112 results on '"Hartmann, A.M."'
Search Results
2. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
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Blokland, G.A., Grove, J, Chen, C.Y., Cotsapas, C., Tobet, S., Handa, R., Clair, D. St, Lencz, T., Mowry, B.J., Periyasamy, S., Cairns, M.J., Tooney, P.A., Wu, J.Q., Kelly, B., Kirov, G., Sullivan, P.F., Corvin, A., Riley, B.P., Esko, T., Milani, L., Jönsson, E.G., Palotie, A., Ehrenreich, H., Begemann, M., Steixner-Kumar, A., Sham, P.C., Iwata, N., Weinberger, D.R., Gejman, P.V., Sanders, A.R., Buxbaum, J.D., Rujescu, D., Giegling, I., Konte, B., Hartmann, A.M., Bramon, E., Murray, R.M., Pato, M.T., Lee, J., Melle, I., Molden, E., Ophoff, R.A., McQuillin, A., Bass, N.J., Adolfsson, R., Malhotra, A.K., Martin, N.G., Fullerton, J.M., Mitchell, P.B., Schofield, P.R., Forstner, A.J., Degenhardt, F., Schaupp, S., Comes, A.L., Kogevinas, M., Guzman-Parra, J., Reif, A., Streit, F., Sirignano, L., Cichon, S., Grigoroiu-Serbanescu, M., Hauser, J., Lissowska, J., Mayoral, F., Müller-Myhsok, B., Świątkowska, B., Schulze, T.G., Nöthen, M.M., Rietschel, M., Kelsoe, J., Leboyer, M., Jamain, S., Etain, B., Bellivier, F., Vincent, J.B., Alda, M., O'Donovan, C., Cervantes, P., Biernacka, J.M., Frye, M., McElroy, S.L., Scott, L.J., Stahl, E.A., Landén, M., Hamshere, M.L., Smeland, O.B., Djurovic, S., Vaaler, A.E., Andreassen, O.A., Baune, B.T., Air, T., Preisig, M., Uher, R., Levinson, D.F., Weissman, M.M., Potash, J.B., Shi, J., Knowles, J.A., Bralten, J.B., Perlis, R.H., Lucae, S., Blokland, G.A., Grove, J, Chen, C.Y., Cotsapas, C., Tobet, S., Handa, R., Clair, D. St, Lencz, T., Mowry, B.J., Periyasamy, S., Cairns, M.J., Tooney, P.A., Wu, J.Q., Kelly, B., Kirov, G., Sullivan, P.F., Corvin, A., Riley, B.P., Esko, T., Milani, L., Jönsson, E.G., Palotie, A., Ehrenreich, H., Begemann, M., Steixner-Kumar, A., Sham, P.C., Iwata, N., Weinberger, D.R., Gejman, P.V., Sanders, A.R., Buxbaum, J.D., Rujescu, D., Giegling, I., Konte, B., Hartmann, A.M., Bramon, E., Murray, R.M., Pato, M.T., Lee, J., Melle, I., Molden, E., Ophoff, R.A., McQuillin, A., Bass, N.J., Adolfsson, R., Malhotra, A.K., Martin, N.G., Fullerton, J.M., Mitchell, P.B., Schofield, P.R., Forstner, A.J., Degenhardt, F., Schaupp, S., Comes, A.L., Kogevinas, M., Guzman-Parra, J., Reif, A., Streit, F., Sirignano, L., Cichon, S., Grigoroiu-Serbanescu, M., Hauser, J., Lissowska, J., Mayoral, F., Müller-Myhsok, B., Świątkowska, B., Schulze, T.G., Nöthen, M.M., Rietschel, M., Kelsoe, J., Leboyer, M., Jamain, S., Etain, B., Bellivier, F., Vincent, J.B., Alda, M., O'Donovan, C., Cervantes, P., Biernacka, J.M., Frye, M., McElroy, S.L., Scott, L.J., Stahl, E.A., Landén, M., Hamshere, M.L., Smeland, O.B., Djurovic, S., Vaaler, A.E., Andreassen, O.A., Baune, B.T., Air, T., Preisig, M., Uher, R., Levinson, D.F., Weissman, M.M., Potash, J.B., Shi, J., Knowles, J.A., Bralten, J.B., Perlis, R.H., and Lucae, S.
- Abstract
Item does not contain fulltext, BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and
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- 2022
3. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis
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Tielbeek, J.J., Uffelmann, E., Williams, B.S., Colodro-Conde, L., Gagnon, É., Mallard, T.T., Levitt, B.E., Jansen, P.R., Johansson, A, Sallis, H.M., Pistis, G., Saunders, G.R.B., Allegrini, A.G., Rimfeld, K., Konte, B., Klein, M., Hartmann, A.M., Salvatore, J.E., Nolte, I.M., Demontis, D., Malmberg, A.L.K., Burt, S.A., Savage, J.E., Sugden, K., Poulton, R., Harris, K.M., Vrieze, S., McGue, M., Iacono, W.G., Roth Mota, N., Mill, J., Viana, J.F., Mitchell, B.L., Morosoli, J.J., Andlauer, T.F.M., Ouellet-Morin, I., Tremblay, R.E., Côté, S.M., Gouin, J.-P., Brendgen, M.R., Dionne, G., Vitaro, F., Lupton, M.K., Martin, N.G., Porjesz, B., Hesselbrock, V., Foroud, T., Agrawal, A., Edenberg, H.J., Liu, Y, Plawecki, M.H., Kuperman, S., Kramer, J.R., Meyers, J.M., Kamarajan, C., Pandey, A., Bierut, L., Rice, J., Bucholz, K.K., Schuckit, M.A., Tischfield, J., Hart, R., Almasy, L., Goate, A., Slesinger, P., Scott, D., Castelao, E., Räikkönen, K., Eriksson, J.G., Lahti, J., Hartman, C.A, Oldehinkel, A.J., Snieder, H., Liu, H., Preisig, M., Whipp, A., Vuoksimaa, E., Lu, Y., Jern, P., Rujescu, D., Giegling, I., Palviainen, T., Kaprio, J., Harden, K.P., Munafò, M.R., Morneau-Vaillancourt, G., Plomin, R., Viding, E., Boutwell, B.B., Aliev, F., Dick, D.M., Popma, A., Faraone, S.V, Børglum, A.D., Medland, S.E., Franke, B., Boivin, M., Pingault, J.-B., Glennon, J.C., Barnes, J.C., Fisher, S.E., Tielbeek, J.J., Uffelmann, E., Williams, B.S., Colodro-Conde, L., Gagnon, É., Mallard, T.T., Levitt, B.E., Jansen, P.R., Johansson, A, Sallis, H.M., Pistis, G., Saunders, G.R.B., Allegrini, A.G., Rimfeld, K., Konte, B., Klein, M., Hartmann, A.M., Salvatore, J.E., Nolte, I.M., Demontis, D., Malmberg, A.L.K., Burt, S.A., Savage, J.E., Sugden, K., Poulton, R., Harris, K.M., Vrieze, S., McGue, M., Iacono, W.G., Roth Mota, N., Mill, J., Viana, J.F., Mitchell, B.L., Morosoli, J.J., Andlauer, T.F.M., Ouellet-Morin, I., Tremblay, R.E., Côté, S.M., Gouin, J.-P., Brendgen, M.R., Dionne, G., Vitaro, F., Lupton, M.K., Martin, N.G., Porjesz, B., Hesselbrock, V., Foroud, T., Agrawal, A., Edenberg, H.J., Liu, Y, Plawecki, M.H., Kuperman, S., Kramer, J.R., Meyers, J.M., Kamarajan, C., Pandey, A., Bierut, L., Rice, J., Bucholz, K.K., Schuckit, M.A., Tischfield, J., Hart, R., Almasy, L., Goate, A., Slesinger, P., Scott, D., Castelao, E., Räikkönen, K., Eriksson, J.G., Lahti, J., Hartman, C.A, Oldehinkel, A.J., Snieder, H., Liu, H., Preisig, M., Whipp, A., Vuoksimaa, E., Lu, Y., Jern, P., Rujescu, D., Giegling, I., Palviainen, T., Kaprio, J., Harden, K.P., Munafò, M.R., Morneau-Vaillancourt, G., Plomin, R., Viding, E., Boutwell, B.B., Aliev, F., Dick, D.M., Popma, A., Faraone, S.V, Børglum, A.D., Medland, S.E., Franke, B., Boivin, M., Pingault, J.-B., Glennon, J.C., Barnes, J.C., and Fisher, S.E.
- Abstract
Item does not contain fulltext
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- 2022
4. 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., Jr 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. 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. 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.M. Ruiz, A. Ramirez, A. Lambert, J.-C. EADB GR@ACE DEGESCO EADI GERAD Demgene FinnGen ADGC CHARGE
- Abstract
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. © 2022. The Author(s).
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- 2022
5. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
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de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. Popp, J. Deckert, J. Buerger, K. Morgan, K. Fließbach, K. Sleegers, K. Molina-Porcel, L. Kilander, L. Weinhold, L. Farrer, L.A. Wang, L.-S. Kleineidam, L. Farotti, L. Parnetti, L. Tremolizzo, L. Hausner, L. Benussi, L. Froelich, L. Ikram, M.A. Deniz-Naranjo, M.C. Tsolaki, M. Rosende-Roca, M. Löwenmark, M. Hulsman, M. Spallazzi, M. Pericak-Vance, M.A. Esiri, M. Bernal Sánchez-Arjona, M. Dalmasso, M.C. Martínez-Larrad, M.T. Arcaro, M. Nöthen, M.M. Fernández-Fuertes, M. Dichgans, M. Ingelsson, M. Herrmann, M.J. Scherer, M. Vyhnalek, M. Kosmidis, M.H. Yannakoulia, M. Schmid, M. Ewers, M. Heneka, M.T. Wagner, M. Scamosci, M. Kivipelto, M. Hiltunen, M. Zulaica, M. Alegret, M. Fornage, M. Roberto, N. van Schoor, N.M. Seidu, N.M. Banaj, N. Armstrong, N.J. Scarmeas, N. Scherbaum, N. Goldhardt, O. Hanon, O. Peters, O. Skrobot, O.A. Quenez, O. Lerch, O. Bossù, P. Caffarra, P. Dionigi Rossi, P. Sakka, P. Hoffmann, P. Holmans, P.A. Fischer, P. Riederer, P. Yang, Q. Marshall, R. Kalaria, R.N. Mayeux, R. Vandenberghe, R. Cecchetti, R. Ghidoni, R. Frikke-Schmidt, R. Sorbi, S. Hägg, S. Engelborghs, S. Helisalmi, S. Botne Sando, S. Kern, S. Archetti, S. Boschi, S. Fostinelli, S. Gil, S. Mendoza, S. Mead, S. Ciccone, S. Djurovic, S. Heilmann-Heimbach, S. Riedel-Heller, S. Kuulasmaa, T. del Ser, T. Lebouvier, T. Polak, T. Ngandu, T. Grimmer, T. Bessi, V. Escott-Price, V. Giedraitis, V. Deramecourt, V. Maier, W. Jian, X. Pijnenburg, Y.A.L. Smith, A.D. Saenz, A. Bizzarro, A. Lauria, A. Vacca, A. Solomon, A. Anastasiou, A. Richardson, A. Boland, A. Koivisto, A. Daniele, A. Greco, A. Marianthi, A. McGuinness, B. Fin, B. Ferrari, C. Custodero, C. Ferrarese, C. Ingino, C. Mangone, C. Reyes Toso, C. Martínez, C. Cuesta, C. Muchnik, C. Joachim, C. Ortiz, C. Besse, C. Johansson, C. Zoia, C.P. Laske, C. Anastasiou, C. Palacio, D.L. Politis, D.G. Janowitz, D. Craig, D. Mann, D.M. Neary, D. Jürgen, D. Daian, D. Belezhanska, D. Kohler, E. Castaño, E.M. Koutsouraki, E. Chipi, E. De Roeck, E. Costantini, E. Vardy, E.R.L.C. Piras, F. Roveta, F. Piras, F. Prestia, F.A. Assogna, F. Salani, F. Sala, G. Lacidogna, G. Novack, G. Wilcock, G. Thonberg, H. Kölsch, H. Weber, H. Boecker, H. Etchepareborda, I. Piaceri, I. Tuomilehto, J. Lindström, J. Laczo, J. Johnston, J. Deleuze, J.-F. Harris, J. Schott, J.M. Priller, J. Bacha, J.I. Snowden, J. Lisso, J. Mihova, K.Y. Traykov, L. Morelli, L. Brusco, L.I. Rainer, M. Takalo, M. Bjerke, M. Del Zompo, M. Serpente, M. Sanchez Abalos, M. Rios, M. Peltonen, M. Herrman, M.J. Kosmidis, M.H. Kohler, M. Rojo, M. Jones, M. Orsini, M. Medel, N. Olivar, N. Fox, N.C. Salvadori, N. Hooper, N.M. Galeano, P. Solis, P. Bastiani, P. Mecocci, P. Passmore, P. Heun, R. Antikainen, R. Olaso, R. Perneczky, R. Germani, S. López-García, S. Love, S. Mehrabian, S. Bagnoli, S. Kochen, S. Andreoni, S. Teipel, S. Todd, S. Pickering-Brown, S. Natunen, T. Tegos, T. Laatikainen, T. Strandberg, T. Polvikoski, T.M. Matoska, V. Ciullo, V. Cores, V. Solfrizzi, V. Lisetti, V. Sevillano, Z. Abdelnour, C. Aguilera, N. Alarcon, E. Alegret, M. Benaque, A. Boada, M. Buendia, M. Cañabate, P. Carracedo, A. Corbatón-Anchuelo, A. Diego, S. Espinosa, A. Gailhajenet, A. Gil, S. Guitart, M. Hernández, I. Ibarria, M. Lafuente, A. Macias, J. Maroñas, O. Martín, E. Martínez, M.T. Marquié, M. Mauleón, A. Montrreal, L. Moreno-Grau, S. Moreno, M. Orellana, A. Ortega, G. Pancho, A. Pelejá, E. Pérez-Cordon, A. Pineda, J.A. Preckler, S. Quintela, I. Real, L.M. Rosende-Roca, M. Ruiz, A. Sáez, M.E. Sanabria, A. Serrano-Rios, M. Sotolongo-Grau, O. Tárraga, L. Valero, S. Vargas, L. Adarmes-Gómez, A.D. Alarcón-Martín, E. Alonso, M.D. Álvarez, I. Álvarez, V. Amer-Ferrer, G. Antequera, M. Antúnez, C. Baquero, M. Bernal, M. Blesa, R. Boada, M. Buiza-Rueda, D. Bullido, M.J. Burguera, J.A. Calero, M. Carrillo, F. Carrión-Claro, M. Casajeros, M.J. Clarimón, J. Cruz-Gamero, J.M. de Pancorbo, M.M. del Ser, T. Diez-Fairen, M. Escuela, R. Garrote-Espina, L. Fortea, J. Franco-Macías, E. Frank-García, A. García-Alberca, J.M. Garcia Madrona, S. Garcia-Ribas, G. Gómez-Garre, P. Hernández, I. Hevilla, S. Jesús, S. Labrador Espinosa, M.A. Lage, C. Legaz, A. Lleó, A. Lopez de Munain, A. López-García, S. Macias-García, D. Manzanares, S. Marín, M. Marín-Muñoz, J. Marín, T. Marquié, M. Martín Montes, A. Martínez, B. Martínez, C. Martínez, V. Martínez-Lage Álvarez, P. Medina, M. Mendioroz Iriarte, M. Mir, P. Molinuevo, J.L. Pastor, P. Pérez Tur, J. Periñán-Tocino, T. Pineda-Sanchez, R. Piñol-Ripoll, G. Rábano, A. Real de Asúa, D. Rodrigo, S. Rodríguez-Rodríguez, E. Royo, J.L. Ruiz, A. Sanchez del Valle Díaz, R. Sánchez-Juan, P. Sastre, I. Valero, S. Vicente, M.P. Vigo-Ortega, R. Vivancos, L. Macleod, C. McCracken, C. Brayne, C. Bresner, C. Grozeva, D. Bellou, E. Sommerville, E.W. Matthews, F. Leonenko, G. Menzies, G. Windle, G. Harwood, J. Phillips, J. Bennett, K. Luckuck, L. Clare, L. Woods, R. Saad, S. Burholt, V. Jansen, I.E. Rongve, A. Kehoe, P.G. Garcia-Ribas, G. Sánchez-Juan, P. Pastor, P. Pérez-Tur, J. Piñol-Ripoll, G. Lopez de Munain, A. García-Alberca, J.M. Bullido, M.J. Álvarez, V. Lleó, A. Real, L.M. Scheltens, P. Holstege, H. Marquié, M. Sáez, M.E. Carracedo, Á. Amouyel, P. Schellenberg, G.D. Williams, J. Seshadri, S. van Duijn, C.M. Mather, K.A. Sánchez-Valle, R. Serrano-Ríos, M. Orellana, A. Tárraga, L. Blennow, K. Huisman, M. Andreassen, O.A. Posthuma, D. Clarimón, J. Boada, M. van der Flier, W.M. Ramirez, A. Lambert, J.-C. van der Lee, S.J. Ruiz, A. EADB contributors The GR@ACE study group DEGESCO consortium IGAP (ADGC, CHARGE, EADI, GERAD) PGC-ALZ consortia
- Abstract
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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- 2021
6. Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics
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Lam, M. Chen, C.-Y. Ge, T. Xia, Y. Hill, D.W. Trampush, J.W. Yu, J. Knowles, E. Davies, G. Stahl, E.A. Huckins, L. Liewald, D.C. Djurovic, S. Melle, I. Christoforou, A. Reinvang, I. DeRosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Hartmann, A.M. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Koltai, D.C. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Smyrnis, N. Bilder, R.M. Freimer, N.B. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M.C. Andreassen, O.A. Deary, I.J. Glahn, D.C. Huang, H. Liu, C. Malhotra, A.K. Lencz, T.
- Abstract
Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing. © 2021, The Author(s).
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- 2021
7. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
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Munn-Chernoff, M.A. Johnson, E.C. Chou, Y.-L. Coleman, J.R.I. Thornton, L.M. Walters, R.K. Yilmaz, Z. Baker, J.H. Hübel, C. Gordon, S. Medland, S.E. Watson, H.J. Gaspar, H.A. Bryois, J. Hinney, A. Leppä, V.M. Mattheisen, M. Ripke, S. Yao, S. Giusti-Rodríguez, P. Hanscombe, K.B. Adan, R.A.H. Alfredsson, L. Ando, T. Andreassen, O.A. Berrettini, W.H. Boehm, I. Boni, C. Boraska Perica, V. Buehren, K. Burghardt, R. Cassina, M. Cichon, S. Clementi, M. Cone, R.D. Courtet, P. Crow, S. Crowley, J.J. Danner, U.N. Davis, O.S.P. de Zwaan, M. Dedoussis, G. Degortes, D. DeSocio, J.E. Dick, D.M. Dikeos, D. Dina, C. Dmitrzak-Weglarz, M. Docampo, E. Duncan, L.E. Egberts, K. Ehrlich, S. Escaramís, G. Esko, T. Estivill, X. Farmer, A. Favaro, A. Fernández-Aranda, F. Fichter, M.M. Fischer, K. Föcker, M. Foretova, L. Forstner, A.J. Forzan, M. Franklin, C.S. Gallinger, S. Giegling, I. Giuranna, J. Gonidakis, F. Gorwood, P. Gratacos Mayora, M. Guillaume, S. Guo, Y. Hakonarson, H. Hatzikotoulas, K. Hauser, J. Hebebrand, J. Helder, S.G. Herms, S. Herpertz-Dahlmann, B. Herzog, W. Huckins, L.M. Hudson, J.I. Imgart, H. Inoko, H. Janout, V. Jiménez-Murcia, S. Julià, A. Kalsi, G. Kaminská, D. Karhunen, L. Karwautz, A. Kas, M.J.H. Kennedy, J.L. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Klump, K.L. Knudsen, G.P.S. La Via, M.C. Le Hellard, S. Levitan, R.D. Li, D. Lilenfeld, L. Lin, B.D. Lissowska, J. Luykx, J. Magistretti, P.J. Maj, M. Mannik, K. Marsal, S. Marshall, C.R. Mattingsdal, M. McDevitt, S. McGuffin, P. Metspalu, A. Meulenbelt, I. Micali, N. Mitchell, K. Monteleone, A.M. Monteleone, P. Nacmias, B. Navratilova, M. Ntalla, I. O'Toole, J.K. Ophoff, R.A. Padyukov, L. Palotie, A. Pantel, J. Papezova, H. Pinto, D. Rabionet, R. Raevuori, A. Ramoz, N. Reichborn-Kjennerud, T. Ricca, V. Ripatti, S. Ritschel, F. Roberts, M. Rotondo, A. Rujescu, D. Rybakowski, F. Santonastaso, P. Scherag, A. Scherer, S.W. Schmidt, U. Schork, N.J. Schosser, A. Seitz, J. Slachtova, L. Slagboom, P.E. Slof-Op't Landt, M.C.T. Slopien, A. Sorbi, S. Świątkowska, B. Szatkiewicz, J.P. Tachmazidou, I. Tenconi, E. Tortorella, A. Tozzi, F. Treasure, J. Tsitsika, A. Tyszkiewicz-Nwafor, M. Tziouvas, K. van Elburg, A.A. van Furth, E.F. Wagner, G. Walton, E. Widen, E. Zeggini, E. Zerwas, S. Zipfel, S. Bergen, A.W. Boden, J.M. Brandt, H. Crawford, S. Halmi, K.A. Horwood, L.J. Johnson, C. Kaplan, A.S. Kaye, W.H. Mitchell, J. Olsen, C.M. Pearson, J.F. Pedersen, N.L. Strober, M. Werge, T. Whiteman, D.C. Woodside, D.B. Grove, J. Henders, A.K. Larsen, J.T. Parker, R. Petersen, L.V. Jordan, J. Kennedy, M.A. Birgegård, A. Lichtenstein, P. Norring, C. Landén, M. Mortensen, P.B. Polimanti, R. McClintick, J.N. Adkins, A.E. Aliev, F. Bacanu, S.-A. Batzler, A. Bertelsen, S. Biernacka, J.M. Bigdeli, T.B. Chen, L.-S. Clarke, T.-K. Degenhardt, F. Docherty, A.R. Edwards, A.C. Foo, J.C. Fox, L. Frank, J. Hack, L.M. Hartmann, A.M. Hartz, S.M. Heilmann-Heimbach, S. Hodgkinson, C. Hoffmann, P. Hottenga, J.-J. Konte, B. Lahti, J. Lahti-Pulkkinen, M. Lai, D. Ligthart, L. Loukola, A. Maher, B.S. Mbarek, H. McIntosh, A.M. McQueen, M.B. Meyers, J.L. Milaneschi, Y. Palviainen, T. Peterson, R.E. Ryu, E. Saccone, N.L. Salvatore, J.E. Sanchez-Roige, S. Schwandt, M. Sherva, R. Streit, F. Strohmaier, J. Thomas, N. Wang, J.-C. Webb, B.T. Wedow, R. Wetherill, L. Wills, A.G. Zhou, H. Boardman, J.D. Chen, D. Choi, D.-S. Copeland, W.E. Culverhouse, R.C. Dahmen, N. Degenhardt, L. Domingue, B.W. Frye, M.A. Gäebel, W. Hayward, C. Ising, M. Keyes, M. Kiefer, F. Koller, G. Kramer, J. Kuperman, S. Lucae, S. Lynskey, M.T. Maier, W. Mann, K. Männistö, S. Müller-Myhsok, B. Murray, A.D. Nurnberger, J.I. Preuss, U. Räikkönen, K. Reynolds, M.D. Ridinger, M. Scherbaum, N. Schuckit, M.A. Soyka, M. Treutlein, J. Witt, S.H. Wodarz, N. Zill, P. Adkins, D.E. Boomsma, D.I. Bierut, L.J. Brown, S.A. Bucholz, K.K. Costello, E.J. de Wit, H. Diazgranados, N. Eriksson, J.G. Farrer, L.A. Foroud, T.M. Gillespie, N.A. Goate, A.M. Goldman, D. Grucza, R.A. Hancock, D.B. Harris, K.M. Hesselbrock, V. Hewitt, J.K. Hopfer, C.J. Iacono, W.G. Johnson, E.O. Karpyak, V.M. Kendler, K.S. Kranzler, H.R. Krauter, K. Lind, P.A. McGue, M. MacKillop, J. Madden, P.A.F. Maes, H.H. Magnusson, P.K.E. Nelson, E.C. Nöthen, M.M. Palmer, A.A. Penninx, B.W.J.H. Porjesz, B. Rice, J.P. Rietschel, M. Riley, B.P. Rose, R.J. Shen, P.-H. Silberg, J. Stallings, M.C. Tarter, R.E. Vanyukov, M.M. Vrieze, S. Wall, T.L. Whitfield, J.B. Zhao, H. Neale, B.M. Wade, T.D. Heath, A.C. Montgomery, G.W. Martin, N.G. Sullivan, P.F. Kaprio, J. Breen, G. Gelernter, J. Edenberg, H.J. Bulik, C.M. Agrawal, A.
