ,Coronary Disease ,Female ,Middle Aged ,Coronary Angiography ,Echocardiography, Doppler - Abstract
Progressive coronary artery disease is the most important factor influencing late mortality after heart transplantation. The aim of the study was to evaluate prevalence and clinical and angiographic findings of accelerated atherosclerosis in cardiac transplanted patients. During the first 5 years of the Heart Transplant Clinical Program at Policlinico S Matteo, Pavia, 81 patients underwent 156 coronary angiographies. The immunosuppressive therapy was based on cyclosporine, azathioprine and steroids; in some patients a reduced immunosuppressive schedule was started because of the presence of adverse effects. Coronary angiographies were performed in 68 patients after 1 year, in 40 patients after 2 years, in 19 patients after 3 years and in 18 patients after 4 years. The presence of coronary artery disease was defined by the angiographic occurrence of any decrease in the luminal diameter (including minor irregularities): according to these criteria coronary artery disease was found in 29 angiographies, performed in 13 patients, with a prevalence of 16% (13/81). An evaluation of the annual incidence showed respectively 14.7% at 1 year, 22.5% at 2 years, 31.5% at 3 years, 22.2% at 4 years. Coronary artery disease involvement was predominantly monovascular (56%) after 1 year and with a multivessel expression in the following years (2-vessel disease 33%, 3-vessel disease 50%). The major clinical problems in the transplanted patients with coronary artery disease were 3 deaths, related with heart failure in 2 cases and with sudden death in 1 case, and a new transplantation procedure in 2 patients. Prevalence and incidence of coronary artery disease observed after heart transplantation in this population were similar to those reported by other Authors.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1991
48. Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia
- Author
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Hagenaars, S P, Harris, S E, Davies, G, Hill, W D, Liewald, D C M, Ritchie, S J, Marioni, R E, Fawns-Ritchie, C, Cullen, B, Malik, R, Worrall, B B, Sudlow, C L M, Wardlaw, J M, Gallacher, J, Pell, J, McIntosh, A M, Smith, D J, Gale, C R, and Deary, I J
- Abstract
Causes of the well-documented association between low levels of cognitive functioning and many adverse neuropsychiatric outcomes, poorer physical health and earlier death remain unknown. We used linkage disequilibrium regression and polygenic profile scoring to test for shared genetic aetiology between cognitive functions and neuropsychiatric disorders and physical health. Using information provided by many published genome-wide association study consortia, we created polygenic profile scores for 24 vascular–metabolic, neuropsychiatric, physiological–anthropometric and cognitive traits in the participants of UK Biobank, a very large population-based sample (N=112 151). Pleiotropy between cognitive and health traits was quantified by deriving genetic correlations using summary genome-wide association study statistics and to the method of linkage disequilibrium score regression. Substantial and significant genetic correlations were observed between cognitive test scores in the UK Biobank sample and many of the mental and physical health-related traits and disorders assessed here. In addition, highly significant associations were observed between the cognitive test scores in the UK Biobank sample and many polygenic profile scores, including coronary artery disease, stroke, Alzheimer’s disease, schizophrenia, autism, major depressive disorder, body mass index, intracranial volume, infant head circumference and childhood cognitive ability. Where disease diagnosis was available for UK Biobank participants, we were able to show that these results were not confounded by those who had the relevant disease. These findings indicate that a substantial level of pleiotropy exists between cognitive abilities and many human mental and physical health disorders and traits and that it can be used to predict phenotypic variance across samples.
- Published
- 2016
- Full Text
- View/download PDF
49. Assessing the genetic overlap between BMI and cognitive function
- Author
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Marioni, R E, Yang, J, Dykiert, D, Mõttus, R, Campbell, A, Davies, G, Hayward, C, Porteous, D J, Visscher, P M, and Deary, I J
- Abstract
Obesity and low cognitive function are associated with multiple adverse health outcomes across the life course. They have a small phenotypic correlation (r=−0.11; high body mass index (BMI)−low cognitive function), but whether they have a shared genetic aetiology is unknown. We investigated the phenotypic and genetic correlations between the traits using data from 6815 unrelated, genotyped members of Generation Scotland, an ethnically homogeneous cohort from five sites across Scotland. Genetic correlations were estimated using the following: same-sample bivariate genome-wide complex trait analysis (GCTA)–GREML; independent samples bivariate GCTA–GREML using Generation Scotland for cognitive data and four other samples (n=20 806) for BMI; and bivariate LDSC analysis using the largest genome-wide association study (GWAS) summary data on cognitive function (n=48 462) and BMI (n=339 224) to date. The GWAS summary data were also used to create polygenic scores for the two traits, with within- and cross-trait prediction taking place in the independent Generation Scotland cohort. A large genetic correlation of −0.51 (s.e. 0.15) was observed using the same-sample GCTA–GREML approach compared with −0.10 (s.e. 0.08) from the independent-samples GCTA–GREML approach and −0.22 (s.e. 0.03) from the bivariate LDSC analysis. A genetic profile score using cognition-specific genetic variants accounts for 0.08% (P=0.020) of the variance in BMI and a genetic profile score using BMI-specific variants accounts for 0.42% (P=1.9 × 10−7) of the variance in cognitive function. Seven common genetic variants are significantly associated with both traits at P<5 × 10−5, which is significantly more than expected by chance (P=0.007). All these results suggest there are shared genetic contributions to BMI and cognitive function.
- Published
- 2016
- Full Text
- View/download PDF
50. Incidence of sudden death (SD) in patients (PTS) with advanced congestive heart failure (ACHF) waiting for heart transplantation (HT)
- Author
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Campana, C., primary, Gavazzi, A., additional, Larizza, C., additional, Marioni, R., additional, Inserra, C., additional, Ponzetta, M., additional, and Montemartini, C., additional
- Published
- 1993
- Full Text
- View/download PDF
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