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mental disorders - Abstract
Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = −0.19 to −0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors. © 2020 Society for the Study of Addiction
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- 2021
8. Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease
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Traschütz, A., Cortese, A., Reich, S., Dominik, N., Faber, J., Jacobi, H., Hartmann, A.M., Rujescu, D., Montaut, S., Echaniz-Laguna, A., Erer, S., Schütz, V.C., Tarnutzer, A.A., Sturm, M., Haack, T.B., Vaucamps-Diedhiou, N., Puccio, H., Schöls, L., Klockgether, T., Warrenburg, B.P.C. van de, Paucar, M., Timmann, D., Hilgers, R.D., Gazulla, J., Strupp, M., Moris, G., Filla, A., Houlden, H., Anheim, M., Infante, J., Basak, A.N., Synofzik, M., Traschütz, A., Cortese, A., Reich, S., Dominik, N., Faber, J., Jacobi, H., Hartmann, A.M., Rujescu, D., Montaut, S., Echaniz-Laguna, A., Erer, S., Schütz, V.C., Tarnutzer, A.A., Sturm, M., Haack, T.B., Vaucamps-Diedhiou, N., Puccio, H., Schöls, L., Klockgether, T., Warrenburg, B.P.C. van de, Paucar, M., Timmann, D., Hilgers, R.D., Gazulla, J., Strupp, M., Moris, G., Filla, A., Houlden, H., Anheim, M., Infante, J., Basak, A.N., and Synofzik, M.
- Abstract
Item does not contain fulltext, OBJECTIVE: To delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). METHODS: Multimodal RFC1 repeat screening (PCR, Southern blot, whole-exome/genome sequencing-based approaches) combined with cross-sectional and longitudinal deep phenotyping in (1) cross-European cohort A (70 families) with ≥2 features of CANVAS or ataxia with chronic cough (ACC) and (2) Turkish cohort B (105 families) with unselected late-onset ataxia. RESULTS: Prevalence of RFC1 disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1 disease was also identified in Western and Eastern Asian individuals and even by whole-exome sequencing. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea or dystonia (11%). Ataxia progression was ≈1.3 Scale for the Assessment and Rating of Ataxia points per year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1 years]) but also included early falls, variable nonlinear phases of MSA-C-like progression (SARA points 2.5-5.5 per year), and premature death. Treatment trials require 330 (1-year trial) and 132 (2-year trial) patients in total to detect 50% reduced progression. CONCLUSIONS: RFC1 disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our na
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- 2021
9. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
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de Rojas, I., Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I.E., Pedersen, N.L., Stringa, N., Zettergren, A., Hernández, I., Montrreal, L., Antúnez, C., Antonell, A., Tankard, R.M., Bis, J.C., Sims, R., Bellenguez, C., Quintela, I., González-Perez, A., Calero, M., Franco-Macías, E., Macías, J., Blesa, R., Cervera-Carles, L., Menéndez-González, M., Frank-García, A., Royo, J.L., Moreno, F., Huerto Vilas, R., Baquero, M., Diez-Fairen, M., Lage, C., García-Madrona, S., García-González, P., Alarcón-Martín, E., Valero, S., Sotolongo-Grau, O., Ullgren, A., Naj, A.C., Lemstra, A.W., Benaque, A., Pérez-Cordón, A., Benussi, A., Rábano, A., Padovani, A., Squassina, A., de Mendonça, A., Arias Pastor, A., Kok, A.A.L., Meggy, A., Pastor, A.B., Espinosa, A., Corma-Gómez, A., Martín Montes, A., Sanabria, Á., DeStefano, A.L., Schneider, A., Haapasalo, A., Kinhult Ståhlbom, A., Tybjærg-Hansen, A., Hartmann, A.M., Spottke, A., Corbatón-Anchuelo, A., Rongve, A., Borroni, B., Arosio, B., Nacmias, B., Nordestgaard, B.G., Kunkle, B.W., Charbonnier, C., Abdelnour, C., Masullo, C., Martínez Rodríguez, C., Muñoz-Fernandez, C., Dufouil, C., Graff, C., Ferreira, C.B., Chillotti, C., Reynolds, C.A., Fenoglio, C., Van Broeckhoven, C., Clark, C., Pisanu, C., Satizabal, C.L., Holmes, C., Buiza-Rueda, D., Aarsland, D., Rujescu, D., Alcolea, D., Galimberti, D., Wallon, D., Seripa, D., Grünblatt, E., Dardiotis, E., Düzel, E., Scarpini, E., Conti, E., Rubino, E., Gelpi, E., Rodriguez-Rodriguez, E., Duron, E., Boerwinkle, E., Ferri, E., Tagliavini, F., Küçükali, F., Pasquier, F., Sanchez-Garcia, F., Mangialasche, F., Jessen, F., Nicolas, G., Selbæk, G., Ortega, G., Chêne, G., Hadjigeorgiou, G., Rossi, G, Spalletta, G., Giaccone, G., Grande, G., Binetti, G., Papenberg, G., Hampel, H., Bailly, H., Zetterberg, H., Soininen, H., Karlsson, I.K., Alvarez, I., Appollonio, I., Giegling, I., Skoog, I., Saltvedt, I., Rainero, I., Rosas Allende, I., Hort, J., Diehl-Schmid, J., Van Dongen, J., Vidal, J-S, Lehtisalo, J., Wiltfang, J., Thomassen, J.Q., Kornhuber, J., Haines, J.L., Vogelgsang, J., Pineda, J.A., Fortea, J., Popp, J., Deckert, J., Buerger, K., Morgan, K., Fließbach, K., Sleegers, K., Molina-Porcel, L., Kilander, L., Weinhold, L., Farrer, L.A., Wang, L-S, Kleineidam, L., Farotti, L., Parnetti, L., Tremolizzo, L., Hausner, L., Benussi, L., Froelich, L., Ikram, M.A., Deniz-Naranjo, M.C., Tsolaki, M., Rosende-Roca, M., Löwenmark, M., Hulsman, M., Spallazzi, M., Pericak-Vance, M.A., Esiri, M., Bernal Sánchez-Arjona, M., Dalmasso, M.C., Martínez-Larrad, M.T., Arcaro, M., Nöthen, M.M., Fernández-Fuertes, M., Dichgans, M., Ingelsson, M., Herrmann, M.J., Scherer, M., Vyhnalek, M., Kosmidis, M.H., Yannakoulia, M., Schmid, M., Ewers, M., Heneka, M.T., Wagner, M., Scamosci, M., Kivipelto, M., Hiltunen, M., Zulaica, M., Alegret, M., Fornage, M., Roberto, N., van Schoor, N.M., Seidu, N.M., Banaj, N., Armstrong, N.J., Scarmeas, N., Scherbaum, N., Goldhardt, O., Hanon, O., Peters, O., Skrobot, O.A., Quenez, O., Lerch, O., Bossù, P., Caffarra, P., Dionigi Rossi, P., Sakka, P., Hoffmann, P., Holmans, P.A., Fischer, P., Riederer, P., Yang, Q., Marshall, R., Kalaria, R.N., Mayeux, R., Vandenberghe, R., Cecchetti, R., Ghidoni, R., Frikke-Schmidt, R., Sorbi, S., Hägg, S., Engelborghs, S., Helisalmi, S., Botne Sando, S., Kern, S., Archetti, S., Boschi, S., Fostinelli, S., Gil, S., Mendoza, S., Mead, S., Ciccone, S., Djurovic, S., Heilmann-Heimbach, S., Riedel-Heller, S., Kuulasmaa, T., del Ser, T., Lebouvier, T., Polak, T., Ngandu, T., Grimmer, T., Bessi, V., Escott-Price, V., Giedraitis, V., Deramecourt, V., Maier, W., Jian, X., Pijnenburg, Y.A.L., Smith, A.D., Saenz, A., Bizzarro, A., Lauria, A., Vacca, A., Solomon, A., Anastasiou, A., Richardson, A., Boland, A., Koivisto, A., Daniele, A., Greco, A., Marianthi, A., McGuinness, B., Fin, B., Ferrari, Ca., Custodero, C., Ferrarese, C., Ingino, C., Mangone, C., Reyes Toso, C., Martinez, C., Cuesta, C., Muchnik, C., Joachim, C., Ortiz, C., Besse, C., Johansson, C., Zoia, C.P., Laske, C., Anastasiou, C., Palacio, D.L., Politis, D.G., Janowitz, D., Craig, D., Mann, D.M., Neary, D., Jürgen, D., Daian, D., Belezhanska, D., Kohler, E., Castaño, E.M., Koutsouraki, E., Chipi, E., De Roeck, E., Costantini, E., Vardy, E.R.L.C., Piras, F., Roveta, F., Prestia, F.A., Assogna, F., Salani, F., Sala, G., Lacidogna, G., Novack, G., Wilcock, G., Thonberg, H., Kölsch, H., Weber, H., Boecker, H., Etchepareborda, I., Piaceri, I., Tuomilehto, J., Lindström, J., Laczo, J., Johnston, J., Deleuze, J-F, Harris, J., Schott, J.M., Priller, J., Bacha, J.I., Snowden, J., Lisso, J., Mihova, K.Y., Traykov, L., Morelli, L., Brusco, L.I., Rainer, M., Takalo, M., Bjerke, M., Del Zompo, M., Serpente, M., Sanchez Abalos, M., Rios, M., Peltonen, M., Herrman, M.J., Kohler, M., Rojo, M., Jones, M., Orsini, M., Medel, N., Olivar, N., Fox, N.C., Salvadori, N., Hooper, N.M., Galeano, P., Solis, P., Bastiani, P., Mecocci, P., Passmore, P., Heun, R., Antikainen, R., Olaso, R., Perneczky, R., Germani, S., López-García, S., Love, S., Mehrabian, S., Bagnoli, S., Kochen, S., Andreoni, S., Teipel, S., Todd, S., Pickering-Brown, S., Natunen, T., Tegos, T., Laatikainen, T., Strandberg, T., Polvikoski, T.M., Matoska, V., Ciullo, V., Cores, V., Solfrizzi, V., Lisetti, V., Sevillano, Z., Aguilera, N., Alarcon, E., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., Diego, S., Gailhajenet, A., Guitart, M., González-Pérez, A., Ibarria, M., Lafuente, A., Macias, J., Maroñas, O., Martín, E., Martínez, M. T., Marquié, M., Mauleón, A., Moreno, M., Orellana, A., Pancho, A., Pelejá, E., Pérez-Cordon, A., Pineda, J. A., Preckler, S., Real, L. M., Ruiz, A., Sáez, M. E., Sanabria, A., Serrano-Rios, M., Tárraga, L., Vargas, L., Adarmes-Gómez, A. D., Alonso, M. D., Álvarez, I., Álvarez, V., Amer-Ferrer, G., Antequera, M., Bernal, M., Bullido, M.J., Burguera, J.A., Carrillo, F., Carrión-Claro, M., Casajeros, M.J., Clarimón, J., Cruz-Gamero, J.M., de Pancorbo, M.M., Escuela, R., Garrote-Espina, L., García-Alberca, J.M., Garcia Madrona, S., Garcia-Ribas, G., Gómez-Garre, P., Hevilla, S., Jesús, S., Labrador Espinosa, M.A., Legaz, A., Lleó, A., Lopez de Munain, A., Macias-García, D., Manzanares, S., Marín, M., Marín-Muñoz, J., Marín, T., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Mir, P., Molinuevo, J.L., Pastor, P., Pérez Tur, J., Periñán-Tocino, T., Pineda-Sanchez, R., Piñol-Ripoll, G., Real de Asúa, D., Rodrigo, S., Rodríguez-Rodríguez, E., Sanchez del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Vicente, M.P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, C., Bresner, C., Grozeva, D., Bellou, E., Sommerville, E.W., Matthews, F., Leonenko, G., Menzies, G., Windle, G., Harwood, J., Phillips, J., Bennett, K., Luckuck, L., Clare, L., Woods, R., Saad, S., Burholt, V., Kehoe, P.G., Pérez-Tur, J., Real, L.M., Scheltens, P., Holstege, H., Sáez, M.E., Carracedo, Á., Amouyel, P., Schellenberg, G.D., Williams, J., Seshadri, S., van Duijn, C.M., Mather, K.A., Sánchez-Valle, R., Serrano-Ríos, M., Blennow, K., Huisman, M., Andreassen, O.A., Posthuma, D., van der Flier, W.M., Ramirez, A., Lambert, J-C, van der Lee, S.J., de Rojas, I., Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I.E., Pedersen, N.L., Stringa, N., Zettergren, A., Hernández, I., Montrreal, L., Antúnez, C., Antonell, A., Tankard, R.M., Bis, J.C., Sims, R., Bellenguez, C., Quintela, I., González-Perez, A., Calero, M., Franco-Macías, E., Macías, J., Blesa, R., Cervera-Carles, L., Menéndez-González, M., Frank-García, A., Royo, J.L., Moreno, F., Huerto Vilas, R., Baquero, M., Diez-Fairen, M., Lage, C., García-Madrona, S., García-González, P., Alarcón-Martín, E., Valero, S., Sotolongo-Grau, O., Ullgren, A., Naj, A.C., Lemstra, A.W., Benaque, A., Pérez-Cordón, A., Benussi, A., Rábano, A., Padovani, A., Squassina, A., de Mendonça, A., Arias Pastor, A., Kok, A.A.L., Meggy, A., Pastor, A.B., Espinosa, A., Corma-Gómez, A., Martín Montes, A., Sanabria, Á., DeStefano, A.L., Schneider, A., Haapasalo, A., Kinhult Ståhlbom, A., Tybjærg-Hansen, A., Hartmann, A.M., Spottke, A., Corbatón-Anchuelo, A., Rongve, A., Borroni, B., Arosio, B., Nacmias, B., Nordestgaard, B.G., Kunkle, B.W., Charbonnier, C., Abdelnour, C., Masullo, C., Martínez Rodríguez, C., Muñoz-Fernandez, C., Dufouil, C., Graff, C., Ferreira, C.B., Chillotti, C., Reynolds, C.A., Fenoglio, C., Van Broeckhoven, C., Clark, C., Pisanu, C., Satizabal, C.L., Holmes, C., Buiza-Rueda, D., Aarsland, D., Rujescu, D., Alcolea, D., Galimberti, D., Wallon, D., Seripa, D., Grünblatt, E., Dardiotis, E., Düzel, E., Scarpini, E., Conti, E., Rubino, E., Gelpi, E., Rodriguez-Rodriguez, E., Duron, E., Boerwinkle, E., Ferri, E., Tagliavini, F., Küçükali, F., Pasquier, F., Sanchez-Garcia, F., Mangialasche, F., Jessen, F., Nicolas, G., Selbæk, G., Ortega, G., Chêne, G., Hadjigeorgiou, G., Rossi, G, Spalletta, G., Giaccone, G., Grande, G., Binetti, G., Papenberg, G., Hampel, H., Bailly, H., Zetterberg, H., Soininen, H., Karlsson, I.K., Alvarez, I., Appollonio, I., Giegling, I., Skoog, I., Saltvedt, I., Rainero, I., Rosas Allende, I., Hort, J., Diehl-Schmid, J., Van Dongen, J., Vidal, J-S, Lehtisalo, J., Wiltfang, J., Thomassen, J.Q., Kornhuber, J., Haines, J.L., Vogelgsang, J., Pineda, J.A., Fortea, J., Popp, J., Deckert, J., Buerger, K., Morgan, K., Fließbach, K., Sleegers, K., Molina-Porcel, L., Kilander, L., Weinhold, L., Farrer, L.A., Wang, L-S, Kleineidam, L., Farotti, L., Parnetti, L., Tremolizzo, L., Hausner, L., Benussi, L., Froelich, L., Ikram, M.A., Deniz-Naranjo, M.C., Tsolaki, M., Rosende-Roca, M., Löwenmark, M., Hulsman, M., Spallazzi, M., Pericak-Vance, M.A., Esiri, M., Bernal Sánchez-Arjona, M., Dalmasso, M.C., Martínez-Larrad, M.T., Arcaro, M., Nöthen, M.M., Fernández-Fuertes, M., Dichgans, M., Ingelsson, M., Herrmann, M.J., Scherer, M., Vyhnalek, M., Kosmidis, M.H., Yannakoulia, M., Schmid, M., Ewers, M., Heneka, M.T., Wagner, M., Scamosci, M., Kivipelto, M., Hiltunen, M., Zulaica, M., Alegret, M., Fornage, M., Roberto, N., van Schoor, N.M., Seidu, N.M., Banaj, N., Armstrong, N.J., Scarmeas, N., Scherbaum, N., Goldhardt, O., Hanon, O., Peters, O., Skrobot, O.A., Quenez, O., Lerch, O., Bossù, P., Caffarra, P., Dionigi Rossi, P., Sakka, P., Hoffmann, P., Holmans, P.A., Fischer, P., Riederer, P., Yang, Q., Marshall, R., Kalaria, R.N., Mayeux, R., Vandenberghe, R., Cecchetti, R., Ghidoni, R., Frikke-Schmidt, R., Sorbi, S., Hägg, S., Engelborghs, S., Helisalmi, S., Botne Sando, S., Kern, S., Archetti, S., Boschi, S., Fostinelli, S., Gil, S., Mendoza, S., Mead, S., Ciccone, S., Djurovic, S., Heilmann-Heimbach, S., Riedel-Heller, S., Kuulasmaa, T., del Ser, T., Lebouvier, T., Polak, T., Ngandu, T., Grimmer, T., Bessi, V., Escott-Price, V., Giedraitis, V., Deramecourt, V., Maier, W., Jian, X., Pijnenburg, Y.A.L., Smith, A.D., Saenz, A., Bizzarro, A., Lauria, A., Vacca, A., Solomon, A., Anastasiou, A., Richardson, A., Boland, A., Koivisto, A., Daniele, A., Greco, A., Marianthi, A., McGuinness, B., Fin, B., Ferrari, Ca., Custodero, C., Ferrarese, C., Ingino, C., Mangone, C., Reyes Toso, C., Martinez, C., Cuesta, C., Muchnik, C., Joachim, C., Ortiz, C., Besse, C., Johansson, C., Zoia, C.P., Laske, C., Anastasiou, C., Palacio, D.L., Politis, D.G., Janowitz, D., Craig, D., Mann, D.M., Neary, D., Jürgen, D., Daian, D., Belezhanska, D., Kohler, E., Castaño, E.M., Koutsouraki, E., Chipi, E., De Roeck, E., Costantini, E., Vardy, E.R.L.C., Piras, F., Roveta, F., Prestia, F.A., Assogna, F., Salani, F., Sala, G., Lacidogna, G., Novack, G., Wilcock, G., Thonberg, H., Kölsch, H., Weber, H., Boecker, H., Etchepareborda, I., Piaceri, I., Tuomilehto, J., Lindström, J., Laczo, J., Johnston, J., Deleuze, J-F, Harris, J., Schott, J.M., Priller, J., Bacha, J.I., Snowden, J., Lisso, J., Mihova, K.Y., Traykov, L., Morelli, L., Brusco, L.I., Rainer, M., Takalo, M., Bjerke, M., Del Zompo, M., Serpente, M., Sanchez Abalos, M., Rios, M., Peltonen, M., Herrman, M.J., Kohler, M., Rojo, M., Jones, M., Orsini, M., Medel, N., Olivar, N., Fox, N.C., Salvadori, N., Hooper, N.M., Galeano, P., Solis, P., Bastiani, P., Mecocci, P., Passmore, P., Heun, R., Antikainen, R., Olaso, R., Perneczky, R., Germani, S., López-García, S., Love, S., Mehrabian, S., Bagnoli, S., Kochen, S., Andreoni, S., Teipel, S., Todd, S., Pickering-Brown, S., Natunen, T., Tegos, T., Laatikainen, T., Strandberg, T., Polvikoski, T.M., Matoska, V., Ciullo, V., Cores, V., Solfrizzi, V., Lisetti, V., Sevillano, Z., Aguilera, N., Alarcon, E., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., Diego, S., Gailhajenet, A., Guitart, M., González-Pérez, A., Ibarria, M., Lafuente, A., Macias, J., Maroñas, O., Martín, E., Martínez, M. T., Marquié, M., Mauleón, A., Moreno, M., Orellana, A., Pancho, A., Pelejá, E., Pérez-Cordon, A., Pineda, J. A., Preckler, S., Real, L. M., Ruiz, A., Sáez, M. E., Sanabria, A., Serrano-Rios, M., Tárraga, L., Vargas, L., Adarmes-Gómez, A. D., Alonso, M. D., Álvarez, I., Álvarez, V., Amer-Ferrer, G., Antequera, M., Bernal, M., Bullido, M.J., Burguera, J.A., Carrillo, F., Carrión-Claro, M., Casajeros, M.J., Clarimón, J., Cruz-Gamero, J.M., de Pancorbo, M.M., Escuela, R., Garrote-Espina, L., García-Alberca, J.M., Garcia Madrona, S., Garcia-Ribas, G., Gómez-Garre, P., Hevilla, S., Jesús, S., Labrador Espinosa, M.A., Legaz, A., Lleó, A., Lopez de Munain, A., Macias-García, D., Manzanares, S., Marín, M., Marín-Muñoz, J., Marín, T., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Mir, P., Molinuevo, J.L., Pastor, P., Pérez Tur, J., Periñán-Tocino, T., Pineda-Sanchez, R., Piñol-Ripoll, G., Real de Asúa, D., Rodrigo, S., Rodríguez-Rodríguez, E., Sanchez del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Vicente, M.P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, C., Bresner, C., Grozeva, D., Bellou, E., Sommerville, E.W., Matthews, F., Leonenko, G., Menzies, G., Windle, G., Harwood, J., Phillips, J., Bennett, K., Luckuck, L., Clare, L., Woods, R., Saad, S., Burholt, V., Kehoe, P.G., Pérez-Tur, J., Real, L.M., Scheltens, P., Holstege, H., Sáez, M.E., Carracedo, Á., Amouyel, P., Schellenberg, G.D., Williams, J., Seshadri, S., van Duijn, C.M., Mather, K.A., Sánchez-Valle, R., Serrano-Ríos, M., Blennow, K., Huisman, M., Andreassen, O.A., Posthuma, D., van der Flier, W.M., Ramirez, A., Lambert, J-C, and van der Lee, S.J.
- Abstract
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.
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- 2021
10. Natural history, phenotypic spectrum, and discriminative features of multisystemic RFC1-disease
- Author
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Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Traschütz, A.; Cortese, A.; Reich, S.; Dominik, N.; Faber, J.; Jacobi, H.; Hartmann, A.M.; Rujescu, D.; Montaut, S.; Echaniz-Laguna, A.; Erer, S.; Schütz, V. C.; Tarnutzer, A. A.; Sturm, M.; Haack, T. B.; Vaucamps-Diedhiou, N.; Puccio, H.; Schöls, L.; Klockgether, T.; van de Warrenburg, B. P.; Paucar, M.; Timmann, D.; Hilgers, R. D.; Gazulla, J.; Strupp, M.; Moris, G.; Filla, A.; Houlden, H.; Anheim, M.; Infante, J.; Synofzik, M.; RFC1 study group, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Traschütz, A.; Cortese, A.; Reich, S.; Dominik, N.; Faber, J.; Jacobi, H.; Hartmann, A.M.; Rujescu, D.; Montaut, S.; Echaniz-Laguna, A.; Erer, S.; Schütz, V. C.; Tarnutzer, A. A.; Sturm, M.; Haack, T. B.; Vaucamps-Diedhiou, N.; Puccio, H.; Schöls, L.; Klockgether, T.; van de Warrenburg, B. P.; Paucar, M.; Timmann, D.; Hilgers, R. D.; Gazulla, J.; Strupp, M.; Moris, G.; Filla, A.; Houlden, H.; Anheim, M.; Infante, J.; Synofzik, M.; RFC1 study group, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine
- Abstract
Objective: to delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Methods: multimodal RFC1 repeat screening (PCR, Southern blot, whole-exome/genome sequencing-based approaches) combined with cross-sectional and longitudinal deep phenotyping in (1) cross-European cohort A (70 families) with ≥2 features of CANVAS or ataxia with chronic cough (ACC) and (2) Turkish cohort B (105 families) with unselected late-onset ataxia. Results: prevalence of RFC1 disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1 disease was also identified in Western and Eastern Asian individuals and even by whole-exome sequencing. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea or dystonia (11%). Ataxia progression was ≈1.3 Scale for the Assessment and Rating of Ataxia points per year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1 years]) but also included early falls, variable nonlinear phases of MSA-C-like progression (SARA points 2.5-5.5 per year), and premature death. Treatment trials require 330 (1-year trial) and 132 (2-year trial) patients in total to detect 50% reduced progression. Conclusions: RFC1 disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our na, European Union (EU); Horizon 2020; Research and Innovation Program; BMBF; E-Rare-3 network; PREPARE; DFG; EJP-RD network; PROSPAX; Solve-RD; University of Tubingen Medical Faculty; Clinician Scientist Program; Medical Research Council; Fondazione CARIPLO; ZonMW; Hersenstichting; Gossweiler Foundation; uniQure; Radboud University Medical Centre; Suna and İnan Kıraç Foundation; Koç University School of Medicine
- Published
- 2021
11. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (vol 9, 2098, 2018)
- Author
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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., Lee, S.J. van der, Ware, E.B., Windham, B.G., Wright, M.J., Yang, J.Y., 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., Hellard, S. le, Lee, T., Lehtimaki, T., Li, S.C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., 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., Jager, P.L. de, Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hagg, 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., Raikkonen, 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., Duijn, C.M. van, Villringer, A., Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.
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- 2019
12. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (Nature Communications, (2018), 9, 1, (2098), 10.1038/s41467-018-04362-x)
- Author
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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, I. Kleineidam, L. Knopman, D.S. Kochan, N.A. Konte, B. Kwok, J.B. Le Hellard, S. Lee, T. Lehtimäki, 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. 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. Dan Rujescu 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.
- Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,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. © 2019, The Author(s).
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- 2019
13. Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways
- Author
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Lam, M. Hill, W.D. Trampush, J.W. Yu, J. Knowles, E. Davies, G. Stahl, E. Huckins, L. Liewald, D.C. Djurovic, S. Melle, I. Sundet, K. Christoforou, A. Reinvang, I. DeRosse, P. Lundervold, A.J. Steen, V.M. Espeseth, T. Räikkönen, K. Widen, E. Palotie, A. Eriksson, J.G. Giegling, I. Konte, B. Hartmann, A.M. Roussos, P. Giakoumaki, S. Burdick, K.E. Payton, A. Ollier, W. Chiba-Falek, O. Attix, D.K. Need, A.C. Cirulli, E.T. Voineskos, A.N. Stefanis, N.C. Avramopoulos, D. Hatzimanolis, A. Arking, D.E. Smyrnis, N. Bilder, R.M. Freimer, N.A. Cannon, T.D. London, E. Poldrack, R.A. Sabb, F.W. Congdon, E. Conley, E.D. Scult, M.A. Dickinson, D. Straub, R.E. Donohoe, G. Morris, D. Corvin, A. Gill, M. Hariri, A.R. Weinberger, D.R. Pendleton, N. Bitsios, P. Rujescu, D. Lahti, J. Le Hellard, S. Keller, M.C. Andreassen, O.A. Deary, I.J. Glahn, D.C. Malhotra, A.K. Lencz, T.
- Subjects
mental disorders - Abstract
Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected (“concordant”) direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive (“discordant”) relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10−8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms—early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways—that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness. © 2019
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- 2019
14. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- Author
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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, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., 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., 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, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Le Hellard, S., Lee, T., Lehtimäki, T., Li, S-C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., 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., Bressler, J., Lencz, T., and Deary, I.J.
- Abstract
These authors contributed equally: Gail Davies, Max Lam. These authors jointly supervised this work: Todd Lencz, Ian J. Deary.
- Published
- 2019
15. Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease
- Author
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Sims, R., van der Lee, S.J., Naj, A.C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B.W., Boland, A., Raybould, R., Bis, J.C., Martin, E.R., Grenier-Boley, B., Heilmann-Heimbach, S., Chouraki, V., Kuzma, A.B., Sleegers, K., Vronskaya, M., Ruiz, A., Graham, R.R., Olaso, R., Hoffmann, P., Grove, M.L., Vardarajan, B.N., Hiltunen, M., Nöthen, M.M., White, C.C., Hamilton-Nelson, K.L., Epelbaum, J., Maier, W., Choi, S.H., Beecham, G.W., Dulary, C., Herms, S., Smith, A.V., Funk, C.C., Derbois, Forstner, A.J., Ahmad, S., Li, H., Bacq, D., Harold, D., Satizabal, C.L., Valladares, O., Squassina, A., Thomas, R., Brody, J.A., Qu, L., Sánchez-Juan, P., Morgan, T., Wolters, F.J., Zhao, Y., Garcia, F.S., Denning, N., Fornage, M., Malamon, J., Naranjo, M.C.D., Majounie, E., Mosley, T.H., Dombroski, B., Wallon, D., Lupton, M.K., Dupuis, J., Whitehead, P., Fratiglioni, L., Medway, C., Jian, X., Mukherjee, S., Keller, L., Brown, K., Lin, H., Cantwell, L.B., Panza, F., McGuinness, B., Moreno-Grau, S., Burgess, J.D., Solfrizzi, V., Proitsi, P., Adams, H.H., Allen, M., Seripa, D., Pastor, P., Cupples, L.A., Price, N.D., Hannequin, D., Frank-García, A., Levy, D., Chakrabarty, P., Caffarra, P., Giegling, I., Beiser, A.S., Giedraitis, V., Hampel, H., Garcia, M.E., Wang, X., Lannfelt, L., Mecocci, P., Eiriksdottir, G., Crane, P.K., Pasquier, F., Boccardi, V., Henández, I., Barber, R.C., Scherer, M., Tarraga, L., Adams, P.M., Leber, M., Chen, Y., Albert, M.S., Riedel-Heller, S., Emilsson, V., Beekly, D., Braae, A., Schmidt, R., Blacker, D., Masullo, C., Schmidt, H., Doody, R.S., Spalletta, G., Longstreth, W.T., Jr., Fairchild, T.J., Bossù, P., Lopez, O.L., Frosch, M.P., Sacchinelli, E., Ghetti, B., Yang, Q., Huebinger, R.M., Jessen, F., Li, S., Kamboh, M.I., Morris, J., Sotolongo-Grau, O., Katz, M.J., Corcoran, C., Dunstan, M., Braddel, A., Thomas, C., Meggy, A., Marshall, R., Gerrish, A., Chapman, J., Aguilar, M., Taylor, S., Hill, M., Fairén, M.D., Hodges, A., Vellas, B., Soininen, H., Kloszewska, I., Daniilidou, M., Uphill, J., Patel, Y., Hughes, J.T., Lord, J., Turton, J., Hartmann, A.M., Cecchetti, R., Fenoglio, C., Serpente, M., Arcaro, M., Caltagirone, C., Orfei, M.D., Ciaramella, A., Pichler, S., Mayhaus, M., Gu, W., Lleó, A., Fortea, J., Blesa, R., Barber, I.S., Brookes, K., Cupidi, C., Maletta, R.G., Carrell, D., Sorbi, S., Moebus, S., Urbano, M., Pilotto, A., Kornhuber, J., Bosco, P., Todd, S., Craig, D., Johnston, J., Gill, M., Lawlor, B., Lynch, A., Fox, N.C., Hardy, J., Albin, R.L., Apostolova, L.G., Arnold, S.E., Asthana, S., Atwood, C.S., Baldwin, C.T., Barnes, L.L., Barral, S., Beach, T.G., Becker, J.T., Bigio, E.H., Bird, T.D., Boeve, B.F., Bowen, J.D., Boxer, A., Burke, J.R., Burns, J.M., Buxbaum, J.D., Cairns, N.J., Cao, C., Carlson, C.S., Carlsson, C.M., Carney, R.M., Carrasquillo, M.M., Carroll, S.L., Diaz, C.C., Chui, H.C., Clark, D.G., Cribbs, D.H., Crocco, E.A., DeCarli, C., Dick, M., Duara, R., Evans, D.A., Faber, K.M., Fallon, K.B., Fardo, D.W., Farlow, M.R., Ferris, S., Foroud, T.M., Galasko, D.R., Gearing, M., Geschwind, D.H., Gilbert, J.R., Graff-Radford, N.R., Green, R.C., Growdon, J.H., Hamilton, R.L., Harrell, L.E., Honig, L.S., Huentelman, M.J., Hulette, C.M., Hyman, B.T., Jarvik, G.P., Abner, E., Jin, L.W., Jun, G., Karydas, A., Kaye, J.A., Kim, R., Kowall, N.W., Kramer, J.H., LaFerla, F.M., Lah, J.J., Leverenz, J.B., Levey, A.I., Li, G., Lieberman, A.P., Lunetta, K.L., Lyketsos, C.G., Marson, D.C., Martiniuk, F., Mash, D.C., Masliah, E., McCormick, W.C., McCurry, S.M., McDavid, A.N., McKee, A.C., Mesulam, M., Miller, B.L., Miller, C.A., Miller, J.W., Morris, J.C., Murrell, J.R., Myers, A.J., O'Bryant, S., Olichney, J.M., Pankratz, V.S., Parisi, J.E., Paulson, H.L., Perry, W., Peskind, E., Pierce, A., Poon, W.W., Potter, H., Quinn, J.F., Raj, A., Raskind, M., Reisberg, B., Reitz, C., Ringman, J.M., Roberson, E.D., Rogaeva, E., Rosen, H.J., Rosenberg, R.N., Sager, M.A., Saykin, A.J., Schneider, J.A., Schneider, L.S., Seeley, W.W., Smith, A.G., Sonnen, J.A., Spina, S., Stern, R.A., Swerdlow, R.H., Tanzi, R.E., Thornton-Wells, T.A., Trojanowski, J.Q., Troncoso, J.C., Van Deerlin, V.M., Van Eldik, L.J., Vinters, H.V., Vonsattel, J.P., Weintraub, S., Welsh-Bohmer, K.A., Wilhelmsen, K.C., Williamson, J., Wingo, T.S., Woltjer, R.L., Wright, C.B., Yu, C.E., Yu, L., Garzia, F., Golamaully, F., Septier, G., Engelborghs, S., Vandenberghe, R., De Deyn, P.P., Fernadez, C.M., Benito, Y.A., Thonberg, H., Forsell, C., Lilius, L., Kinhult-Stählbom, A., Kilander, L., Brundin, R., Concari, L., Helisalmi, S., Koivisto, A.M., Haapasalo, A., Dermecourt, V., Fievet, N., Hanon, O., Dufouil, C., Brice, A., Ritchie, K., Dubois, B., Himali, J.J., Keene, C.D., Tschanz, J., Fitzpatrick, A.L., Kukull, W.A., Norton, M., Aspelund, T., Larson, E.B., Munger, R., Rotter, J.I., Lipton, R.B., Bullido, M.J., Hofman, A., Montine, T.J., Coto, E., Boerwinkle, E., Petersen, R.C., Alvarez, V., Rivadeneira, F., Reiman, E.M., Gallo, M., O'Donnell, C.J., Reisch, J.S., Bruni, A.C., Royall, D.R., Dichgans, M., Sano, M., Galimberti, D., St George-Hyslop, P., Scarpini, E., Tsuang, D.W., Mancuso, M., Bonuccelli, U., Winslow, A.R., Daniele, A., Wu, C.K., Peters, O., Nacmias, B., Riemenschneider, M., Heun, R., Brayne, C., Rubinsztein, D.C., Bras, J., Guerreiro, R., Al-Chalabi, A., Shaw, C.E., Collinge, J., Mann, D., Tsolaki, M., Clarimón, J., Sussams, R., Lovestone, S., O'Donovan, M.C., Owen, M.J., Behrens, T.W., Mead, S., Goate, A.M., Uitterlinden, A.G., Holmes, C., Cruchaga, C., Ingelsson, M., Bennett, D.A., Powell, J., Golde, T.E., Graff, C., De Jager, P.L., Morgan, K., Ertekin-Taner, N., Combarros, O., Psaty, B.M., Passmore, P., Younkin, S.G., Berr, C., Gudnason, V., Rujescu, D., Dickson, D.W., Dartigues, J.F., DeStefano, A.L., Ortega-Cubero, S., Hakonarson, H., Campion, D., Boada, M., Kauwe, J.K., Farrer, L.A., Van Broeckhoven, C., Ikram, M.A., Jones, L., Haines, J.L., Tzourio, C., Launer, L.J., Escott-Price, V., Mayeux, R., Deleuze, J.F., Amin, N., Holmans, P.A., Pericak-Vance, M.A., Amouyel, P., van Duijn, C.M., Ramirez, A., Wang, L.S., Lambert, J.C., Seshadri, S., Williams, J., Schellenberg, G.D., Peloso, Gina M., van der Lee, Sven J., Destefano, Anita L., and Seshardi, Sudha
- Published
- 2018
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16. SU102META-ANALYSIS OF CLOZAPINE-ASSOCIATED NEUTROPENIA AND AGRANULOCYTOSIS
- Author
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Konte, Bettina, primary, Walters, J.T., additional, Giegling, I., additional, Legge, S., additional, Pardiñas, A.F., additional, Cohen, D., additional, Pirmohamed, M., additional, Tiihonen, J., additional, Hartmann, A.M., additional, Bogers, J.P., additional, van der Weide, J., additional, van der Weide, K., additional, Putkonen, A., additional, Repo-Tiihonen, E., additional, Hallikainen, T., additional, Silva, E., additional, Ingimarsson, O., additional, Sigurdsson, E., additional, Kennedy, James L., additional, Breen, Gerome, additional, Sullivan, Patrick, additional, Rietschel, Marcella, additional, Stefansson, Hreinn, additional, Collier, D.A., additional, O'Donovan, Michael, additional, and Rujescu, Dan, additional
- Published
- 2019
- Full Text
- View/download PDF
17. Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease
- Author
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Peloso, G.M. (Gina M.), Lee, S.J. (Sven) van der, Sims, R. (Rebecca), van der Lee, S.J. (S. J.), Naj, A.C. (A. C.), Bellenguez, C. (Céline), Badarinarayan, N. (Nandini), Jakobsdottir, M. (Margret), Kunkle, B.W. (B. W.), Boland, A. (A.), Raybould, R. (R.), Bis, J.C. (Joshua), Martin, E.R. (E. R.), Grenier-Boley, B. (Benjamin), Heilmann-Heimbach, S. (S.), Chouraki, V. (V.), Kuzma, A.B. (A. B.), Sleegers, K. (K.), Vronskaya, M., Ruiz, A. (A.), Graham, R.R. (Robert), Olaso, R. (Robert), Hoffmann, P. (Per), Grove, M.L. (Megan), Vardarajan, B.N. (Badri), Hiltunen, M. (Mikko), Nöthen, M.M. (Markus), White, C.C. (Charles), Hamilton-Nelson, K.L. (K. L.), Epelbaum, J. (Jacques), Maier, W. (Wolfgang), Choi, S.H. (S. H.), Beecham, G.W., Dulary, C. (C.), Herms, S. (Stefan), Smith, A.V. (Albert), Funk, C.C. (C. C.), Derbois, (), Forstner, A.J. (Andreas), Ahmad, S. (S.), Li, H. (Huaixing), Bacq, D. (D.), Harold, D. (D.), Satizabal, C.L. (Claudia), Valladares, O. (Otto), Squassini, A. (Alessio), Thomas, R. (R.), Brody, J.A. (Jennifer A.), Qu, L. (Liming), Sanchez-Juan, P. (Pascual), Morgan, T. (Thomas), Wolters, F.J. (Frank), Zhao, Y. (Y.), Garcia, F.S. (F. S.), Denning, N. (Nicola), Fornage, M. (Myriam), Malamon, J. (J.), Naranjo, M.C.D. (M. C.D.), Majounie, E. (Elisa), Mosley, T.H. (Thomas H.), Dombroski, B. (B.), Wallon, D. (David), Lupton, M.K. (Michelle), Dupuis, J. (Josée), Whitehead, P. (P.), Fratiglioni, L. (L.), Medway, C. (Christopher), Jian, X. (X.), Mukherjee, S. (S.), Keller, L. (L.), Brown, K. (Kristelle), Lin, H. (Honghuang), Cantwell, L.B. (Laura B.), Panza, F. (F.), McGuinness, B. (B.), Moreno-Grau, S. (S.), Burgess, J.D. (J. D.), Solfrizzi, V. (Vincenzo), Proitsi, P. (P.), Adams, H.H.H. (Hieab), Allen, M. (M.), Seripa, D. (Davide), Pastor, P. (P.), Cupples, L.A. (L. A.), Price, N.D. (N. D.), Hannequin, D. (Didier), Frank-Garcia, A. (Ana), Levy, D. (D.), Chakrabarty, P. (P.), Caffarra, P. (Paolo), Giegling, I. (Ina), Beiser, A. (Alexa), Giedraitis, V. (Vilmantas), Hampel, H. (Heather), Garcia, M.E. (M.), Wang, X. (X.), Lannfelt, L. (Lars), Mecocci, P. (Patrizia), Eiriksdottir, G. (Gudny), Crane, L.M.A., Pasquier, F. (Florence), Boccardi, V. (V.), Henández, I. (I.), Barber, R.C. (R. C.), Scherer, M. (M.), Tárraga, L. (L.), Adams, P.M. (P. M.), Leber, I. (Isabelle), Chen, Y.D.I. (Yii-Der Ida), Albert, M. (Michael), Riedel-Heller, S. (Steffi), Emilsson, V. (Valur), Beekly, D. (D.), Braae, A. (A.), Schmidt, R. (R.), Blacker, D. (D.), Masullo, C., Schmidt, H. (Helena), Doody, R.S. (R. S.), Spalletta, G. (Gianfranco), Longstreth Jr, W.T., Fairchild, T.J. (T. J.), Bossù, P. (P.), Lopez, O.L. (Oscar), Frosch, M.P. (Matthew), Sacchinelli, E. (E.), Ghetti, B. (Bernardino), Yang, Q. (Qiong Fang), Huebinger, R.M. (R. M.), Jessen, F., Li, S. (S.), Kamboh, M.I. (M. I.), Morris, J. (J.), Sotolongo-Grau, O. (O.), Katz, M.J. (M. J.), Corcoran, C. (C.), Dunstan, M.L., Braddel, A. (A.), Thomas, C. (C.), Meggy, A. (A.), Marshall, R. (R.), Gerrish, A. (Amy), Chapman, J. (Jade), Aguilar, M. (M.), Taylor, S. (S.), Hill, M. (M.), Fairén, M.D. (M. D.), Hodges, A. (A.), Vellas, B. (B.), Soininen, H. (H.), Kloszewska, I. (Iwona), Daniilidou, M. (M.), Uphill, J. (James), Patel, Y. (Y.), Hughes, J.T. (J. T.), Lord, J. (J.), Turton, J.C. (James), Hartmann, A.M. (A. M.), Cecchetti, R. (R.), Fenoglio, C. (Chiara), Serpente, M. (Maria), Arcaro, M. (M.), Caltagirone, C. (C.), Orfei, M.D. (M. D.), Ciaramella, A. (A.), Pichler, I. (Irene), Mayhaus, M. (Manuel), Gu, W. (W.), Lleo, A. (Alberto), Fortea, J. (J.), Blesa, R. (Rafael), Barber, I.S. (I. S.), Brookes, K. (K.), Cupidi, C. (Chiara), Maletta, R. (Raffaele), Carrell, D. (D.), Sorbi, S. (Sandro), Moebus, S. (Susanne), Urbano, M. (M.), Pilotto, A. (Alberto), Kornhuber, J. (Johannes), Bosco, P. (Paolo), Todd, S. (S.), Craig, D. (D.), Johnston, J. (J.), Gill, M. (M.), Lawlor, B.A. (B.), Lynch, A. (Aoibhinn), Fox, N.C. (Nick), Hardy, J. (J.), Albin, R.L. (R. L.), Apostolova, L.G. (L. G.), Arnold, S.E. (Steven), Asthana, S. (S.), Atwood, C.S. (Craig), Baldwin, C. (Clinton), Barnes, L.L. (L. L.), Barral, S. (Sandra), Beach, T.G. (Thomas), Becker, J.T. (James), Bigio, E.H. (Eileen), Bird, T.D. (T. D.), Boeve, B.F. (Bradley), Bowen, J.D. (J. D.), Boxer, A.L. (Adam), Burke, J.R. (J. R.), Burns, J.M. (J. M.), Buxbaum, J.D. (J. D.), Cairns, N.J. (N. J.), Cao, C. (C.), Carlson, C. (Chris), Carlsson, C.M. (C. M.), Carney, R.M. (R. M.), Carrasquillo, M.M. (M. M.), Carroll, S.L. (Steven), Diaz, C.C. (C. C.), Chui, H.C. (H. C.), Clark, D.G. (D. G.), Cribbs, D.H. (D. H.), Crocco, E.A. (E. A.), DeCarli, C. (Charles), Dick, M. (M.), Duara, R. (R.), Evans, D.A. (D. A.), Faber, K.M. (Kelley), Fallon, K.B. (K. B.), Fardo, D.W. (D. W.), Farlow, M.R. (M. R.), Ferris, S. (S.), Foroud, T.M. (T. M.), Galasko, D.R. (D. R.), Gearing, M. (Marla), Geschwind, H., Gilbert, J.R. (John R.), Graff-Radford, N.R. (Neill), Green, R.C. (Robert), Growdon, J.H. (J. H.), Hamilton, R.L. (Ronald L.), Harrell, L.E. (L. E.), Honig, L.S. (L. S.), Huentelman, M.J. (M. J.), Hulette, C. (Christine), Hyman, B.T. (Bradley), Jarvik, G.P. (Gail), Abner, E. (E.), Jin, L.W. (L. W.), Jun, G. (G.), Karydas, A. (A.), Kaye, J.A. (Jeffrey), Kim, R. (R.), Kowall, N.W. (N. W.), Kramer, J.H. (Joel), LaFerla, F.M. (F. M.), Lah, J.J. (J. J.), Leverenz, J.B. (J. B.), Levey, A.I. (Allan), Li, G. (Guo), Lieberman, A.P. (A. P.), Lunetta, K.L. (Kathryn), Lyketsos, C.G. (C. G.), Marson, D.C. (D. C.), Martiniuk, F. (F.), Mash, D.C. (Deborah C.), Masliah, E. (Eliezer), McCormick, W.C. (W. C.), McCurry, S.M. (S. M.), McDavid, A.N. (A. N.), McKee, A.C. (A. C.), Mesulam, M. (Marsel), Miller, B.L. (Bruce Lars), Miller, C.A. (C. A.), Miller, J.W. (J. W.), Morris, H. (Huw), Myers, A.J. (Amanda J.), O'Bryant, S. (S.), Olichney, J.M. (J. M.), Pankratz, V.S. (Shane), Parisi, J.E. (Joseph), Paulson, H.L. (Henry), Perry, W. (W.), Peskind, E. (E.), Pierce, A. (A.), Poon, W.W. (W. W.), Potter, H. (H.), Quinn, J.F. (J. F.), Raj, A. (A.), Raskind, M. (M.), Reisberg, B. (B.), Reitz, C. (C.), Ringman, J.M. (J. M.), Roberson, E.D. (E. D.), Rogaeva, E. (Ekaterina), Rosen, H.J. (H. J.), Rosenberg, R.N. (Roger), Sager, M.A. (M. A.), Saykin, A.J. (Andrew), Schneider, J.A. (Julie), Schneider, L.S. (L. S.), Seeley, W.W. (W. W.), Smith, A.G. (A. G.), Sonnen, J.A. (J. A.), Spina, S. (S.), Stern, R.A. (R. A.), Swerdlow, R.H. (R. H.), Tanzi, R.E. (R. E.), Thornton-Wells, T.A. (Tricia), Trojanowski, J.Q. (J. Q.), Troncoso, J.C. (J. C.), Deerlin, V.M. (Vivianna), Van Eldik, L.J. (L. J.), Vinters, H.V. (Harry), Vonsattel, J.P. (Jean Paul), Weintraub, S. (Sandra), Welsh-Bohmer, K.A. (Kathleen), Wilhelmsen, K.C., Williamson, J. (J.), Wingo, T.S. (T. S.), Woltjer, R.L. (Randall), Wright, C.B. (Clinton B.), Yu, C.E. (C. E.), Yu, L. (L.), Garzia, F. (F.), Golamaully, F. (F.), Septier, G. (G.), Engelborghs, S. (Sebastiaan), Vandenberghe, R. (Rik), Deyn, P.P. (Peter) de, Fernadez, C.M. (C. M.), Benito, Y.A. (Y. A.), Thonberg, H. (Håkan), Forsell, C. (C.), Lilius, L. (Lena), Kinhult-Stählbom, A. (A.), Kilander, L. (L.), Brundin, R. (R.), Concari, L. (L.), Helisalmi, S. (S.), Koivisto, A.M. (A. M.), Haapasalo, A. (Annakaisa), Dermecourt, V. (V.), Fievet, N. (N.), Hanon, O. (Olivier), Dufouil, C. (Carole), Brice, A., Ritchie, K. (Karen), Dubois, B. (B.), Himali, J.J. (Jayandra), Keene, C.D. (C. D.), Tschanz, J. (J.), Fitzpatrick, A.L. (Annette), Kukull, W.A., Norton, M. (M.), Aspelund, T. (Thor), Larson, E.B. (Eric B.), Munger, R. (R.), Rotter, J.I. (Jerome I.), Lipton, R.B. (R. B.), Bullido, M.J. (Maria), Hofman, A. (A.), Montine, T.J. (T. J.), Coto, E. (Eliecer), Boerwinkle, E. (E.), Petersen, R.C. (R. C.), Alvarez, V. (V.), Rivadeneira Ramirez, F. (Fernando), Reiman, E.M. (Eric), Gallo, V. (Valentina), O'Donnell, C.J. (Christopher), Reisch, J.S. (J. S.), Bruni, A.C. (Amalia), Royall, D.R. (D. R.), Kubisch, C. (Christian), Sano, M. (M.), Galimberti, D. (Daniela), St. George-Hyslop, P. (Peter), Scarpini, E. (Elio), Tsuang, D.W. (Debby W.), Mancuso, M. (M.), Bonuccelli, U. (Ubaldo), Winslow, A.R. (A. R.), Daniele, A. (A.), Wu, C.K. (C. K.), Peters, O. (Oscar), Nacmias, B. (Benedetta), Riemenschneider, M. (M.), Heun, R. (Reinhard), Brayne, C. (Carol), Rubinsztein, D.C. (David), Bras, J. (J.), Guerreiro, R. (R.), Al-Chalabi, A. (Ammar), Shaw, C.E. (C. E.), Collinge, J. (J.), Mann, D. (D.), Tsolaki, M. (Magda), Clarimón, J. (J.), Sussams, R. (R.), Lovestone, S. (Simon), O'donovan, M.C. (Michael), Owen, M.J. (Michael), Behrens, T.W. (Timothy), Mead, S. (S.), Goate, A.M. (Alison), Uitterlinden, A.G. (A. G.), Holmes, C. (C.), Cruchaga, C. (Carlos), Ingelsson, M. (Martin), Bennett, D.A. (David), Powell, J. (J.), Golde, T.E. (T. E.), Graff, C. (C.), De Jager, P., Morgan, K. (Kevin), Ertekin-Taner, N. (N.), Combarros, O. (Onofre), Psaty, B.M. (Bruce), Passmore, P. (P.), Younkin, S.G. (S. G.), Berr, C. (Claudine), Gudnason, V. (Vilmundur), Rujescu, D. (D.), Dickson, D. (Dennis), Dartigues, J.-F., DeStefano, A.L. (Anita), Ortega-Cubero, S. (S.), Hakonarson, H. (Hakon), Campion, D. (Dominique), Boada, M. (M.), Kauwe, J.K. (J. K.), Farrer, L.A. (Lindsay), Broeckhoven, C. (Christine) van, Ikram, M.A. (Arfan), Jones, L. (L.), Haines, J.L. (Jonathan), Tzourio, C. (Christophe), Launer, L.J. (Lenore), Escott-Price, V. (V.), Mayeux, R. (R.), Deleuze, J.-F. (Jean-François), Amin, N. (Najaf), Holmans, P.A. (Peter A.), Kunkle, B. (Brian), Amouyel, P. (Philippe), Duijn, C.M. (Cornelia) van, Ramirez, A. (Alfredo), Wang, L.S. (L. S.), Lambert, J.-C. (J.), Seshadri, S. (Sudha), Williams, J. (J.), Schellenberg, G.D. (Gerard), Destefano, A.L. (Anita L.), Seshardi, S. (Sudha), Peloso, G.M. (Gina M.), Lee, S.J. (Sven) van der, Sims, R. (Rebecca), van der Lee, S.J. (S. J.), Naj, A.C. (A. C.), Bellenguez, C. (Céline), Badarinarayan, N. (Nandini), Jakobsdottir, M. (Margret), Kunkle, B.W. (B. W.), Boland, A. (A.), Raybould, R. 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(N.), Hanon, O. (Olivier), Dufouil, C. (Carole), Brice, A., Ritchie, K. (Karen), Dubois, B. (B.), Himali, J.J. (Jayandra), Keene, C.D. (C. D.), Tschanz, J. (J.), Fitzpatrick, A.L. (Annette), Kukull, W.A., Norton, M. (M.), Aspelund, T. (Thor), Larson, E.B. (Eric B.), Munger, R. (R.), Rotter, J.I. (Jerome I.), Lipton, R.B. (R. B.), Bullido, M.J. (Maria), Hofman, A. (A.), Montine, T.J. (T. J.), Coto, E. (Eliecer), Boerwinkle, E. (E.), Petersen, R.C. (R. C.), Alvarez, V. (V.), Rivadeneira Ramirez, F. (Fernando), Reiman, E.M. (Eric), Gallo, V. (Valentina), O'Donnell, C.J. (Christopher), Reisch, J.S. (J. S.), Bruni, A.C. (Amalia), Royall, D.R. (D. R.), Kubisch, C. (Christian), Sano, M. (M.), Galimberti, D. (Daniela), St. George-Hyslop, P. (Peter), Scarpini, E. (Elio), Tsuang, D.W. (Debby W.), Mancuso, M. (M.), Bonuccelli, U. (Ubaldo), Winslow, A.R. (A. R.), Daniele, A. (A.), Wu, C.K. (C. K.), Peters, O. (Oscar), Nacmias, B. (Benedetta), Riemenschneider, M. (M.), Heun, R. (Reinhard), Brayne, C. (Carol), Rubinsztein, D.C. (David), Bras, J. (J.), Guerreiro, R. (R.), Al-Chalabi, A. (Ammar), Shaw, C.E. (C. E.), Collinge, J. (J.), Mann, D. (D.), Tsolaki, M. (Magda), Clarimón, J. (J.), Sussams, R. (R.), Lovestone, S. (Simon), O'donovan, M.C. (Michael), Owen, M.J. (Michael), Behrens, T.W. (Timothy), Mead, S. (S.), Goate, A.M. (Alison), Uitterlinden, A.G. (A. G.), Holmes, C. (C.), Cruchaga, C. (Carlos), Ingelsson, M. (Martin), Bennett, D.A. (David), Powell, J. (J.), Golde, T.E. (T. E.), Graff, C. (C.), De Jager, P., Morgan, K. (Kevin), Ertekin-Taner, N. (N.), Combarros, O. (Onofre), Psaty, B.M. (Bruce), Passmore, P. (P.), Younkin, S.G. (S. G.), Berr, C. (Claudine), Gudnason, V. (Vilmundur), Rujescu, D. (D.), Dickson, D. (Dennis), Dartigues, J.-F., DeStefano, A.L. (Anita), Ortega-Cubero, S. (S.), Hakonarson, H. (Hakon), Campion, D. (Dominique), Boada, M. (M.), Kauwe, J.K. (J. K.), Farrer, L.A. (Lindsay), Broeckhoven, C. (Christine) van, Ikram, M.A. (Arfan), Jones, L. (L.), Haines, J.L. (Jonathan), Tzourio, C. (Christophe), Launer, L.J. (Lenore), Escott-Price, V. (V.), Mayeux, R. (R.), Deleuze, J.-F. (Jean-François), Amin, N. (Najaf), Holmans, P.A. (Peter A.), Kunkle, B. (Brian), Amouyel, P. (Philippe), Duijn, C.M. (Cornelia) van, Ramirez, A. (Alfredo), Wang, L.S. (L. S.), Lambert, J.-C. (J.), Seshadri, S. (Sudha), Williams, J. (J.), Schellenberg, G.D. (Gerard), Destefano, A.L. (Anita L.), and Seshardi, S. (Sudha)
- Abstract
Introduction: There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C. Methods: Ten single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger. Results: Based on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P >.7). Discussion: Our study does not support the role of HDL-C on risk of AD through HDL-C altered b
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- 2018
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18. Age at first birth in women is genetically associated with increased risk of schizophrenia
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Ni, G. (Guiyan), Gratten, J. (Jacob), Wray, N.R. (Naomi R.), Lee, S.H. (Sang Hong), Ripke, S. (Stephan), Neale, B.M. (Benjamin), Corvin, A. (Aiden), Walters, J.T. (James), Farh, K.-H. (Kai-How), Holmans, P.A. (Peter A.), Lee, P.H. (Phil H.), Bulik-Sullivan, B.K. (Brendan), Collier, D.A. (David), Huang, H. (Hailiang), Pers, T.H. (Tune), Agartz, I. (Ingrid), Agerbo, E. (Esben), Albus, M. (Margot), Alexander, M. (Madeline), Amin, F. (Farooq), Bacanu, S.A. (Silviu), Begemann, M. (Martin), Belliveau, R.A. (Richard A.), Bene, J. (Judit), Bergen, S.E. (Sarah), Bevilacqua, E. (Elizabeth), Bigdeli, T.B. (Tim B.), Black, D.W. (Donald), Bruggeman, R. (Richard), Buccola, N.G. (Nancy G), Buckner, M., Byerley, W.F. (William F), Cahn, W. (Wiepke), Cai, G. (Guiqing), Campion, D. (Dominique), Cantor, R.M., Carr, V.J. (Vaughan J.), Carrera, N. (Noa), Catts, S.V. (Stanley), Chambert, K. (Kimberly), Chan, R.C.K. (Raymond C. K.), Chen, R.Y.L. (Ronald Y.), Chen, E.Y.H. (Eric Y. H.), Cheng, W. (Wei), Cheung, E.F.C. (Eric F. C.), Chong, S.A. (Siow Ann), Cloninger, C.R. (C Robert), Cohen, D.J. (David J.), Cohen, N. (Nadine), Cormican, P. (Paul), Craddock, N.J. (Nick), Crowley, J.J. (James), Curtis, D. (David), Davidson, M.W. (Michael ), Davis, K.L. (Kenneth), Degenhardt, F., Del-Favero, J. (Jurgen), Demontis, D. (Ditte), Dikeos, D. (Dimitris), Dinan, T. (Timothy), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drapeau, E. (Elodie), Duan, J. (Jubao), Dudbridge, F. (Frank), Durmishi, N. (Naser), Eichhammer, P. (Peter), Hagen, K. (Knut), Escott-Price, V. (Valentina), Essioux, L. (Laurent), Fanous, A.H. (Ayman H.), Farrell, M.S. (Martilias), Frank, J. (Josef), Franke, L. (Lude), Freedman, R. (Robert), Freimer, N.B. (Nelson), Friedl, M., Friedman, J.I. (Joseph), Fromer, M. (Menachem), Genovese, G. (Giulio), Georgieva, I. (Irina), Giegling, I. (Ina), Giusti-Rodríguez, P. (Paola), Godard, S. (Stephanie), Goldstein, J.I. (Jacqueline), Golimbet, V. (Vera), Gopal, R. (Robin), Haan, L. 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(Jan), Lönnqvist, J. (Jouko), Macek, M. (Milan MI), Magnusson, P.K. (Patrik), Maher, B.S. (Brion), Maier, W. (Wolfgang), Mallet, V. (Vincent), Marsal, S. (Sara), Mattheisen, M. (Manuel), Mattingsdal, M. (Morten), McCarley, R.W. (Robert), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Meier, S., Meijer, C. (Carin), Melegh, B. (Bela), Melle, I. (Ingrid), Mesholam-Gately, R.I. (Raquelle), Metspalu, A. (Andres), Michie, P.T. (Patricia), Milani, L. (Lili), Milanova, V. (Vihra), Mokrab, Y. (Younes), Morris, D.W. (Derek W.), Mors, O., Murphy, K.C. (Kieran), Murray, R. (Robin), Myin-Germeys, I. (Inez), Müller-Myhsok, B. (B.), Nelis, M. (Mari), Nenadic, I. (Igor), Nertney, D.A. (Deborah), Nestadt, G. (Gerald), Nicodemus, K.K. (Kristin), Nikitina-Zake, L. (Liene), Nisenbaum, L. (Laura), Nordin, A. (Annelie), O'Callaghan, E. (Eadbhard), O'Dushlaine, C. (Colm), O'neill, F.A. (F. Anthony), Oh, S.-Y. (Sang-Yun), Olincy, A. (Ann), Olsen, L. (Line), Os, J.V. (Jim Van), Pantelis, C. (Christos), Papadimitriou, G.N. (George), Papiol, S. (Sergi), Parkhomenko, E. (Elena), Pato, C. (Carlos), Paunio, T. (Tiina), Pejovic-Milovancevic, M. (Milica), Perkins, D.O. (Diana O.), Pietiläinen, O.P.H. (Olli), Pimm, J. (Jonathan), Pocklington, A.J. (Andrew), Powell, J. (John), Price, A. (Alkes), Pulver, A.E. (Ann), Purcell, S.M. (Shaun M.), Quested, D.J. (Digby J), Rasmussen, H.B. (Henrik B), Reichenberg, A. (Abraham), Reimers, B. (Bernhard), Richards, A. (Alex), Roffman, J.L. (Joshua), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Schall, J.D. (Jeffrey), Schubert, C.R. (Christian R.), Schulze, T.G. (Thomas), Schwab, S.G. (Sibylle G.), Scolnick, E. (Edward), Scott, R.J. (Rodney J.), Seidman, L.J. (Larry), Shi, J. (Jianxin), Sigurdsson, E. (Engilbert), Silagadze, T. (Teimuraz), Silverman, J.M. (Jeremy M.), Sim, K. (Kang), Slominsky, P. (Petr), Smoller, J.W., So, H.-C. (Hon-Cheong), Spencer, C.C.A. (Chris C.), Stahl, E.A. (Eli A.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Stogmann, E. (Elisabeth), Straub, R.E. (Richard), Strengman, E. (Eric), Strohmaier, J. (Jana), Stroup, T.S. (T. Scott), Subramaniam, V. (Venkat), Suvisaari, J. (Jaana), Svrakic, D.M. (Dragan), Szatkiewicz, J.P. (Jin P.), Söderman, E. (Erik), Thirumalai, S. (Srinivasa), Toncheva, D. (Draga), Tosato, S. (Sarah), Veijola, J. (Juha), Waddington, J. (John), Walsh, D. (Dermot), Wang, D. (Dai), Wang, Q. (Qiang), Webb, B.T. (Bradley T.), Weiser, M. (Mark), Wildenauer, D.B. (Dieter), Williams, N.M. (Nigel M.), Williams, S. (Stephanie), Witt, S.H. (Stephanie H), Wolen, A.R. (Aaron), Wong, E.H.M. (Emily H.M.), Wormley, B.K. (Brandon K.), Xi, H.S. (Hualin Simon), Zai, C.C. (Clement C.), Zheng, X. (Xuebin), Zimprich, F. (Fritz), Zwart, J-A. (John-Anker), Visscher, P.M. (Peter), Adolfsson, R., Andreassen, O.A. (Ole), Blackwood, D.H.R. (Douglas), Bramon, E. (Elvira), Buxbaum, J.D. (Joseph D.), Borglum, A.D. (Anders), Cichon, S. (Sven), Darvasi, A. (Ariel), Domenici, E. (Enrico), Ehrenreich, H. (Hannelore), Esko, T. (Tõnu), Gejman, P.V. (Pablo), Gill, M. (Michael), Gurling, H. (Hugh), Hultman, C.M. (Christina), Iwata, N. (Nakao), Jablensky, A. (Assen), Jönsson, E.G. (Erik), Kendler, K. (K.), Kirov, G. (George), Knight, J. (Jo), Lencz, T. (Todd), Levinson, D.F. (Douglas F.), Li, Q.S. (Qingqin S.), Liu, J. (Jianjun), Malhotra, A.K. (Anil K), McCarroll, S.A. (Steve), McQuillin, A. (Andrew), Moran, J.L. (Jennifer L.), Mortensen, P.B., Mowry, B.J. (Bryan J), Nöthen, M.M. (Markus), Ophoff, R.A. (Roel), Owen, M.J. (Michael), Palotie, A. (Aarno), Petryshen, T.L. (Tracey L.), Posthuma, D. (Danielle), Rietschel, M. (Marcella), Riley, B.P. (Brien P.), Rujescu, D. (Dan), Sham, P.C. (Pak C.), Sklar, P. (Pamela), Clair, D.S., Weinberger, D.R. (Daniel), Wendland, A. (Annika), Werge, T.M. (Thomas), Daly, M.J. (Mark J.), Sullivan, P.F. (Patrick), O'donovan, M.C. (Michael), Ni, G. (Guiyan), Gratten, J. (Jacob), Wray, N.R. (Naomi R.), Lee, S.H. (Sang Hong), Ripke, S. (Stephan), Neale, B.M. (Benjamin), Corvin, A. (Aiden), Walters, J.T. (James), Farh, K.-H. (Kai-How), Holmans, P.A. (Peter A.), Lee, P.H. (Phil H.), Bulik-Sullivan, B.K. (Brendan), Collier, D.A. (David), Huang, H. (Hailiang), Pers, T.H. (Tune), Agartz, I. (Ingrid), Agerbo, E. (Esben), Albus, M. (Margot), Alexander, M. (Madeline), Amin, F. (Farooq), Bacanu, S.A. (Silviu), Begemann, M. (Martin), Belliveau, R.A. (Richard A.), Bene, J. (Judit), Bergen, S.E. (Sarah), Bevilacqua, E. (Elizabeth), Bigdeli, T.B. (Tim B.), Black, D.W. (Donald), Bruggeman, R. (Richard), Buccola, N.G. (Nancy G), Buckner, M., Byerley, W.F. (William F), Cahn, W. (Wiepke), Cai, G. (Guiqing), Campion, D. (Dominique), Cantor, R.M., Carr, V.J. (Vaughan J.), Carrera, N. (Noa), Catts, S.V. (Stanley), Chambert, K. (Kimberly), Chan, R.C.K. (Raymond C. K.), Chen, R.Y.L. (Ronald Y.), Chen, E.Y.H. (Eric Y. H.), Cheng, W. (Wei), Cheung, E.F.C. (Eric F. C.), Chong, S.A. (Siow Ann), Cloninger, C.R. (C Robert), Cohen, D.J. (David J.), Cohen, N. (Nadine), Cormican, P. (Paul), Craddock, N.J. (Nick), Crowley, J.J. (James), Curtis, D. (David), Davidson, M.W. (Michael ), Davis, K.L. (Kenneth), Degenhardt, F., Del-Favero, J. (Jurgen), Demontis, D. (Ditte), Dikeos, D. (Dimitris), Dinan, T. (Timothy), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drapeau, E. (Elodie), Duan, J. (Jubao), Dudbridge, F. (Frank), Durmishi, N. (Naser), Eichhammer, P. (Peter), Hagen, K. (Knut), Escott-Price, V. (Valentina), Essioux, L. (Laurent), Fanous, A.H. (Ayman H.), Farrell, M.S. (Martilias), Frank, J. (Josef), Franke, L. (Lude), Freedman, R. (Robert), Freimer, N.B. (Nelson), Friedl, M., Friedman, J.I. (Joseph), Fromer, M. (Menachem), Genovese, G. (Giulio), Georgieva, I. (Irina), Giegling, I. (Ina), Giusti-Rodríguez, P. (Paola), Godard, S. (Stephanie), Goldstein, J.I. (Jacqueline), Golimbet, V. (Vera), Gopal, R. (Robin), Haan, L. (Lieuwe) de, Hammer, C. (Christian), Hamshere, M.L. (Marian), Hansen, M. (Mark), Hansen, T. (Thomas), Haroutunian, V. (Vahram), Hartmann, A.M. (Annette M.), Henskens, F.A. (Frans), Herms, S. (Stefan), Hirschhorn, J.N. (Joel), Hoffmann, P. (Per), Hofman, A. (Andrea), Hollegaard, M.V. (Mads V), Hougaard, D.M. (David), Ikeda, M. (Masashi), Joa, I. (Inge), Juliá, A. (Antonio), Kahn, R. (René), Kalaydjieva, L. (Luba), Karachanak-Yankova, S. (Sena), Karjalainen, J. (Juha), Kavanagh, D. (David), Keller, M.C. (Matthew C), Kennedy, J.L., Khrunin, A. (Andrey), Kim, Y. (Yunjung), Klovins, J. (Janis), Knowles, J.A. (James A), Konte, B. (Bettina), Kučinskas, V. (Vaidutis), Kucinskiene, Z.A. (Zita Ausrele), Kuzelova-Ptackova, H. (Hana), Kähler, J. (Jan), Laurent, C. (Camille), Keong, J.L.C. (Jimmy Lee Chee), Legge, S.E. (Sophie), Lerer, B. (Bernard), Li, M. (Miaoxin), Li, T. (Tao), Liang, K.-Y. (Kung-Yee), Lieberman, A.P. (Andrew), Limborska, S. (Svetlana), Loughland, C.M. (Carmel), Lubinski, J. (Jan), Lönnqvist, J. (Jouko), Macek, M. (Milan MI), Magnusson, P.K. (Patrik), Maher, B.S. (Brion), Maier, W. (Wolfgang), Mallet, V. (Vincent), Marsal, S. (Sara), Mattheisen, M. (Manuel), Mattingsdal, M. (Morten), McCarley, R.W. (Robert), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Meier, S., Meijer, C. (Carin), Melegh, B. (Bela), Melle, I. (Ingrid), Mesholam-Gately, R.I. (Raquelle), Metspalu, A. (Andres), Michie, P.T. (Patricia), Milani, L. (Lili), Milanova, V. (Vihra), Mokrab, Y. (Younes), Morris, D.W. (Derek W.), Mors, O., Murphy, K.C. (Kieran), Murray, R. (Robin), Myin-Germeys, I. (Inez), Müller-Myhsok, B. (B.), Nelis, M. (Mari), Nenadic, I. (Igor), Nertney, D.A. (Deborah), Nestadt, G. (Gerald), Nicodemus, K.K. (Kristin), Nikitina-Zake, L. (Liene), Nisenbaum, L. (Laura), Nordin, A. (Annelie), O'Callaghan, E. (Eadbhard), O'Dushlaine, C. (Colm), O'neill, F.A. (F. Anthony), Oh, S.-Y. (Sang-Yun), Olincy, A. (Ann), Olsen, L. (Line), Os, J.V. (Jim Van), Pantelis, C. (Christos), Papadimitriou, G.N. (George), Papiol, S. (Sergi), Parkhomenko, E. (Elena), Pato, C. (Carlos), Paunio, T. (Tiina), Pejovic-Milovancevic, M. (Milica), Perkins, D.O. (Diana O.), Pietiläinen, O.P.H. (Olli), Pimm, J. (Jonathan), Pocklington, A.J. (Andrew), Powell, J. (John), Price, A. (Alkes), Pulver, A.E. (Ann), Purcell, S.M. (Shaun M.), Quested, D.J. (Digby J), Rasmussen, H.B. (Henrik B), Reichenberg, A. (Abraham), Reimers, B. (Bernhard), Richards, A. (Alex), Roffman, J.L. (Joshua), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Schall, J.D. (Jeffrey), Schubert, C.R. (Christian R.), Schulze, T.G. (Thomas), Schwab, S.G. (Sibylle G.), Scolnick, E. (Edward), Scott, R.J. (Rodney J.), Seidman, L.J. (Larry), Shi, J. (Jianxin), Sigurdsson, E. (Engilbert), Silagadze, T. (Teimuraz), Silverman, J.M. (Jeremy M.), Sim, K. (Kang), Slominsky, P. (Petr), Smoller, J.W., So, H.-C. (Hon-Cheong), Spencer, C.C.A. (Chris C.), Stahl, E.A. (Eli A.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Stogmann, E. (Elisabeth), Straub, R.E. (Richard), Strengman, E. (Eric), Strohmaier, J. (Jana), Stroup, T.S. (T. Scott), Subramaniam, V. (Venkat), Suvisaari, J. (Jaana), Svrakic, D.M. (Dragan), Szatkiewicz, J.P. (Jin P.), Söderman, E. (Erik), Thirumalai, S. (Srinivasa), Toncheva, D. (Draga), Tosato, S. (Sarah), Veijola, J. (Juha), Waddington, J. (John), Walsh, D. (Dermot), Wang, D. (Dai), Wang, Q. (Qiang), Webb, B.T. (Bradley T.), Weiser, M. (Mark), Wildenauer, D.B. (Dieter), Williams, N.M. (Nigel M.), Williams, S. (Stephanie), Witt, S.H. (Stephanie H), Wolen, A.R. (Aaron), Wong, E.H.M. (Emily H.M.), Wormley, B.K. (Brandon K.), Xi, H.S. (Hualin Simon), Zai, C.C. (Clement C.), Zheng, X. (Xuebin), Zimprich, F. (Fritz), Zwart, J-A. (John-Anker), Visscher, P.M. (Peter), Adolfsson, R., Andreassen, O.A. (Ole), Blackwood, D.H.R. (Douglas), Bramon, E. (Elvira), Buxbaum, J.D. (Joseph D.), Borglum, A.D. (Anders), Cichon, S. (Sven), Darvasi, A. (Ariel), Domenici, E. (Enrico), Ehrenreich, H. (Hannelore), Esko, T. (Tõnu), Gejman, P.V. (Pablo), Gill, M. (Michael), Gurling, H. (Hugh), Hultman, C.M. (Christina), Iwata, N. (Nakao), Jablensky, A. (Assen), Jönsson, E.G. (Erik), Kendler, K. (K.), Kirov, G. (George), Knight, J. (Jo), Lencz, T. (Todd), Levinson, D.F. (Douglas F.), Li, Q.S. (Qingqin S.), Liu, J. (Jianjun), Malhotra, A.K. (Anil K), McCarroll, S.A. (Steve), McQuillin, A. (Andrew), Moran, J.L. (Jennifer L.), Mortensen, P.B., Mowry, B.J. (Bryan J), Nöthen, M.M. (Markus), Ophoff, R.A. (Roel), Owen, M.J. (Michael), Palotie, A. (Aarno), Petryshen, T.L. (Tracey L.), Posthuma, D. (Danielle), Rietschel, M. (Marcella), Riley, B.P. (Brien P.), Rujescu, D. (Dan), Sham, P.C. (Pak C.), Sklar, P. (Pamela), Clair, D.S., Weinberger, D.R. (Daniel), Wendland, A. (Annika), Werge, T.M. (Thomas), Daly, M.J. (Mark J.), Sullivan, P.F. (Patrick), and O'donovan, M.C. (Michael)
- Abstract
Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia
- Published
- 2018
- Full Text
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19. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- Author
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Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), Deary, I.J. (Ian), Davies, G. (Gail), Lam, M. (Max), Harris, S.E. (Sarah), Trampush, J.W. (Joey W.), Luciano, M. (Michelle), Hill, W.D. (W. David), Hagenaars, S. (Saskia), Ritchie, S.J. (Stuart J.), Marioni, R.E. (Riccardo), Fawns-Ritchie, C., Liewald, D.C.M. (David C. M.), Okely, J.A. (Judith A.), Ahola-Olli, A.V. (Ari V.), Barnes, C.L.K. (Catriona L. K.), Bertram, L. (Lars), Bis, J.C. (Joshua), Burdick, K.E. (Katherine E.), Christoforou, A. (Andrea), Derosse, P. (Pamela), Djurovic, S. (Srdjan), Espeseth, T. (Thomas), Giakoumaki, S. (Stella), Giddaluru, S. (Sudheer), Gustavson, D.E. (Daniel E.), Hayward, C. (Caroline), Hofer, E. (Edith), Ikram, M.A. (Arfan), Karlsson, R. (Robert), Knowles, E. (Emma), Lahti, J. (Jari), Leber, I. (Isabelle), Li, S. (Shuo), Mather, R., Melle, I. (Ingrid), Morris, D. (Derek), Oldmeadow, C. (Christopher), Palviainen, T. (Teemu), Payton, A. (Antony), Pazoki, R. (Raha), Petrovic, K. (Katja), Reynolds, C.A. (C.), Sargurupremraj, M. (Muralidharan), Scholz, M. (Markus), Smith, J.A. (Jennifer A), Smith, A.V. (Albert), Terzikhan, N. (Natalie), Thalamuthu, A. (Anbupalam), Trompet, S. (Stella), Lee, S.J. (Sven) van der, Ware, E.B. (Erin B.), Windham, B.G. (Gwen), Wright, M.J. (Margaret J.), Yang, J. (Jingyun), Yu, J. (Jin), Ames, D.J. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Andreassen, O.A. (Ole), Armstrong, N.J. (Nicola J.), Assareh, A.A., Attia, J. (John), Attix, D. (Deborah), Avramopoulos, D. (Dimitrios), Bennett, D.A. (David), Böhmer, M.R. (Marcel), Boyle, P.A. (Patricia A.), Brodaty, H. (Henry), Campbell, H. (Harry), Cannon, T.D. (Tyrone D.), Cirulli, E.T. (Elizabeth T.), Congdon, E. (Eliza), Conley, E.D. (Emily Drabant), Corley, J. (Janie), Cox, S.R. (Simon R.), Dale, A.M. (Anders), Dehghan, A. (Abbas), Dick, D. (Danielle), Dickinson, D. (Dwight), Hagen, K. (Knut), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Ford, I. (Ian), Freimer, N.A. (Nelson A.), Gao, H. (He), Giegling, I. (Ina), Gillespie, N.A. (Nathan A.), Gordon, S.D. (Scott D.), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B. (Tamara), Hartmann, A.M. (Annette M), Hatzimanolis, A. (Alex), Heiss, G. (Gerardo), Holliday, E.G. (Elizabeth), Joshi, P.K. (Peter), Kähönen, M. (Mika), Kardia, S.L.R. (Sharon L. R.), Karlsson, I. (Ida), Kleineidam, L. (Luca), Knopman, D.S. (David), Kochan, N.A. (Nicole A.), Konte, B. (Bettina), Kwok, J.B.J. (John), Le Hellard, S. (Stephanie), Lee, T. (Teresa), Lehtimäki, T. (Terho), Li, S.-C. (Shu-Chen), Liu, T. (Tian), Koini, M. (Marisa), London, E. (Edythe), Longstreth Jr, W.T., Lopez, O.L. (Oscar), Loukola, A. (Anu), Luck, T. (Tobias), Lundervold, A.J. (Astri), Lundquist, A. (Anders), Lyytikäinen, L.-P. (Leo-Pekka), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant W.), Murray, A.D. (Alison D.), Need, A.C. (Anna C.), Noordam, R. (Raymond), Nyberg, L. (Lisa), Ollier, W.E.R. (William), Papenberg, G., Pattie, A. (Alison), Polasek, O. (Ozren), Poldrack, R.A. (Russell A.), Psaty, B.M. (Bruce M.), Reppermund, S., Riedel-Heller, S. (Steffi), Rose, R.J. (Richard), Rotter, J.I. (Jerome I.), Roussos, A. (Alexandra), Rovio, S.P. (Suvi P.), Saba, Y. (Yasaman), Sabb, F.W. (Fred W.), Sachdev, P.S. (Perminder), Satizabal, C.L. (Claudia), Schmid, M. (Matthias), Scott, R.J. (Rodney J.), Scult, M.A. (Matthew A.), Simino, J. (Jeannette), Slagboom, P.E. (Eline), Smyrnis, N. (Nikolaos), Soumaré, A. (Aicha), Stefanis, N.C. (Nikos C.), Stott, D.J. (David. J.), Straub, R.E. (Richard), Sundet, K. (Kjetil), Taylor, A.M. (Adele M.), Taylor, K.D. (Kent), Tzoulaki, I., Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vitart, V. (Veronique), Voineskos, A.N. (Aristotle N.), Kaprio, J. (Jaakko), Wagner, M. (Michael), Wagner, H. (Hermann), Weinhold, L. (Leonie), Wen, K.H. (K. Hoyan), Widen, E., Yang, Q. (Qiong Fang), Zhao, W. (Wei), Adams, H.H.H. (Hieab), Arking, D.E. (Dan), Bilder, R.M. (Robert M.), Bitsios, P. (Panos), Boerwinkle, E. (Eric), Chiba-Falek, O. (Ornit), Corvin, A. (Aiden), Jager, P.L. (Philip) de, Debette, S. (Stéphanie), Donohoe, D.J. (Dennis), Elliott, P. (Paul), Fitzpatrick, A.L. (Annette), Gill, M. (Michael), Glahn, D.C. (David), Hägg, S. (Sara), Hansell, N.K. (Narelle), Hariri, A.R. (Ahmad), Ikram, M.K. (Kamran), Jukema, J.W. (Jan Wouter), Vuoksimaa, E. (Eero), Keller, M.C. (Matthew C), Kremen, W.S. (William S.), Launer, L.J. (Lenore), Lindenberger, U. (Ulman), Palotie, A. (Aarno), Pedersen, N.L. (Nancy), Pendleton, N. (Neil), Porteous, D.J. (David J.), Räikkönen, K. (Katri), Raitakari, O.T. (Olli T.), Ramirez, A. (Alfredo), Reinvang, I. (Ivar), Rudan, I. (Igor), Rujescu, D. (Dan), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Schofield, P.W. (Peter W.), Schofield, C.J. (Christopher), Starr, J.M. (John), Steen, V.M. (Vidar), Trollor, J., Turner, S.T. (Steven T.), Duijn, C.M. (Cornelia) van, Villringer, A. (Arno), Weinberger, D.R. (Daniel), Weir, D.R. (David R.), Wilson, J.F. (James F.), Malhotra, A.K. (Anil K), McIntosh, A.M. (Andrew), Gale, C.R. (Catharine R.), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Bressler, J. (Jan), Lencz, T. (Todd), and Deary, I.J. (Ian)
- 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 c
- Published
- 2018
- Full Text
- View/download PDF
20. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- Author
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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, I., 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., 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, Arno, Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., 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, I., 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., 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, Arno, Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., 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.
- Published
- 2018
21. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
- Author
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Marshall, C.R. (Christian), Howrigan, D.P. (Daniel P.), Merico, D. (Daniele), Thiruvahindrapuram, B. (Bhooma), Wu, W. (Wenting), Greer, D.S. (Douglas S.), Antaki, D. (Danny), Shetty, A. (Aniket), Holmans, P.A. (Peter A.), Pinto, D. (Duane), Gujral, M. (Madhusudan), Brandler, W.M. (William M.), Malhotra, D. (Dheeraj), Wang, Z. (Zhouzhi), Fuentes Fajarado, K.V. (Karin V.), Maile, M.S. (Michelle S.), Ripke, S. (Stephan), Agartz, I. (Ingrid), Albus, M. (Margot), Alexander, M. (Madeline), Amin, F. (Farooq), Atkins, J. (Joshua), Bacanu, S.A. (Silviu), Belliveau, R.A. (Richard A.), Bergen, S.E. (Sarah), Bertalan, M. (Marcelo), Bevilacqua, E. (Elizabeth), Bigdeli, T.B. (Tim B.), Black, D.W. (Donald), Bruggeman, R. (Richard), Buccola, N.G. (Nancy G), Buckner, M., Bulik-Sullivan, B.K. (Brendan), Byerley, W.F. (William F), Cahn, W. (Wiepke), Cai, G. (Guiqing), Cairns, M.J. (Murray J.), Campion, D. (Dominique), Cantor, R.M., Carr, V.J. (Vaughan), Carrera, N. (Noa), Catts, S.V. (Stanley), Chambert, K. (Kimberly), Cheng, W. (Wei), Cloninger, C.R. (C Robert), Cohen, D.J. (David J.), Cormican, P. (Paul), Craddock, N.J. (Nick), Crespo-Facorro, B. (Benedicto), Crowley, J.J. (James), Curtis, D. (David), Davidson, M.W. (Michael ), Davis, K.L. (Kenneth), Degenhardt, F., Del-Favero, J. (Jurgen), Delisi, L.E. (Lynn), Dikeos, D. (Dimitris), Dinan, T. (Timothy), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drapeau, E. (Elodie), Duan, J. (Jubao), Dudbridge, F. (Frank), Eichhammer, P. (Peter), Hagen, K. (Knut), Escott-Price, V. (Valentina), Essioux, L. (Laurent), Fanous, A.H. (Ayman H.), Farh, K.-H. (Kai-How), Farrell, M.S. (Martilias), Frank, J. (Josef), Franke, L. (Lude), Freedman, R. (Robert), Freimer, N.B. (Nelson), Friedman, J.I. (Joseph), Forstner, A.J. (Andreas), Fromer, M. (Menachem), Genovese, G. (Giulio), Georgieva, I. (Irina), Gershon, E.S. (Elliot S.), Giegling, I. (Ina), Giusti-Rodríguez, P. (Paola), Godard, S. (Stephanie), Goldstein, J.I. (Jacqueline), Gratten, J. (Jacob), Haan, L. (Lieuwe) de, Hamshere, M.L. (Marian), Hansen, M. (Mark), Hansen, T. (Thomas), Haroutunian, V. (Vahram), Hartmann, A.M. (Annette M), Henskens, F.A. (Frans), Herms, S. (Stefan), Hirschhorn, J.N. (Joel), Hoffmann, P. (Per), Hofman, A. (Andrea), Huang, H. (Hailiang), Ikeda, M. (Masashi), Joa, I. (Inge), Kähler, J. (Jan), Kahn, R. (René), Kalaydjieva, L. (Luba), Karjalainen, J. (Juha), Kavanagh, D. (David), Keller, M.C. (Matthew C), Kelly, B.J. (Brian J.), Kennedy, J.L., Kim, Y. (Yunjung), Knowles, J.A. (James A), Konte, B. (Bettina), Laurent, C. (Camille), Lee, P.H. (Phil), Lee, S.U. (Seung), Legge, S.E. (Sophie), Lerer, B. (Bernard), Levy, D.L. (Deborah L.), Liang, K.-Y. (Kung-Yee), Lieberman, A.P. (Andrew), Lönnqvist, J. (Jouko), Loughland, C.M. (Carmel), Magnusson, P.K. (Patrik), Maher, B.S. (Brion), Maier, W. (Wolfgang), Mallet, V. (Vincent), Mattheisen, M. (Manuel), Mattingsdal, M. (Morten), McCarley, R.W. (Robert), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Meier, S., Meijer, C. (Carin), Melle, I. (Ingrid), Mesholam-Gately, R.I. (Raquelle), Metspalu, A. (Andres), Michie, P.T. (Patricia), Milani, L. (Lili), Milanova, V. (Vihra), Mokrab, Y. (Younes), Morris, D.W. (Derek W), Müller-Myhsok, B. (B.), Murphy, K.C. (Kieran), Murray, R. (Robin), Myin-Germeys, I. (Inez), Nenadic, I. (Igor), Nertney, D.A. (Deborah), Nestadt, G. (Gerald), Nicodemus, K.K. (Kristin), Nisenbaum, L. (Laura), Nordin, A. (Annelie), O'Callaghan, E. (Eadbhard), O'Dushlaine, C. (Colm), Oh, S.-Y. (Sang-Yun), Olincy, A. (Ann), Olsen, L. (Line), O'Neill, F.A. (Francis), Os, J. (Jim) van, Pantelis, C. (Christos), Papadimitriou, G.N. (George), Parkhomenko, E. (Elena), Pato, C. (Carlos), Paunio, T. (Tiina), Perkins, D.O. (Diana O.), Pers, T.H. (Tune), Pietiläinen, O.P.H. (Olli), Pimm, J. (Jonathan), Pocklington, A.J. (Andrew), Powell, J. (John), Price, A. (Alkes), Pulver, A.E. (Ann), Purcell, S.M. (Shaun M.), Quested, D.J. (Digby J), Rasmussen, H.B. (Henrik B), Reichenberg, A. (Abraham), Reimers, B. (Bernhard), Richards, A. (Alex), Roffman, J.L. (Joshua), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Savitz, A. (Adam), Schall, J.D. (Jeffrey), Schulze, T.G. (Thomas), Schwab, S.G. (Sibylle G.), Scolnick, E. (Edward), Scott, R.J. (Rodney), Seidman, L.J. (Larry), Shi, J. (Jianxin), Silverman, J.M. (Jeremy M.), Smoller, J.W., Söderman, E. (Erik), Spencer, C.C.A. (Chris C.), Stahl, E.A. (Eli A.), Strengman, E. (Eric), Strohmaier, J., Stroup, T.S. (T. Scott), Suvisaari, J. (Jaana), Svrakic, D.M. (Dragan), Szatkiewicz, J.P. (Jin P.), Thirumalai, S. (Srinivasa), Tooney, P.A. (Paul A.), Veijola, J. (Juha), Visscher, P.M. (Peter), Waddington, J. (Joanne), Walsh, D. (Dermot), Webb, B.T. (Bradley T.), Weiser, M. (Mark), Wildenauer, D.B. (Dieter), Williams, N.M. (Nigel M.), Williams, S. (Stephanie), Witt, S.H. (Stephanie H), Wolen, A.R. (Aaron), Wormley, B.K. (Brandon K.), Wray, N.R. (Naomi), Wu, J.Q. (Jing Qin), Zai, C.C. (Clement), Adolfsson, R., Andreassen, O.A. (Ole A.), Blackwood, D.H.R. (Douglas), Bramon, E. (Elvira), Buxbaum, J.D. (Joseph D), Cichon, S. (Sven), Collier, D.A. (David), Corvin, A. (Aiden), Daly, M.J. (Mark J.), Darvasi, A. (Ariel), Domenici, E. (Enrico), Esko, T. (Tõnu), Gejman, P.V. (Pablo), Gill, M. (Michael), Gurling, H. (Hugh), Hultman, C.M. (Christina), Iwata, N. (Nakao), Jablensky, A. (Assen), Jönsson, E.G. (Erik), Kendler, K. (K.), Kirov, G. (George), Knight, J. (Jo), Levinson, D.F. (Douglas F.), Li, Q.S. (Qingqin S.), McCarroll, S.A. (Steve), McQuillin, A. (Andrew), Moran, J.L. (Jennifer L), Mowry, B.J. (Bryan J), Nöthen, M.M. (Markus), Ophoff, R.A. (Roel A.), Owen, M.J. (Michael), Palotie, A. (Aarno), Petryshen, T.L. (Tracey), Posthuma, D. (Danielle), Rietschel, M. (Marcella), Riley, B.P. (Brien P.), Rujescu, D. (Dan), Sklar, P. (Pamela), St Clair, D. (David), Walters, J.T. (James), Werge, T.M. (Thomas), Sullivan, P.F. (Patrick), O'donovan, M.C. (Michael), Scherer, S.W. (Stephen), Neale, B.M. (Benjamin), Sebat, J. (Jonathan), Marshall, C.R. (Christian), Howrigan, D.P. (Daniel P.), Merico, D. (Daniele), Thiruvahindrapuram, B. (Bhooma), Wu, W. (Wenting), Greer, D.S. (Douglas S.), Antaki, D. (Danny), Shetty, A. (Aniket), Holmans, P.A. (Peter A.), Pinto, D. (Duane), Gujral, M. (Madhusudan), Brandler, W.M. (William M.), Malhotra, D. (Dheeraj), Wang, Z. (Zhouzhi), Fuentes Fajarado, K.V. (Karin V.), Maile, M.S. (Michelle S.), Ripke, S. (Stephan), Agartz, I. (Ingrid), Albus, M. (Margot), Alexander, M. (Madeline), Amin, F. (Farooq), Atkins, J. (Joshua), Bacanu, S.A. (Silviu), Belliveau, R.A. (Richard A.), Bergen, S.E. (Sarah), Bertalan, M. (Marcelo), Bevilacqua, E. (Elizabeth), Bigdeli, T.B. (Tim B.), Black, D.W. (Donald), Bruggeman, R. (Richard), Buccola, N.G. (Nancy G), Buckner, M., Bulik-Sullivan, B.K. (Brendan), Byerley, W.F. (William F), Cahn, W. (Wiepke), Cai, G. (Guiqing), Cairns, M.J. (Murray J.), Campion, D. (Dominique), Cantor, R.M., Carr, V.J. (Vaughan), Carrera, N. (Noa), Catts, S.V. (Stanley), Chambert, K. (Kimberly), Cheng, W. (Wei), Cloninger, C.R. (C Robert), Cohen, D.J. (David J.), Cormican, P. (Paul), Craddock, N.J. (Nick), Crespo-Facorro, B. (Benedicto), Crowley, J.J. (James), Curtis, D. (David), Davidson, M.W. (Michael ), Davis, K.L. (Kenneth), Degenhardt, F., Del-Favero, J. (Jurgen), Delisi, L.E. (Lynn), Dikeos, D. (Dimitris), Dinan, T. (Timothy), Djurovic, S. (Srdjan), Donohoe, D.J. (Dennis), Drapeau, E. (Elodie), Duan, J. (Jubao), Dudbridge, F. (Frank), Eichhammer, P. (Peter), Hagen, K. (Knut), Escott-Price, V. (Valentina), Essioux, L. (Laurent), Fanous, A.H. (Ayman H.), Farh, K.-H. (Kai-How), Farrell, M.S. (Martilias), Frank, J. (Josef), Franke, L. (Lude), Freedman, R. (Robert), Freimer, N.B. (Nelson), Friedman, J.I. (Joseph), Forstner, A.J. (Andreas), Fromer, M. (Menachem), Genovese, G. (Giulio), Georgieva, I. (Irina), Gershon, E.S. (Elliot S.), Giegling, I. (Ina), Giusti-Rodríguez, P. (Paola), Godard, S. (Stephanie), Goldstein, J.I. (Jacqueline), Gratten, J. (Jacob), Haan, L. (Lieuwe) de, Hamshere, M.L. (Marian), Hansen, M. (Mark), Hansen, T. (Thomas), Haroutunian, V. (Vahram), Hartmann, A.M. (Annette M), Henskens, F.A. (Frans), Herms, S. (Stefan), Hirschhorn, J.N. (Joel), Hoffmann, P. (Per), Hofman, A. (Andrea), Huang, H. (Hailiang), Ikeda, M. (Masashi), Joa, I. (Inge), Kähler, J. (Jan), Kahn, R. (René), Kalaydjieva, L. (Luba), Karjalainen, J. (Juha), Kavanagh, D. (David), Keller, M.C. (Matthew C), Kelly, B.J. (Brian J.), Kennedy, J.L., Kim, Y. (Yunjung), Knowles, J.A. (James A), Konte, B. (Bettina), Laurent, C. (Camille), Lee, P.H. (Phil), Lee, S.U. (Seung), Legge, S.E. (Sophie), Lerer, B. (Bernard), Levy, D.L. (Deborah L.), Liang, K.-Y. (Kung-Yee), Lieberman, A.P. (Andrew), Lönnqvist, J. (Jouko), Loughland, C.M. (Carmel), Magnusson, P.K. (Patrik), Maher, B.S. (Brion), Maier, W. (Wolfgang), Mallet, V. (Vincent), Mattheisen, M. (Manuel), Mattingsdal, M. (Morten), McCarley, R.W. (Robert), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Meier, S., Meijer, C. (Carin), Melle, I. (Ingrid), Mesholam-Gately, R.I. (Raquelle), Metspalu, A. (Andres), Michie, P.T. (Patricia), Milani, L. (Lili), Milanova, V. (Vihra), Mokrab, Y. (Younes), Morris, D.W. (Derek W), Müller-Myhsok, B. (B.), Murphy, K.C. (Kieran), Murray, R. (Robin), Myin-Germeys, I. (Inez), Nenadic, I. (Igor), Nertney, D.A. (Deborah), Nestadt, G. (Gerald), Nicodemus, K.K. (Kristin), Nisenbaum, L. (Laura), Nordin, A. (Annelie), O'Callaghan, E. (Eadbhard), O'Dushlaine, C. (Colm), Oh, S.-Y. (Sang-Yun), Olincy, A. (Ann), Olsen, L. (Line), O'Neill, F.A. (Francis), Os, J. (Jim) van, Pantelis, C. (Christos), Papadimitriou, G.N. (George), Parkhomenko, E. (Elena), Pato, C. (Carlos), Paunio, T. (Tiina), Perkins, D.O. (Diana O.), Pers, T.H. (Tune), Pietiläinen, O.P.H. (Olli), Pimm, J. (Jonathan), Pocklington, A.J. (Andrew), Powell, J. (John), Price, A. (Alkes), Pulver, A.E. (Ann), Purcell, S.M. (Shaun M.), Quested, D.J. (Digby J), Rasmussen, H.B. (Henrik B), Reichenberg, A. (Abraham), Reimers, B. (Bernhard), Richards, A. (Alex), Roffman, J.L. (Joshua), Roussos, A. (Alexandra), Ruderfer, D. (Douglas), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Savitz, A. (Adam), Schall, J.D. (Jeffrey), Schulze, T.G. (Thomas), Schwab, S.G. (Sibylle G.), Scolnick, E. (Edward), Scott, R.J. (Rodney), Seidman, L.J. (Larry), Shi, J. (Jianxin), Silverman, J.M. (Jeremy M.), Smoller, J.W., Söderman, E. (Erik), Spencer, C.C.A. (Chris C.), Stahl, E.A. (Eli A.), Strengman, E. (Eric), Strohmaier, J., Stroup, T.S. (T. Scott), Suvisaari, J. (Jaana), Svrakic, D.M. (Dragan), Szatkiewicz, J.P. (Jin P.), Thirumalai, S. (Srinivasa), Tooney, P.A. (Paul A.), Veijola, J. (Juha), Visscher, P.M. (Peter), Waddington, J. (Joanne), Walsh, D. (Dermot), Webb, B.T. (Bradley T.), Weiser, M. (Mark), Wildenauer, D.B. (Dieter), Williams, N.M. (Nigel M.), Williams, S. (Stephanie), Witt, S.H. (Stephanie H), Wolen, A.R. (Aaron), Wormley, B.K. (Brandon K.), Wray, N.R. (Naomi), Wu, J.Q. (Jing Qin), Zai, C.C. (Clement), Adolfsson, R., Andreassen, O.A. (Ole A.), Blackwood, D.H.R. (Douglas), Bramon, E. (Elvira), Buxbaum, J.D. (Joseph D), Cichon, S. (Sven), Collier, D.A. (David), Corvin, A. (Aiden), Daly, M.J. (Mark J.), Darvasi, A. (Ariel), Domenici, E. (Enrico), Esko, T. (Tõnu), Gejman, P.V. (Pablo), Gill, M. (Michael), Gurling, H. (Hugh), Hultman, C.M. (Christina), Iwata, N. (Nakao), Jablensky, A. (Assen), Jönsson, E.G. (Erik), Kendler, K. (K.), Kirov, G. (George), Knight, J. (Jo), Levinson, D.F. (Douglas F.), Li, Q.S. (Qingqin S.), McCarroll, S.A. (Steve), McQuillin, A. (Andrew), Moran, J.L. (Jennifer L), Mowry, B.J. (Bryan J), Nöthen, M.M. (Markus), Ophoff, R.A. (Roel A.), Owen, M.J. (Michael), Palotie, A. (Aarno), Petryshen, T.L. (Tracey), Posthuma, D. (Danielle), Rietschel, M. (Marcella), Riley, B.P. (Brien P.), Rujescu, D. (Dan), Sklar, P. (Pamela), St Clair, D. (David), Walters, J.T. (James), Werge, T.M. (Thomas), Sullivan, P.F. (Patrick), O'donovan, M.C. (Michael), Scherer, S.W. (Stephen), Neale, B.M. (Benjamin), and Sebat, J. (Jonathan)
- Abstract
Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.
- Published
- 2017
- Full Text
- View/download PDF
22. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium
- Author
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Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., et al., Berg, S.M. van den, Moor, M.H. de, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abdellaoui, A., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G.D., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J.G., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Mbarek, H., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Nivard, M.G., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., and et al.
- Abstract
Contains fulltext : 166013.pdf (publisher's version ) (Open Access), Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
- Published
- 2016
23. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium
- Author
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Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abdellaoui, A. (Abdel), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew C.), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Mbarek, H., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Nivard, M. (Michel), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Generation Scotland, Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura J.), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Penninx, B.W.J.H. (Brenda), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy L.), Terracciano, A., McGue, M. (Matt), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abdellaoui, A. (Abdel), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew C.), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Mbarek, H., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Nivard, M. (Michel), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Generation Scotland, Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura J.), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Penninx, B.W.J.H. (Brenda), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy L.), Terracciano, A., McGue, M. (Matt), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
- Abstract
Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.
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- 2016
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24. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory
- Author
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van den Berg, S.M., de Moor, M.H.M., McGue, M., Pettersson, E., Terracciano, A., Verweij, C.J.H., Amin, N., Derringer, J., Esko, T., Grootheest, G., Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., de Geus, E.J.C., Giegling, I., Gow, A. J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkilä, K., Iacono, W.G., Janzing, J., Jokela, M, Kiemeney, L., Lehtimäki, T., Madden, P.A.F., Magnusson, P.K.E., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Pulkki-Råback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppälä, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J, Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Räikkönen, K., Arias-Vasquez, A., Costa, P.T., Keltikangas-Järvinen, L., van Duijn, C.M., Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Biological Psychology, Clinical Child and Family Studies, EMGO+ - Mental Health, Psychiatry, and EMGO - Mental health
- Subjects
Netherlands Twin Register (NTR) - Abstract
Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized. © 2014 The Author(s).
- Published
- 2014
25. Nine differentially expressed genes from a post mortem study and their association with suicidal status in a sample of suicide completers, attempters and controls
- Author
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Balestri, M., primary, Crisafulli, C., additional, Donato, L., additional, Giegling, I., additional, Calati, R., additional, Antypa, N., additional, Schneider, B., additional, Marusic, D., additional, Tarozzi, M.E., additional, Paragi, M., additional, Hartmann, A.M., additional, Konte, B., additional, Marsano, A., additional, Serretti, A., additional, and Rujescu, D., additional
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- 2016
- Full Text
- View/download PDF
26. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways.
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O'Dushlaine, C., Rossin, L., Lee, P.H., Duncan, L., Parikshak, N.N., Newhouse, S., Ripke, S., Neale, B.M., Purcell, S., Posthuma, D., Nurnberger, J.I., Lee, S.H., Faraone, S.V., Perlis, R.H., Mowry, B.J., Thapar, A., Goddard, M.E., Witte, J.S., Absher, D., Agartz, I., Akil, H., Amin, F., Andreassen, O.A., Anjorin, A., Anney, R., Anttila, V., Arking, D.E., Asherson, P., Azevedo, M.H., Backlund, L., Badner, J.A., Bailey, A.J., Banaschewski, T., Barchas, J.D., Barnes, M.R., Barrett, T.B., Bass, N., Battaglia, A., Bauer, M., Bayes, M., Bellivier, F., Bergen, S.E., Berrettini, W., Betancur, C., Bettecken, T., Biederman, J., Binder, E.B., Black, D.W., Blackwood, D.H., Bloss, C.S., Boehnke, M., Boomsma, D.I., Breuer, R., Bruggeman, R., Cormican, P., Buccola, N.G., Buitelaar, J.K., Bunney, W.E., Buxbaum, J.D., Byerley, W.F., Byrne, E.M., Caesar, S., Cahn, W., Cantor, R.M., Casas, M., Chakravarti, A., Chambert, K., Choudhury, K., Cichon, S., Mattheisen, M., Cloninger, C.R., Collier, D.A., Cook, E.H., Coon, H., Cormand, B., Corvin, A., Coryell, W.H., Craig, D.W., Craig, I., Crosbie, J., Cuccaro, M.L., Curtis, D., Czamara, D., Datta, S., Dawson, G., Day, R., Geus, E.J. de, Degenhardt, F., Djurovic, S., Donohoe, G., Doyle, A., Duan, J., Dudbridge, F., Duketis, E., Ebstein, R.P., Edenberg, H.J., Elia, J., Ennis, S., Etain, B., Fanous, A., Farmer, A., Ferrier, I.N., Flickinger, M., Foroud, T.M., Frank, J., Franke, B., Fraser, C., Freedman, R., Freimer, N.B., Freitag, C.M., Friedl, M., Frisen, L., Gallagher, L., Gejman, P.V., Georgieva, L., Gershon, E.S., Giegling, I., Gill, M., Gordon, S., Gordon-Smith, K., Green, E.K., Greenwood, T.A., Grice, D.E., Gross, M., Grozeva, D., Guan, W., Gurling, H., Haan, L. de, Haines, J.L., Hakonarson, H., Hallmayer, J., Hamilton, S.P., Hamshere, M., Hansen, T., Hartmann, A.M., Hauutzinger, M., Heath, A.C., Henders, A.K., Herms, S., Hickie, I., et al., O'Dushlaine, C., Rossin, L., Lee, P.H., Duncan, L., Parikshak, N.N., Newhouse, S., Ripke, S., Neale, B.M., Purcell, S., Posthuma, D., Nurnberger, J.I., Lee, S.H., Faraone, S.V., Perlis, R.H., Mowry, B.J., Thapar, A., Goddard, M.E., Witte, J.S., Absher, D., Agartz, I., Akil, H., Amin, F., Andreassen, O.A., Anjorin, A., Anney, R., Anttila, V., Arking, D.E., Asherson, P., Azevedo, M.H., Backlund, L., Badner, J.A., Bailey, A.J., Banaschewski, T., Barchas, J.D., Barnes, M.R., Barrett, T.B., Bass, N., Battaglia, A., Bauer, M., Bayes, M., Bellivier, F., Bergen, S.E., Berrettini, W., Betancur, C., Bettecken, T., Biederman, J., Binder, E.B., Black, D.W., Blackwood, D.H., Bloss, C.S., Boehnke, M., Boomsma, D.I., Breuer, R., Bruggeman, R., Cormican, P., Buccola, N.G., Buitelaar, J.K., Bunney, W.E., Buxbaum, J.D., Byerley, W.F., Byrne, E.M., Caesar, S., Cahn, W., Cantor, R.M., Casas, M., Chakravarti, A., Chambert, K., Choudhury, K., Cichon, S., Mattheisen, M., Cloninger, C.R., Collier, D.A., Cook, E.H., Coon, H., Cormand, B., Corvin, A., Coryell, W.H., Craig, D.W., Craig, I., Crosbie, J., Cuccaro, M.L., Curtis, D., Czamara, D., Datta, S., Dawson, G., Day, R., Geus, E.J. de, Degenhardt, F., Djurovic, S., Donohoe, G., Doyle, A., Duan, J., Dudbridge, F., Duketis, E., Ebstein, R.P., Edenberg, H.J., Elia, J., Ennis, S., Etain, B., Fanous, A., Farmer, A., Ferrier, I.N., Flickinger, M., Foroud, T.M., Frank, J., Franke, B., Fraser, C., Freedman, R., Freimer, N.B., Freitag, C.M., Friedl, M., Frisen, L., Gallagher, L., Gejman, P.V., Georgieva, L., Gershon, E.S., Giegling, I., Gill, M., Gordon, S., Gordon-Smith, K., Green, E.K., Greenwood, T.A., Grice, D.E., Gross, M., Grozeva, D., Guan, W., Gurling, H., Haan, L. de, Haines, J.L., Hakonarson, H., Hallmayer, J., Hamilton, S.P., Hamshere, M., Hansen, T., Hartmann, A.M., Hauutzinger, M., Heath, A.C., Henders, A.K., Herms, S., Hickie, I., and et al.
- Abstract
Contains fulltext : 153763pre.pdf (preprint version ) (Open Access)
- Published
- 2015
27. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder
- Author
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Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., et al., Moor, M.H. de, Berg, S.M. van den, Verweij, K.J., Krueger, R.F., Luciano, M., Arias Vasquez, A., Matteson, L.K., Derringer, J., Esko, T., Amin, N., Gordon, S.D., Hansell, N.K., Hart, A.B., Seppala, I., Huffman, J.E., Konte, B., Lahti, J., Lee (Helen Dowling Instituut), M. van der, Miller, M., Nutile, T., Tanaka, T., Teumer, A., Viktorin, A., Wedenoja, J., Abecasis, G.R., Adkins, D.E., Agrawal, A., Allik, J., Appel, K., Bigdeli, T.B., Busonero, F., Campbell, H., Costa, P.T., Smith, G., Davies, G., Wit, H. de, Ding, J., Engelhardt, B.E., Eriksson, J.G., Fedko, I.O., Ferrucci, L., Franke, B., Giegling, I., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heinonen, K., Henders, A.K., Homuth, G., Hottenga, J.J., Iacono, W.G., Janzing, J., Jokela, M., Karlsson, R., Kemp, J.P., Kirkpatrick, M.G., Latvala, A., Lehtimaki, T., Liewald, D.C., Madden, P.A., Magri, C., Magnusson, P.K., Marten, J., Maschio, A., Medland, S.E., Mihailov, E., Milaneschi, Y., Montgomery, G.W., Nauck, M., Ouwens, K.G., Palotie, A., Pettersson, E., Polasek, O., Qian, Y., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Schmidt, C.O., Slutske, W.S., Sorice, R., Starr, J.M., Pourcain, B. St, Sutin, A.R., Timpson, N.J., Trochet, H., Vermeulen, S., Vuoksimaa, E., Widen, E., Wouda, J., Wright, M.J., Zgaga, L., Porteous, D., Minelli, A., Palmer, A.A., Rujescu, D., Ciullo, M., Hayward, C., Rudan, I., and et al.
- Abstract
Contains fulltext : 153372.pdf (publisher's version ) (Closed access), IMPORTANCE: Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES: To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES: Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS: A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 x 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 x 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 x 10-12 < P < .05) and MDD (4.02 x 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE: This study identifies a novel locus for neuroticism.
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- 2015
28. Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder
- Author
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Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Moor, M.H.M. de, Berg, S.M. (Stéphanie) van den, Verweij, K.J.H. (Karin J.), Krueger, R.F., Luciano, M. (Michelle), Arias-Vásquez, A. (Alejandro), Matteson, L.K. (Lindsay), Derringer, J., Esko, T. (Tõnu), Amin, N. (Najaf), Gordon, S.D. (Scott D.), Hansell, N.K. (Narelle), Hart, A.B. (Amy B.), Seppälä, I. (Ilkka), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Lee, M. (Minyoung), Miller, M. (Mike), Nutile, T., Tanaka, T. (Toshiko), Teumer, A. (Alexander), Viktorin, A. (Alexander), Wedenoja, J. (Juho), Abecasis, G.R. (Gonçalo), Adkins, D.E. (Daniel), Agrawal, A. (Arpana), Allik, J., Appel, K. (Katja), Bigdeli, T.B. (Tim), Busonero, F., Campbell, H. (Harry), Costa, P.T. (Paul), Smith, A.V. (Davey), Davies, G. (Gail), de Wit, H. (Harriet), Ding, J. (Jun), Engelhardt, B.E. (Barbara E.), Eriksson, J.G. (Johan G.), Fedko, I. (Iryna), Ferrucci, L. (Luigi), Franke, B. (Barbara), Giegling, I. (Ina), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heinonen, K. (Kati), Henders, A.K. (Anjali), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Karlsson, R. (Robert), Kemp, J.P. (John), Kirkpatrick, M.G. (Matthew G.), Latvala, A. (Antti), Lehtimäki, T. (Terho), Liewald, D.C. (David C.), Madden, P.A. (Pamela), Magri, C. (Chiara), Magnusson, P.K.E. (Patrik K. E.), Marten, J. (Jonathan), Maschio, A., Medland, S.E. (Sarah), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Montgomery, G.W. (Grant W.), Nauck, M. (Matthias), Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pettersson, E. (Erik), Polasek, O. (Ozren), Qian, Y. (Yong), Pulkki-Råback, L. (Laura), Raitakari, O.T. (Olli T.), Realo, A. (Anu), Rose, R.J. (Richard J.), Ruggiero, D., Schmidt, C.O. (Carsten Oliver), Slutske, W.S. (Wendy), Sorice, R., Starr, J.M. (John), St Pourcain, B. (Beate), Sutin, A.R., Timpson, N.J. (Nicholas), Trochet, H. (Holly), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Wouda, J. (Jasper), Wright, M.J. (Margaret), Zgaga, L. (Lina), Porteous, D.J. (David J.), Minelli, A. (Alessandra), Palmer, A.A. (Abraham A.), Rujescu, D. (Dan), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Metspalu, A. (Andres), Kaprio, J. (Jaakko), Deary, I.J. (Ian), Räikkönen, K. (Katri), Wilson, J.F. (James F), Keltikangas-Järvinen, L. (Liisa), Bierut, L.J. (Laura), Hettema, J.M. (John M.), Grabe, H.J. (Hans Jörgen), Duijn, C.M. (Cornelia) van, Evans, D.M. (David M.), Schlessinger, D. (David), Pedersen, N.L. (Nancy), Terracciano, A., McGue, M. (Matt), Penninx, B.W.J.H. (Brenda), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
- Abstract
IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases). OBJECTIVES To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63 661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15%of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12 < P <.05) and MDD (4.02 × 10-9 < P < .05) in the 2 other cohorts. CONCLUSIONS AND RELEVANCE This study identi
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- 2015
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29. Identification of risk loci with shared effects on five major psychiatric disorders:a genome-wide analysis
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Smoller, J.W., Ripke, S., Lee, P.H., Neale, B., Nurnberger, J.I., Santangelo, S., Sullivan, P.F., Perlis, R.H., Purcell, S.M., Fanous, A., Neale, M.C., Rietschel, M., Schulze, T.G., Thapar, A., Anney, R., Buitelaar, J.K., Farone, S.V., Hoogendijk, W.J.G., Levinson, D.F., Lesch, K.P., Riley, B., Schachar, R., Sonuga-Barke, E.J., Absher, D., Agartz, I., Akil, H., Amin, F., Andreassen, O.A., Anjorin, A., Arking, D., Asherson, P., Azevedo, M.H., Backlund, L., Badner, J.A., Banaschewski, T., Barchas, J.D., Barnes, M.R., Bass, N., Bauer, M.C.R., Bellivier, F., Bergen, S.E., Berrettini, W., Bettecken, T., Biederman, J, Binder, E.B., Black, D.W., Blackwood, D.H., Bloss, C.S., Boehnke, M., Boomsma, D.I., Breen, G., Breuer, R., Buccola, N.G., Bunner, W.E., Burmeister, M., Buxbaum, J.D., Byerley, W. F., Sian, C., Cantor, R.M., Chakravarti, A., Chambert, K., Chicon, S., Cloniger, C.R., Collier, D.A., Cook, E., Coon, H., Corvin, A., Coryell, W.H., Craig, D.W., Craig, I.W., Curtis, D., Czamara, D., Daly, M., Datta, S., Day, R., de Geus, E.J.C., Degenhardt, F., Devlin, B., Srdjan, D., Doyle, A.E., Duan, J., Dudbridge, F., Edenberg, H.J., Elkin, A., Etain, B., Farmer, A.E., Ferreira, M.A.R., Ferrier, I.N., Flickinger, M., Foroud, T., Frank, J., Franke, B., Fraser, C., Freedman, R., Freimer, N.B., Friedl, M., Frisén, L., Gejman, P.V., Georgieva, L., Gershon, E.S., Giegling, I., Gill, M., Gordon, S.D., Gordon-Smith, K., Green, E.K., Greenwood, T.A., Gross, M., Grozeva, D., Guan, W., Gurling, H., Gustafsson, O., Hakonarson, H., Hamilton, S.P., Hamshere, M.L., Hansen, T.F., Hartmann, A.M., Hautzinger, M., Heath, A.C., Henders, A.K., Herms, S., Hickie, I.B., Hipolito, M., Hoefels, S., Holmans, P.A., Holsboer, F., Hottenga, J.J., Hultman, C. M., Ingason, A., Ising, M., Jamain, S., Jones, E.G., Jones, L., Jones, I., Jung-Ying, T., Kahler, A., Kandaswamy, R., Keller, M.C., Kelsoe, J., Kennedy, J.L., Kenny, E., Kim, Y., Kirov, G. K., Knowles, J.A., Kohli, M.A., Koller, D.L., Konte, B., Korszun, A., Krasucki, R., Kuntsi, J., Phoenix, K., Landén, M., Langstrom, N., Lathrop, M., Lawrence, J., Lawson, W.B., Leboyer, M., Lencz, T., Lewis, C.M., Li, J., Lichtenstein, P., Lieberman, J. A., Lin, D., Liu, C., Lohoff, F.W., Loo, S.K., Lucae, S., MacIntyre, D.J., Madden, P.A.F., Magnusson, P., Mahon, P.B., Maier, W., Malhotra, A.K., Mattheisen, M., Matthews, K., Mattingsdal, M., McCarroll, S., McGhee, K.A., McGough, J.J., McGrath, P.J., McGuffin, P., McInnis, M.G., McIntosh, A., McKinney, R., McClean, A.W., McMahon, F.J., McQuillin, A., Medeiros, H., Medland, S.E., Meier, S., Melle, I., Meng, F., Middeldorp, C.M., Middleton, L., Vihra, M., Mitchell, P.B., Montgomery, G.W., Moran, J., Morken, G., Morris, D.W., Moskvina, V., Mowry, B. J., Muglia, P., Mühleisen, T.W., Muir, W.J., Müller-Myhsok, B., Myers, R.M., Nelson, S.F., Nievergelt, C.M., Nikolovq, I., Nimgaonkar, V.L., Nolen, W.A., Nöthen, M.M., Nwulia, E.A., Nyholt, DR, O'Donovan, M.C., O'Dushlaine, C., Oades, R.D., Olincy, A., Olsen, L., Ophoff, R.A., Osby, U., Óskarsson, H., Owen, M.J., Palotie, A., Pato, M.T., Pato, C.N., Penninx, B.W.J.H., Pergadia, M.L., Petursson, H., Pickard, B.S., Pimm, J., Piven, J., Porgeirsson, P., Posthuma, D., Potash, J.B., Propping, J., Puri, V., Quested, D., Quinn, E.M., Rasmussen, H.B., Raychaudhuri, S., Rehnström, K., Reif, A., Rice, J., Rossin, L., Rothenberger, A., Rouleau, G., Ruderfer, D., Rujescu, D., Sanders, A.R., Schalling, M., Schatzberg, A.F., Scheftner, W.A., Schellenberg, G.D., Schofield, P.R., Schork, N.J., Schumacher, J., Schwarz, M.M., Scolnick, E., Scott, L.J., Shi, J., Shillling, P.D., Shyn, S.I., Sigurdsson, E., Silverman, J.M., Sklar, P., Slager, S.L., Smalley, S.L., Smit, J.H., Smith, E.N., Sonuga-Barke, E., St Clair, D., State, M., Stefansson, K., Stefansson, H., Steffans, M., Steinberg, S., Steinhausen, H.C., Strauss, J., Strohmaier, J., Stroup, T.S., Sutcliffe, J., Szatmari, P., Szelinger, S., Thirumalai, S., Thompson, R.C., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E.J., Grootheest, G., Vieland, V., Vincent, J.B., Visscher, P.M., Watson, S.J., Weissman, M.M., Werge, T., Wienker, T.F., Willemsen, G., Williamson, R., Witt, S.H., Wray, N.R., Wright, A., Xu, W., Young, A.H., Zammit, S., Zandi, P.P., Zhang, P., Zitman, F.G., Zöllner, S., Kendler, K.S., Psychiatry, Human genetics, Epidemiology and Data Science, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, RS: CARIM School for Cardiovascular Diseases, RS: MHeNs School for Mental Health and Neuroscience, Oades, Robert D. (Beitragende*r), and Oades, Robert D.
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Netherlands Twin Register (NTR) ,Adult ,medicine.medical_specialty ,Bipolar Disorder ,Calcium Channels, L-Type ,Population ,Medizin ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Article ,Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3] ,medicine ,ddc:61 ,Attention deficit hyperactivity disorder ,Humans ,DCN PAC - Perception action and control NCEBP 9 - Mental health ,ddc:610 ,Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters ,Bipolar disorder ,Age of Onset ,Psychiatry ,education ,Child ,Genetics ,education.field_of_study ,Depressive Disorder, Major ,General Medicine ,Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3] ,medicine.disease ,Logistic Models ,Autism spectrum disorder ,Schizophrenia ,Attention Deficit Disorder with Hyperactivity ,Child Development Disorders, Pervasive ,Genetic Loci ,Expression quantitative trait loci ,Major depressive disorder ,Genome-Wide Association Study - Abstract
Item does not contain fulltext BACKGROUND: Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. METHODS: We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33,332 cases and 27,888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. FINDINGS: SNPs at four loci surpassed the cutoff for genome-wide significance (p
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- 2013
30. Genome-wide association study identifies five new schizophrenia loci
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Ripke, S. Sanders, A.R. Kendler, K.S. Levinson, D.F. Sklar, P. Holmans, P.A. Lin, D.-Y. Duan, J. Ophoff, R.A. Andreassen, O.A. Scolnick, E. Cichon, S. St. Clair, D. Corvin, A. Gurling, H. Werge, T. Rujescu, D. Blackwood, D.H.R. Pato, C.N. Malhotra, A.K. Purcell, S. Dudbridge, F. Neale, B.M. Rossin, L. Visscher, P.M. Posthuma, D. Ruderfer, D.M. Fanous, A. Stefansson, H. Steinberg, S. Mowry, B.J. Golimbet, V. De Hert, M. Jönsson, E.G. Bitter, I. Pietiläinen, O.P.H. Collier, D.A. Tosato, S. Agartz, I. Albus, M. Alexander, M. Amdur, R.L. Amin, F. Bass, N. Bergen, S.E. Black, D.W. Børglum, A.D. Brown, M.A. Bruggeman, R. Buccola, N.G. Byerley, W.F. Cahn, W. Cantor, R.M. Carr, V.J. Catts, S.V. Choudhury, K. Cloninger, C.R. Cormican, P. Craddock, N. Danoy, P.A. Datta, S. De Haan, L. Demontis, D. Dikeos, D. Djurovic, S. Donnelly, P. Donohoe, G. Duong, L. Dwyer, S. Fink-Jensen, A. Freedman, R. Freimer, N.B. Friedl, M. Georgieva, L. Giegling, I. Gill, M. Glenthøj, B. Godard, S. Hamshere, M. Hansen, M. Hansen, T. Hartmann, A.M. Henskens, F.A. Hougaard, D.M. Hultman, C.M. Ingason, A. Jablensky, A.V. Jakobsen, K.D. Jay, M. Jürgens, G. Kahn, R.S. Keller, M.C. Kenis, G. Kenny, E. Kim, Y. Kirov, G.K. Konnerth, H. Konte, B. Krabbendam, L. Krasucki, R. Lasseter, V.K. Laurent, C. Lawrence, J. Lencz, T. Lerer, F.B. Liang, K.-Y. Lichtenstein, P. Lieberman, J.A. Linszen, D.H. Lönnqvist, J. Loughland, C.M. MacLean, A.W. Maher, B.S. Maier, W. Mallet, J. Malloy, P. Mattheisen, M. Mattingsdal, M. McGhee, K.A. McGrath, J.J. McIntosh, A. McLean, D.E. McQuillin, A. Melle, I. Michie, P.T. Milanova, V. Morris, D.W. Mors, O. Mortensen, P.B. Moskvina, V. Muglia, P. Myin-Germeys, I. Nertney, D.A. Nestadt, G. Nielsen, J. Nikolov, I. Nordentoft, M. Norton, N. Nöthen, M.M. O'Dushlaine, C.T. Olincy, A. Olsen, L. O'Neill, F.A. Ørntoft, T.F. Owen, M.J. Pantelis, C. Papadimitriou, G. Pato, M.T. Peltonen, L. Petursson, H. Pickard, B. Pimm, J. Pulver, A.E. Puri, V. Quested, D. Quinn, E.M. Rasmussen, H.B. Réthelyi, J.M. Ribble, R. Rietschel, M. Riley, B.P. Ruggeri, M. Schall, U. Schulze, T.G. Schwab, S.G. Scott, R.J. Shi, J. Sigurdsson, E. Silverman, J.M. Spencer, C.C.A. Stefansson, K. Strange, A. Strengman, E. Stroup, T.S. Suvisaari, J. Terenius, L. Thirumalai, S. Thygesen, J.H. Timm, S. Toncheva, D. Van Den Oord, E. Van Os, J. Van Winkel, R. Veldink, J. Walsh, D. Wang, A.G. Wiersma, D. Wildenauer, D.B. Williams, H.J. Williams, N.M. Wormley, B. Zammit, S. Sullivan, P.F. O'Donovan, M.C. Daly, M.J. Gejman, P.V.
- Abstract
We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10 -11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9). © 2011 Nature America, Inc. All rights reserved.
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- 2011
31. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory
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Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., Boomsma, D.I., Berg, S.M. van den, Moor, M.H. de, McGue, M., Pettersson, E., Terracciano, A., Verweij, K.J., Amin, N., Derringer, J., Esko, T., Grootheest, G. van, Hansell, N.K., Huffman, J., Konte, B., Lahti, J., Luciano, M., Matteson, L.K., Viktorin, A., Wouda, J., Agrawal, A., Allik, J., Bierut, L.J., Broms, U., Campbell, H., Smith, G.D., Eriksson, J.G., Ferrucci, L., Franke, B., Fox, J.P., Geus, E.J. de, Giegling, I., Gow, A.J., Grucza, R.A., Hartmann, A.M., Heath, A.C., Heikkila, K., Iacono, W.G., Janzing, J.G., Jokela, M., Kiemeney, B., Lehtimaki, T., Madden, P.A.F., Magnusson, P.K., Northstone, K., Nutile, T., Ouwens, K.G., Palotie, A., Pattie, A., Pesonen, A.K., Polasek, O., Pulkkinen, L., Pulkki-Raback, L., Raitakari, O.T., Realo, A., Rose, R.J., Ruggiero, D., Seppala, I., Slutske, W.S., Smyth, D.C., Sorice, R., Starr, J.M., Sutin, A.R., Tanaka, T., Verhagen, J., Vermeulen, S., Vuoksimaa, E., Widen, E., Willemsen, G., Wright, M.J., Zgaga, L., Rujescu, D., Metspalu, A., Wilson, J.F., Ciullo, M., Hayward, C., Rudan, I., Deary, I.J., Raikkonen, K., Arias Vasquez, A., Costa, P.T., Keltikangas-Jarvinen, L., Duijn, C.M. van, Penninx, B.W.J.H., Krueger, R.F., Evans, D.M., Kaprio, J., Pedersen, N.L., Martin, N.G., and Boomsma, D.I.
- Abstract
Contains fulltext : 135909.pdf (publisher's version ) (Open Access), Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
- Published
- 2014
32. Harmonization of neuroticism and extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: An application of item response theory
- Author
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Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), Boomsma, D.I. (Dorret), Berg, S.M. (Stéphanie) van den, Moor, M.H.M. de, McGue, M. (Matt), Pettersson, E. (Erik), Terracciano, A., Verweij, K.J.H. (Karin J.), Amin, N. (Najaf), Derringer, J., Esko, T. (Tõnu), Grootheest, G. (Gerard) van, Hansell, N.K. (Narelle), Huffman, J.E. (Jennifer), Konte, B., Lahti, J. (Jari), Luciano, M. (Michelle), Matteson, L.K. (Lindsay), Viktorin, A. (Alexander), Wouda, J. (Jasper), Agrawal, A. (Arpana), Allik, J., Bierut, L.J. (Laura), Broms, U. (Ulla), Campbell, H. (Harry), Smith, G.D. (George Davey), Hagen, K. (Knut), Ferrucci, L. (Luigi), Franke, B. (Barbara), Fox, J.P. (Jean-Paul), Geus, E.J.C. (Eco) de, Giegling, I. (Ina), Gow, A.J. (Alan J.), Grucza, R., Hartmann, A.M. (Annette M), Heath, A.C. (Andrew), Heikkilä, K. (Kauko), Iacono, W.G. (William), Janzing, J.G.E. (Joost), Jokela, M. (Markus), Kiemeney, L.A.L.M. (Bart), Lehtimäki, T. (Terho), Madden, P.A.F. (Pamela), Magnusson, P.K. (Patrik), Northstone, K. (Kate), Nutile, T., Ouwens, K.G. (Klaasjan), Palotie, A. (Aarno), Pattie, A. (Alison), Pesonen, A.-K. (Anu-Katriina), Polasek, O. (Ozren), Pulkkinen, L. (Lea), Pulkki-Råback, L. (Laura), Raitakari, O. (Olli), Realo, A. (Anu), Rose, R.J. (Richard), Ruggiero, D., Seppälä, I. (Ilkka), Slutske, W.S. (Wendy), Smyth, D.C. (David), Sorice, R., Starr, J.M. (John), Sutin, A.R., Tanaka, T. (Toshiko), Verhagen, J. (Josine), Vermeulen, S.H.H.M. (Sita), Vuoksimaa, E. (Eero), Widen, E. (Elisabeth), Willemsen, G.A.H.M. (Gonneke), Wright, M.J. (Margaret), Zgaga, L. (Lina), Rujescu, D. (Dan), Metspalu, A. (Andres), Wilson, J.F. (James F), Ciullo, M., Hayward, C. (Caroline), Rudan, I. (Igor), Deary, I.J. (Ian), Räikkönen, K. (Katri), Arias-Vásquez, A. (Alejandro), Costa, P.T. (Paul), Keltikangas-Järvinen, L. (Liisa), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Krueger, R.F., Evans, D.M. (David), Kaprio, J. (Jaakko), Pedersen, N.L. (Nancy), Martin, N.G. (Nicholas), and Boomsma, D.I. (Dorret)
- Abstract
Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
- Published
- 2014
- Full Text
- View/download PDF
33. Genome-wide association uncovers shared genetic effects among personality traits and mood states.
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Luciano, M., Huffman, J.E., Arias Vasquez, A., Vinkhuyzen, A.A.E., Middeldorp, C.M., Giegling, I., Payton, A., Davies, G., Zgaga, L., Janzing, J.G.E., Ke, X., Galesloot, T.E., Hartmann, A.M., Ollier, W., Tenesa, A., Hayward, C., Verhagen, M., Montgomery, G.W., Hottenga, J.J., Konte, B., Starr, J.M., Vitart, V., Vos, P.E., Madden, P.A.F., Willemsen, G., Konnerth, H., Horan, M.A., Porteous, D.J., Campbell, H., Vermeulen, S., Heath, A.C., Wright, A., Polasek, O., Kovacevic, S.B., Hastie, N.D., Franke, B., Boomsma, D.I., Martin, N.G., Rujescu, D., Wilson, J.F., Buitelaar, J.K., Pendleton, N., Rudan, I., Deary, I.J., Luciano, M., Huffman, J.E., Arias Vasquez, A., Vinkhuyzen, A.A.E., Middeldorp, C.M., Giegling, I., Payton, A., Davies, G., Zgaga, L., Janzing, J.G.E., Ke, X., Galesloot, T.E., Hartmann, A.M., Ollier, W., Tenesa, A., Hayward, C., Verhagen, M., Montgomery, G.W., Hottenga, J.J., Konte, B., Starr, J.M., Vitart, V., Vos, P.E., Madden, P.A.F., Willemsen, G., Konnerth, H., Horan, M.A., Porteous, D.J., Campbell, H., Vermeulen, S., Heath, A.C., Wright, A., Polasek, O., Kovacevic, S.B., Hastie, N.D., Franke, B., Boomsma, D.I., Martin, N.G., Rujescu, D., Wilson, J.F., Buitelaar, J.K., Pendleton, N., Rudan, I., and Deary, I.J.
- Abstract
1 september 2012, Item does not contain fulltext, Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP ( approximately 2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n = 527-6,032). Suggestive association (P = 8 x 10(-8) ) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 x 10(-6) ) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P < 0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits. (c) 2012 Wiley Periodicals, Inc.
- Published
- 2012
34. P.1.a.009 - Nine differentially expressed genes from a post mortem study and their association with suicidal status in a sample of suicide completers, attempters and controls
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Balestri, M., Crisafulli, C., Donato, L., Giegling, I., Calati, R., Antypa, N., Schneider, B., Marusic, D., Tarozzi, M.E., Paragi, M., Hartmann, A.M., Konte, B., Marsano, A., Serretti, A., and Rujescu, D.
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- 2016
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35. Disruption of the neurexin 1 gene is associated with schizophrenia.
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Rujescu, D., Ingason, A., Cichon, S., Pietilainen, O.P.H., Barnes, M.R., Toulopoulou, T., Picchioni, M., Vassos, E., Ettinger, U., Bramon, E., Murray, R., Ruggeri, M., Tosato, S., Bonetto, C., Steinberg, S., Sigurdsson, E., Sigmundsson, T., Petursson, H., Gylfason, A, Olason, P., Hardarsson, G., Jonsdottir, G.A., Gustafsson, O., Fossdal, R., Giegling, I., Moller, H.J., Hartmann, A.M., Hoffmann, P., Crombie, C., Fraser, G., Walker, N., Lonnqvist, J., Suvisaari, J., Tuulio-Henriksson, A., Djurovic, S., Melle, I., Andreassen, O.A., Hansen, T., Werge, T., Kiemeney, L.A.L.M., Franke, B., Veltman, J.A., Buizer-Voskamp, J.E., Sabatti, C., Ophoff, R.A., Rietschel, M., Nothen, Markus, Stefansson, K., Peltonen, L., St Clair, D., Stefansson, H., Collier, D.A., Rujescu, D., Ingason, A., Cichon, S., Pietilainen, O.P.H., Barnes, M.R., Toulopoulou, T., Picchioni, M., Vassos, E., Ettinger, U., Bramon, E., Murray, R., Ruggeri, M., Tosato, S., Bonetto, C., Steinberg, S., Sigurdsson, E., Sigmundsson, T., Petursson, H., Gylfason, A, Olason, P., Hardarsson, G., Jonsdottir, G.A., Gustafsson, O., Fossdal, R., Giegling, I., Moller, H.J., Hartmann, A.M., Hoffmann, P., Crombie, C., Fraser, G., Walker, N., Lonnqvist, J., Suvisaari, J., Tuulio-Henriksson, A., Djurovic, S., Melle, I., Andreassen, O.A., Hansen, T., Werge, T., Kiemeney, L.A.L.M., Franke, B., Veltman, J.A., Buizer-Voskamp, J.E., Sabatti, C., Ophoff, R.A., Rietschel, M., Nothen, Markus, Stefansson, K., Peltonen, L., St Clair, D., Stefansson, H., and Collier, D.A.
- Abstract
Contains fulltext : 80670.pdf (publisher's version ) (Closed access), Deletions within the neurexin 1 gene (NRXN1; 2p16.3) are associated with autism and have also been reported in two families with schizophrenia. We examined NRXN1, and the closely related NRXN2 and NRXN3 genes, for copy number variants (CNVs) in 2977 schizophrenia patients and 33 746 controls from seven European populations (Iceland, Finland, Norway, Germany, The Netherlands, Italy and UK) using microarray data. We found 66 deletions and 5 duplications in NRXN1, including a de novo deletion: 12 deletions and 2 duplications occurred in schizophrenia cases (0.47%) compared to 49 and 3 (0.15%) in controls. There was no common breakpoint and the CNVs varied from 18 to 420 kb. No CNVs were found in NRXN2 or NRXN3. We performed a Cochran-Mantel-Haenszel exact test to estimate association between all CNVs and schizophrenia (P = 0.13; OR = 1.73; 95% CI 0.81-3.50). Because the penetrance of NRXN1 CNVs may vary according to the level of functional impact on the gene, we next restricted the association analysis to CNVs that disrupt exons (0.24% of cases and 0.015% of controls). These were significantly associated with a high odds ratio (P = 0.0027; OR 8.97, 95% CI 1.8-51.9). We conclude that NRXN1 deletions affecting exons confer risk of schizophrenia.
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- 2009
36. Neuropsychological effects of theCSMD1genome-wide associated schizophrenia risk variant rs10503253
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Donohoe, G., primary, Walters, J., additional, Hargreaves, A., additional, Rose, E.J., additional, Morris, D.W., additional, Fahey, C., additional, Bellini, S., additional, Cummins, E., additional, Giegling, I., additional, Hartmann, A.M., additional, Möller, H.-J., additional, Muglia, P., additional, Owen, M.J., additional, Gill, M., additional, O'Donovan, M.C., additional, Tropea, D., additional, Rujescu, D., additional, and Corvin, A., additional
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- 2013
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37. P.3.c.044 Influence of ANKK1 and DRD2 gene polymorphisms in response to haloperidol
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Porcelli, S., primary, Giegling, I., additional, Balzarro, B., additional, Schäfer, M., additional, Hartmann, A.M., additional, Friedl, M., additional, Möller, H.J., additional, De Ronchi, D., additional, Rujescu, D., additional, and Serretti, A., additional
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- 2012
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38. P.1.005 Glutamatergic gene variants impact the side effects and antipsychotic efficacy of haloperidol
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Drago, A., primary, Giegling, I., additional, Schäfer, M., additional, Hartmann, A.M., additional, Sander, T., additional, Toliat, M.R., additional, Moller, H.J., additional, Stassen, H.H., additional, Rujescu, D., additional, and Serretti, A., additional
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- 2010
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39. Association of a variant in the muscarinic acetylcholine receptor 2 gene (CHRM2) with nicotine addiction
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Mobascher, A., primary, Rujescu, D., additional, Mittelstraß, K., additional, Giegling, I., additional, Lamina, C., additional, Nitz, B., additional, Brenner, H., additional, Fehr, C., additional, Breitling, L.P., additional, Gallinat, J., additional, Rothenbacher, D., additional, Raum, E., additional, Müller, H., additional, Ruppert, A., additional, Hartmann, A.M., additional, Möller, H.J., additional, Gal, A., additional, Gieger, Ch., additional, Wichmann, H.E., additional, Illig, T., additional, Dahmen, N., additional, and Winterer, G., additional
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- 2010
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40. S28-03 - Pharmacogenetics of Therapy Response in Schizophrenia
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Spellmann, I., primary, Rujescu, D., additional, Musil, R., additional, Mayr, A., additional, Giegling, I., additional, Genius, J., additional, Zill, P., additional, Dehning, S., additional, Hartmann, A.M., additional, Bondy, B., additional, Müller, N., additional, Möller, H.-J., additional, and Riedel, M., additional
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- 2010
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41. Serotonin receptor 1a, 2a, 2c and CONT SNPs and personality traits in suicide attempters and controls
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Calati, R., primary, Serretti, A., additional, Giegling, I., additional, Hartmann, A.M., additional, Möller, H.J., additional, Colombo, C., additional, and Rujescu, D., additional
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- 2008
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42. 174 – Genomic findings in schizophrenia, animal models and intermediate phenotypes
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Rujescu, D., primary, Giegling, I., additional, Hartmann, A.M., additional, Genius, J., additional, Mulert, C., additional, Hegerl, U., additional, Ruppert, A., additional, Grunze, H., additional, Francks, C., additional, Muglia, P., additional, and Möller, H.J., additional
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- 2008
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43. GRIN1 locus may modify the susceptibility to seizures during alcohol withdrawal
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Rujescu, D., primary, Soyka, M., additional, Dahmen, N., additional, Preuß, U., additional, Hartmann, A.M., additional, Giegling, I., additional, Koller, G., additional, Bondy, B., additional, Möller, H.-J., additional, and Szegedi, A., additional
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- 2005
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44. S.07.04 Towards pharmacogenomics: A large-scale association study on response to haloperidol
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Rujescu, D., primary, Giegling, I., additional, Schafer, M., additional, Dahmen, N., additional, Sander, T., additional, Szegedi, A., additional, Toliat, M.R., additional, Möller, H.-J., additional, Bondy, B., additional, Hartmann, A.M., additional, and Stassen, H.H., additional
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- 2003
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45. Neuropsychological effects of the CSMD1 genome-wide associated schizophrenia risk variant rs10503253.
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Donohoe, G., Walters, J., Hargreaves, A., Rose, E.J., Morris, D.W., Fahey, C., Bellini, S., Cummins, E., Giegling, I., Hartmann, A.M., Möller, H.‐J., Muglia, P., Owen, M.J., Gill, M., O'Donovan, M.C., Tropea, D., Rujescu, D., and Corvin, A.
- Subjects
NEUROPSYCHOLOGY ,SCHIZOPHRENIA ,SINGLE nucleotide polymorphisms ,PHENOTYPES ,GERMANS ,BRAIN anatomy ,SHORT-term memory ,DISEASES - Abstract
The single-nucleotide polymorphism (SNP) rs10503253, located within the CUB and Sushi multiple domains-1 ( CSMD1) gene on 8p23.2, was recently identified as genome-wide significant for schizophrenia (SZ), but is of unknown function. We investigated the neurocognitive effects of this CSMD1 variant in vivo in patients and healthy participants using behavioral and imaging measures of brain structure and function. We compared carriers and non-carriers of the risk 'A' allele on measures of neuropsychological performance typically impaired in SZ (general cognitive ability, episodic and working memory and attentional control) in independent samples of Irish patients ( n = 387) and controls ( n = 171) and German patients (205) and controls ( n = 533). Across these groups, the risk 'A' allele at CSMD1 was associated with deleterious effects across a number of neurocognitive phenotypes. Specifically, the risk allele was associated with poorer performance on neuropsychological measures of general cognitive ability and memory function but not attentional control. These effects, while significant, were subtle, and varied between samples. Consistent with previous evidence suggesting that CSMD1 may be involved in brain mechanisms related to memory and learning, these data appear to reflect the deleterious effects of the identified 'A' risk allele on neurocognitive function, possibly as part of the mechanism by which CSMD1 is associated with SZ risk. [ABSTRACT FROM AUTHOR]
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- 2013
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46. The in vivo minigene approach to analyze tissue-specific splicing
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Stoss, O., Stoilov, P., Hartmann, A.M., Nayler, O., and Stamm, S.
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- 1999
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47. Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia
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Pardiñas, Antonio F., Smart, Sophie E., Corvin, Aiden, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph I., Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Gershon, Elliot S., Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Fanous, Ayman H., Goldstein, Jacqueline I., Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, Haan, Lieuwe de, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Frank, Josef, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V., Hougaard, David M., Ikeda, Masashi, Joa, Inge, Kelly, Brian, Julià, Antonio, Kahn, René S., Kalaydjieva, Luba, Karachanak-Yankova, Sena, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C., Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, McQuillin, Andrew, Klovins, Janis, Knowles, James A., Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Kähler, Anna K., Laurent, Claudine, Keong, Jimmy Lee Chee, Lee, S. Hong, Melle, Ingrid, Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung-Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lönnqvist, Jouko, Macek, Milan, Mortensen, Preben B., Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, Mattheisen, Manuel, Mattingsdal, Morten, McCarley, Robert W., McDonald, Colm, McIntosh, Andrew M., Mowry, Bryan J., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mokrab, Younes, Pato, Carlos N., Morris, Derek W., Mors, Ole, Murphy, Kieran C., Myin-Germeys, Inez, Müller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Periyasamy, Sathish, Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, O’Callaghan, Eadbhard, O’Dushlaine, Colm, O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Olsen, Line, Os, Jim Van, Willcocks, Isabella R., Rietschel, Marcella, Pantelis, Christos, Papadimitriou, George N., Papiol, Sergi, Parkhomenko, Elena, Pato, Michele T., Paunio, Tiina, Pejovic-Milovancevic, Milica, Perkins, Diana O., Pietiläinen, Olli, Pimm, Jonathan, Rujescu, Dan, Pocklington, Andrew J., Powell, John, Price, Alkes, Pulver, Ann E., Purcell, Shaun M., Quested, Digby, Rasmussen, Henrik B., Reichenberg, Abraham, Reimers, Mark A., Richards, Alexander L., Simonsen, Carmen, Roffman, Joshua L., Roussos, Panos, Ruderfer, Douglas M., Salomaa, Veikko, Sanders, Alan R., Schall, Ulrich, Schubert, Christian R., Schulze, Thomas G., Schwab, Sibylle G., Scolnick, Edward M., St Clair, David, Scott, Rodney J., Seidman, Larry J., Shi, Jianxin, Sigurdsson, Engilbert, Silagadze, Teimuraz, Silverman, Jeremy M., Sim, Kang, Slominsky, Petr, Smoller, Jordan W., So, Hon-Cheong, Tooney, Paul, Spencer, Chris C. A., Stahl, Eli A., Stefansson, Hreinn, Steinberg, Stacy, Stogmann, Elisabeth, Straub, Richard E., Strengman, Eric, Strohmaier, Jana, Stroup, T. Scott, Subramaniam, Mythily, Wu, Jing Qin, Suvisaari, Jaana, Svrakic, Dragan M., Szatkiewicz, Jin P., Söderman, Erik, Thirumalai, Srinivas, Toncheva, Draga, Tosato, Sarah, Veijola, Juha, Waddington, John, Walsh, Dermot, Andreassen, Ole A., Wang, Dai, Wang, Qiang, Webb, Bradley T., Weiser, Mark, Wildenauer, Dieter B., Williams, Nigel M., Williams, Stephanie, Witt, Stephanie H., Wolen, Aaron R., Wong, Emily H. M., Kowalec, Kaarina, Wormley, Brandon K., Xi, Hualin Simon, Zai, Clement C., Zheng, Xuebin, Zimprich, Fritz, Wray, Naomi R., Stefansson, Kari, Visscher, Peter M., Adolfsson, Rolf, Blackwood, Douglas H. R., Sullivan, Patrick F., Bramon, Elvira, Buxbaum, Joseph D., Børglum, Anders D., Cichon, Sven, Darvasi, Ariel, Domenici, Enrico, Ehrenreich, Hannelore, Esko, Tõnu, Gejman, Pablo V., Gill, Michael, Murray, Robin M., Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen V., Jönsson, Erik G., Kendler, Kenneth S., Kirov, George, Knight, Jo, Lencz, Todd, Levinson, Douglas F., Holmans, Peter A., Owen, Michael J., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., McCarroll, Steven A., Moran, Jennifer L., Nöthen, Markus M., Ophoff, Roel A., Palotie, Aarno, Petryshen, Tracey L., MacCabe, James H., Posthuma, Danielle, Riley, Brien P., Sham, Pak C., Sklar, Pamela, Clair, David St, Weinberger, Daniel R., Wendland, Jens R., Werge, Thomas, Daly, Mark J., Agbedjro, Deborah, O’Donovan, Michael C., Stahl, Daniel, Kapur, Shitij, Millgate, Edward, Kepinska, Adrianna, Kravariti, Eugenia, Ajnakina, Olesya, Alameda, Luis, Barnes, Thomas R. E., Berardi, Domenico, Bonora, Elena, Walters, James T. R., Camporesi, Sara, Cleusix, Martine, Conus, Philippe, Crespo-Facorro, Benedicto, D’Andrea, Giuseppe, Demjaha, Arsime, Do, Kim Q., Doody, Gillian A., Eap, Chin B., Ferchiou, Aziz, Ripke, Stephan, Di Forti, Marta, Guidi, Lorenzo, Homman, Lina, Jenni, Raoul, Joyce, Eileen M., Kassoumeri, Laura, Khadimallah, Inès, Lastrina, Ornella, Muratori, Roberto, Noyan, Handan, Neale, Benjamin M., O’Neill, Francis A., Pignon, Baptiste, Restellini, Romeo, Richard, Jean-Romain, Schürhoff, Franck, Španiel, Filip, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Üçok, Alp, Farh, Kai-How, Vázquez-Bourgon, Javier, Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Dennison, Charlotte A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard A ., Lynham, Amy J., Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Legge, Sophie E., Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberly D., Chan, Raymond C. K., Chen, Ronald Y. L., Chen, Eric Y. H., Cheng, Wei, Baune, Bernhard T., Cheung, Eric F. C., Chong, Siow Ann, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J., Curtis, David, Davidson, Michael, Bigdeli, Tim B., Davis, Kenneth L., Degenhardt, Franziska, Favero, Jurgen Del, DeLisi, Lynn E., Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Cairns, Murray J., Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Farrell, Martilias S., Franke, Lude, Freedman, Robert, Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances (STRATA) Consortium and the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC), Ripke, S., Neale, B.M., Farh, K.H., Lee, P., Bulik-Sullivan, B., Collier, D.A., Huang, H., Pers, T.H., Agartz, I., Agerbo, E., Albus, M., Alexander, M., Amin, F., Bacanu, S.A., Begemann, M., Belliveau, R.A., Bene, J., Bergen, S.E., Bevilacqua, E., Black, D.W., Bruggeman, R., Buccola, N.G., Buckner, R.L., Byerley, W., Cahn, W., Cai, G., Campion, D., Cantor, R.M., Carr, V.J., Carrera, N., Catts, S.V., Chambert, K.D., Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W., Cheung, EFC, Chong, S.A., Cloninger, C.R., Cohen, D., Cohen, N., Cormican, P., Craddock, N., Crowley, J.J., Curtis, D., Davidson, M., Davis, K.L., Degenhardt, F., Favero, J.D., DeLisi, L.E., Demontis, D., Dikeos, D., Dinan, T., Djurovic, S., Donohoe, G., Drapeau, E., Duan, J., Dudbridge, F., Durmishi, N., Eichhammer, P., Eriksson, J., Escott-Price, V., Essioux, L., Farrell, M.S., Franke, L., Freedman, R., Freimer, N.B., Friedl, M., Friedman, J.I., Fromer, M., Genovese, G., Georgieva, L., Gershon, E.S., Giegling, I., Giusti-Rodríguez, P., Godard, S., Goldstein, J.I., Golimbet, V., Gopal, S., Gratten, J., Haan, L., Hammer, C., Hamshere, M.L., Hansen, M., Hansen, T., Haroutunian, V., Hartmann, A.M., Henskens, F.A., Herms, S., Hirschhorn, J.N., Hoffmann, P., Hofman, A., Hollegaard, M.V., Hougaard, D.M., Ikeda, M., Joa, I., Julià, A., Kahn, R.S., Kalaydjieva, L., Karachanak-Yankova, S., Karjalainen, J., Kavanagh, D., Keller, M.C., Kennedy, J.L., Khrunin, A., Kim, Y., Klovins, J., Knowles, J.A., Konte, B., Kucinskas, V., Kucinskiene, Z.A., Kuzelova-Ptackova, H., Kähler, A.K., Laurent, C., Keong, JLC, Lee, S.H., Lerer, B., Li, M., Li, T., Liang, K.Y., Lieberman, J., Limborska, S., Loughland, C.M., Lubinski, J., Lönnqvist, J., Macek, M., Magnusson, PKE, Maher, B.S., Maier, W., Mallet, J., Marsal, S., Mattheisen, M., Mattingsdal, M., McCarley, R.W., McDonald, C., McIntosh, A.M., Meier, S., Meijer, C.J., Melegh, B., Melle, I., Mesholam-Gately, R.I., Metspalu, A., Michie, P.T., Milani, L., Milanova, V., Mokrab, Y., Morris, D.W., Mors, O., Murphy, K.C., Myin-Germeys, I., Müller-Myhsok, B., Nelis, M., Nenadic, I., Nertney, D.A., Nestadt, G., Nicodemus, K.K., Nikitina-Zake, L., Nisenbaum, L., Nordin, A., O'Callaghan, E., O'Dushlaine, C., O'Neill, F.A., Oh, S.Y., Olincy, A., Olsen, L., Os, J.V., Pantelis, C., Papadimitriou, G.N., Papiol, S., Parkhomenko, E., Pato, M.T., Paunio, T., Pejovic-Milovancevic, M., Perkins, D.O., Pietiläinen, O., Pimm, J., Pocklington, A.J., Powell, J., Price, A., Pulver, A.E., Purcell, S.M., Quested, D., Rasmussen, H.B., Reichenberg, A., Reimers, M.A., Richards, A.L., Roffman, J.L., Roussos, P., Ruderfer, D.M., Salomaa, V., Sanders, A.R., Schall, U., Schubert, C.R., Schulze, T.G., Schwab, S.G., Scolnick, E.M., Scott, R.J., Seidman, L.J., Shi, J., Sigurdsson, E., Silagadze, T., Silverman, J.M., Sim, K., Slominsky, P., Smoller, J.W., So, H.C., Spencer, CCA, Stahl, E.A., Stefansson, H., Steinberg, S., Stogmann, E., Straub, R.E., Strengman, E., Strohmaier, J., Stroup, T.S., Subramaniam, M., Suvisaari, J., Svrakic, D.M., Szatkiewicz, J.P., Söderman, E., Thirumalai, S., Toncheva, D., Tosato, S., Veijola, J., Waddington, J., Walsh, D., Wang, D., Wang, Q., Webb, B.T., Weiser, M., Wildenauer, D.B., Williams, N.M., Williams, S., Witt, S.H., Wolen, A.R., Wong, EHM, Wormley, B.K., Xi, H.S., Zai, C.C., Zheng, X., Zimprich, F., Wray, N.R., Stefansson, K., Visscher, P.M., Adolfsson, R., Blackwood, DHR, Bramon, E., Buxbaum, J.D., Børglum, A.D., Cichon, S., Darvasi, A., Domenici, E., Ehrenreich, H., Esko, T., Gejman, P.V., Gill, M., Gurling, H., Hultman, C.M., Iwata, N., Jablensky, A.V., Jönsson, E.G., Kendler, K.S., Kirov, G., Knight, J., Lencz, T., Levinson, D.F., Li, Q.S., Liu, J., Malhotra, A.K., McCarroll, S.A., Moran, J.L., Mortensen, P.B., Nöthen, M.M., Ophoff, R.A., Palotie, A., Petryshen, T.L., Posthuma, D., Riley, B.P., Sham, P.C., Sklar, P., Clair, D.S., Weinberger, D.R., Wendland, J.R., Werge, T., Daly, M.J., Agbedjro, D., Stahl, D., Kapur, S., Millgate, E., Kepinska, A., Kravariti, E., Medical Research Council (UK), Cardiff University, Welsh Government, Health and Care Research Wales, European Commission, Academy of Medical Sciences (UK), Research Council of Norway, K. G. Jebsen Centres for Medical Research, National Institute for Health Research (UK), University College London, Government of Canada, University of Manitoba, Swedish Research Council, National Institute of Mental Health (US), Kings College London, Public Health Agency (Northern Ireland), The Psychiatry Research Trust, Maudsley Charity, Swiss National Science Foundation, Fondation Alamaya, Ministry of Health of the Czech Republic, Instituto de Salud Carlos III, Plan Nacional sobre Drogas (España), Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Wellcome Trust, and Universidad de Cantabria
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Male ,endocrine system ,Multifactorial Inheritance ,animal structures ,Psychiatry and Behavioral Health ,Online First ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Neurogenetics ,Medicinsk genetik ,Original Investigation ,Research ,Schizophrenia Sprectum and Other Psychotic Disorders ,Featured ,Genetics and genomics ,Psychiatry and Mental health ,Neurology ,Psychotic Disorders ,Schizophrenia ,Female ,Medical Genetics ,hormones, hormone substitutes, and hormone antagonists ,Comments ,Genome-Wide Association Study - Abstract
[Importance] About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts., [Objective] To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples., [Design, Setting, and Participants] Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G])., [Main Outcomes and Measures] GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition., [Results] The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04)., [Conclusions and Relevance] In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance., This work was supported by Medical Research Council Centre grant MR/L010305/1, Medical Research Council Program grant MR/P005748/1, and Medical Research Council Project grants MR/L011794/1 and MC_PC_17212 to Cardiff University and by the National Centre for Mental Health, funded by the Welsh Government through Health and Care Research Wales. This work acknowledges the support of the Supercomputing Wales project, which is partially funded by the European Regional Development Fund via the Welsh Government. Dr Pardiñas was supported by an Academy of Medical Sciences Springboard Award (SBF005\1083). Dr Andreassen was supported by the Research Council of Norway (grants 283798, 262656, 248980, 273291, 248828, 248778, and 223273); KG Jebsen Stiftelsen, South-East Norway Health Authority, and the European Union’s Horizon 2020 Research and Innovation Programme (grant 847776). Dr Ajnakina was supported by an National Institute for Health Research postdoctoral fellowship (PDF-2018-11-ST2-020). Dr Joyce was supported by the University College London Hospitals/UCL University College London Biomedical Research Centre. Dr Kowalec received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement (793530) from the government of Canada Banting postdoctoral fellowship programme and the University of Manitoba. Dr Sullivan was supported by the Swedish Research Council (Vetenskapsrådet, D0886501), the European Union’s Horizon 2020 programme (COSYN, 610307) and the US National Institute of Mental Health (U01 MH109528 and R01 MH077139). The Psychiatric Genomics Consortium was partly supported by the National Institute Of Mental Health (grants R01MH124873). The Sweden Schizophrenia Study was supported by the National Institute Of Mental Health (grant R01MH077139). The STRATA consortium was supported by a Stratified Medicine Programme grant to Dr MacCabe from the Medical Research Council (grant MR/L011794/1), which funded the research and supported Drs Pardiñas, Smart, Kassoumeri, Murray, Walters, and MacCabe. Dr Smart was supported by a Collaboration for Leadership in Applied Health Research and Care South London at King’s College Hospital National Health Service Foundation Trust. The AESOP (US) cohort was funded by the UK Medical Research Council (grant G0500817). The Belfast (UK) cohort was funded by the Research and Development Office of Northern Ireland. The Bologna (Italy) cohort was funded by the European Community’s Seventh Framework program (HEALTH-F2-2010–241909, project EU-GEI). The Genetics and Psychosis project (London, UK) cohort was funded by the UK National Institute of Health Research Specialist Biomedical Research Centre for Mental Health, South London and the Maudsley National Health Service Mental Health Foundation Trust (SLAM) and the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London; Psychiatry Research Trust; Maudsley Charity Research Fund; and the European Community’s Seventh Framework program (HEALTH-F2-2009-241909, project EU-GEI). The Lausanne (Switzerland) cohort was funded by the Swiss National Science Foundation (grants 320030_135736/1, 320030-120686, 324730-144064, 320030-173211, and 171804); the National Center of Competence in Research Synaptic Bases of Mental Diseases from the Swiss National Science Foundation (grant 51AU40_125759); and Fondation Alamaya. The Oslo (Norway) cohort was funded by the Research Council of Norway (grant 223273/F50, under the Centers of Excellence funding scheme, 300309, 283798) and the South-Eastern Norway Regional Health Authority (grants 2006233, 2006258, 2011085, 2014102, 2015088, and 2017-112). The Paris (France) cohort was funded by European Community’s Seventh Framework program (HEALTH-F2-2010–241909, project EU-GEI). The Prague (Czech Republic) cohort was funded by the Ministry of Health of the Czech Republic (grant NU20-04-00393). The Santander (Spain) cohort was funded by the following grants to Dr Crespo-Facorro: Instituto de Salud Carlos III (grants FIS00/3095, PI020499, PI050427, and PI060507), Plan Nacional de Drogas Research (grant 2005-Orden sco/3246/2004), SENY Fundatio Research (grant 2005-0308007), Fundacion Marques de Valdecilla (grant A/02/07, API07/011) and Ministry of Economy and Competitiveness and the European Fund for Regional Development (grants SAF2016-76046-R and SAF2013-46292-R). The West London (UK) cohort was funded by The Wellcome Trust (grants 042025, 052247, and 064607).
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- 2022
48. Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease
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Traschuetz, Andreas, Cortese, Andrea, Erer, Sevda, Schütz, Valerie Cornelia, Tarnutzer, Alexander A, Sturm, Marc, Haack, Tobias B, Vaucamps-Diedhiou, Nadège, Puccio, Helene, Schöls, Ludger, Klockgether, Thomas, van de Warrenburg, Bart P, Reich, Selina, Paucar, Martin, Timmann, Dagmar, Hilgers, Ralf-Dieter, Gazulla, Jose, Strupp, Michael, Moris, German, Filla, Alessandro, Houlden, Henry, Anheim, Mathieu, Infante, Jon, Dominik, Natalia, Basak, A Nazli, Synofzik, Matthis, Group, RFC1 Study, Barut, Banu Özen, Bilgic, Basar, Boz, Cavit, Cauquil, Cécile, Deininger, Natalie, Dufke, Claudia, Elibol, Bülent, Faber, Jennifer, Erbas, Furkan, Ertan, Sibel, Genc, Fatma, Giegling, Ina, Parman, Yesim, Rossi, Salvatore, Salcin, Celal, Tan, Meliha, Taştekin, Hilal, Tranchant, Christine, Jacobi, Heike, Uygun, Günes, Yassa, Özge Yagcioglu, Hartmann, Annette M, Rujescu, Dan, Montaut, Solveig, Echaniz-Laguna, Andoni, Universidad de Cantabria, Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Traschütz, A., Cortese, A., Reich, S., Dominik, N., Faber, J., Jacobi, H., Hartmann, A.M., Rujescu, D., Montaut, S., Echaniz-Laguna, A., Erer, S., Schütz, V. C., Tarnutzer, A. A., Sturm, M., Haack, T. B., Vaucamps-Diedhiou, N., Puccio, H., Schöls, L., Klockgether, T., van de Warrenburg, B. P., Paucar, M., Timmann, D., Hilgers, R. D., Gazulla, J., Strupp, M., Moris, G., Filla, A., Houlden, H., Anheim, M., Infante, J., Synofzik, M., RFC1 study group, Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Tübingen, Institute of Neurology - UCL/Queen Square [London, UK] (IN-UCL-QS), Università degli Studi di Pavia = University of Pavia (UNIPV), University Hospital Bonn, Heidelberg University Hospital [Heidelberg], Martin-Luther-Universität Halle Wittenberg (MLU), Hôpital de Hautepierre [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Petites Molécules de neuroprotection, neurorégénération et remyélinisation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Zürich [Zürich] = University of Zurich (UZH), Institute of Medical Genetics and Applied Genomics [Tübingen], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Radboud University Medical Center [Nijmegen], Karolinska Institute, University of Duisburg-Essen, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Hospital Universitario Miguel Servet, Ludwig-Maximilians University [Munich] (LMU), University of Naples Federico II = Università degli studi di Napoli Federico II, Martin-Luther-University Halle-Wittenberg, Universidad de Cantabria [Santander], Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), and univOAK, Archive ouverte
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0301 basic medicine ,Male ,Turkey ,Bilateral Vestibulopathy ,Medizin ,Disease ,Cohort Studies ,0302 clinical medicine ,Medicine ,Exome ,Replication Protein C ,RFC1 protein, human ,Dystonia ,DNA Repeat Expansion ,Genetics ,Middle Aged ,diagnostic imaging [Multiple System Atrophy] ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Magnetic Resonance Imaging ,Europe ,Phenotype ,diagnosis [Multiple System Atrophy] ,Vestibular Diseases ,Cohort ,Disease Progression ,Ataxia ,Disease progression ,Bilateral vestibulopathy ,Cohort studies ,DNA repeat expansion ,Female ,genetics [Multiple System Atrophy] ,medicine.symptom ,Adult ,medicine.medical_specialty ,Article ,03 medical and health sciences ,Atrophy ,Predictive Value of Tests ,Internal medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,ddc:610 ,Genetic Testing ,Aged ,Cerebellar ataxia ,business.industry ,Dysautonomia ,Chorea ,Multiple System Atrophy ,medicine.disease ,genetics [Replication Protein C] ,030104 developmental biology ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Objective: to delineate the full phenotypic spectrum, discriminative features, piloting longitudinal progression data, and sample size calculations of replication factor complex subunit 1 (RFC1) repeat expansions, recently identified as causing cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Methods: multimodal RFC1 repeat screening (PCR, Southern blot, whole-exome/genome sequencing-based approaches) combined with cross-sectional and longitudinal deep phenotyping in (1) cross-European cohort A (70 families) with ≥2 features of CANVAS or ataxia with chronic cough (ACC) and (2) Turkish cohort B (105 families) with unselected late-onset ataxia. Results: prevalence of RFC1 disease was 67% in cohort A, 14% in unselected cohort B, 68% in clinical CANVAS, and 100% in ACC. RFC1 disease was also identified in Western and Eastern Asian individuals and even by whole-exome sequencing. Visual compensation, sensory symptoms, and cough were strong positive discriminative predictors (>90%) against RFC1-negative patients. The phenotype across 70 RFC1-positive patients was mostly multisystemic (69%), including dysautonomia (62%) and bradykinesia (28%) (overlap with cerebellar-type multiple system atrophy [MSA-C]), postural instability (49%), slow vertical saccades (17%), and chorea or dystonia (11%). Ataxia progression was ≈1.3 Scale for the Assessment and Rating of Ataxia points per year (32 cross-sectional, 17 longitudinal assessments, follow-up ≤9 years [mean 3.1 years]) but also included early falls, variable nonlinear phases of MSA-C-like progression (SARA points 2.5-5.5 per year), and premature death. Treatment trials require 330 (1-year trial) and 132 (2-year trial) patients in total to detect 50% reduced progression. Conclusions: RFC1 disease is frequent and occurs across continents, with CANVAS and ACC as highly diagnostic phenotypes yet as variable, overlapping clusters along a continuous multisystemic disease spectrum, including MSA-C-overlap. Our natural history data help to inform future RFC1 treatment trials., European Union (EU); Horizon 2020; Research and Innovation Program; BMBF; E-Rare-3 network; PREPARE; DFG; EJP-RD network; PROSPAX; Solve-RD; University of Tubingen Medical Faculty; Clinician Scientist Program; Medical Research Council; Fondazione CARIPLO; ZonMW; Hersenstichting; Gossweiler Foundation; uniQure; Radboud University Medical Centre; Suna and İnan Kıraç Foundation; Koç University School of Medicine
- Published
- 2021
49. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders
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Laura M. Thornton, Paul Lichtenstein, Verneri Anttila, Diego Albani, Josep Antoni Ramos-Quiroga, Roger A.H. Adan, Monika Schlögelhofer, Stephen Sanders, Enrique Castelao, Klaus Berger, Nina Dalkner, Urs Heilbronner, Engilbert Sigurdsson, Pablo Mir, Fuquan Zhang, James T.R. Walters, Patrick F. Sullivan, Fragiskos Gonidakis, F. Kyle Satterstrom, Sara Marsal, Per Hoffmann, Amy Perry, Valentina Ciullo, Beate Herpertz-Dahlmann, Catharina Lavebratt, Kieran C. Murphy, Tammy Hedderly, Hyun Ju Hong, Evald Saemundsen, Sascha B. Fischer, Hailiang Huang, Andrew D. Grotzinger, Nienke Vulink, Murray B. Stein, Mark A. Frye, Laura J. Scott, David Curtis, Todd Lencz, Janiece E. DeSocio, Richard A. Belliveau, Eduard Vieta, Andrea Dietrich, Wade H. Berrettini, Kenneth S. Kendler, Marquis P. Vawter, Paul S. Nestadt, Michael E. Talkowski, Manuel Mattheisen, Ingrid Agartz, Elisa Docampo, Bernhard T. Baune, Stefan Ehrlich, Jolanta Lissowska, Felecia Cerrato, Terje Nærland, Robin M. Murray, Jennifer Reichert, Annette M. Hartmann, Hannelore Ehrenreich, Howard J. Edenberg, Katherine A. Halmi, Qingqin S. Li, Peristera Paschou, Marie Bækvad-Hansen, Esther Walton, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Frank Bellivier, Jungeun Song, D. Blake Woodside, Young Shin Kim, Jochen Seitz, Jacques Pantel, Palmiero Monteleone, Erika L. Nurmi, Rodney J. Scott, Kang Sim, Ekaterina A. Khramtsova, Udo Dannlowski, Rolf Adolfsson, Danielle Posthuma, Melissa J. Green, Laura Ibanez-Gomez, Jakob Grove, Elvira Bramon, Gregory L. Hanna, Cynthia M. Bulik, Yiran Guo, Stephan Ripke, Mary M. Robertson, Harald N. Aschauer, Adebayo Anjorin, Joanna Martin, Bertram Müller-Myhsok, Deborah Kaminská, Jose Guzman-Parra, Benedetta Nacmias, Erik G. Jönsson, Jonathan R. I. Coleman, Douglas F. Levinson, Hamdi Mbarek, Gun Peggy Knudsen, Karin Egberts, Mette Nyegaard, Patrik K. E. Magnusson, Mark Adams, Douglas Blackwood, Elisabeth B. Binder, Marcus Ising, Anna R. 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Leventhal, Giovanni Gambaro, Christos Androutsos, Jennifer Tübing, Marion Roberts, Annelie Nordin Adolfsson, Hakon Hakonarson, Dorothy E. Grice, Vaughan J. Carr, Konstantinos Tziouvas, Stephanie Zerwas, Cathy L. Barr, Michael Conlon O'Donovan, Per Qvist, Beate St Pourcain, Samuel Kuperman, Leila Karhunen, Jack Samuels, Markus M. Nöthen, Martien J H Kas, Alfonso Tortorella, Mikael Landén, Jennifer Crosbie, Marco A. Grados, Joanna M. Biernacka, Paul D. Arnold, Irene A. Malaty, Jurjen J. Luykx, Nicholas Bass, Naomi R. Wray, Catharina A. Hartman, Christina M. Hultman, Michael S. Okun, Brandon Wormley, Michael Bauer, Daniel J. Smith, Ian Jones, Kathryn Roeder, Brien P. Riley, Caroline M. Nievergelt, Katrin Gade, Sarah Kittel-Schneider, Roy H. Perlis, James R. Mitchell, Ziarih Hawi, James Lee, Liz Forty, William E. Bunney, Thomas Damm Als, Catherine Schaefer, Digby Quested, Matteo Cassina, Anna C. Koller, Patrick Turley, Agnes A. Steixner, Anu Raevuori, Assen Jablensky, Peter Holmans, Dong-Ho Song, S. Evelyn Stewart, Jan K. Buitelaar, Fernando S. Goes, Alexander Münchau, Ayman H. Fanous, Nicolas Ramoz, James B. Potash, Monica Gratacos Mayora, Tobias Banaschewski, Céline S. Reinbold, Renata Rizzo, Arianna Di Florio, Lenka Foretova, Gianfranco Spalletta, Aarno Palotie, Eleftheria Zeggini, Lawrence W. Brown, Julie K. O'Toole, Lynn E. DeLisi, Ulrich Schall, Mary Roberson, Barbara J. Coffey, Bryan J. Mowry, Murray J. Cairns, Dan J. Stein, Glyn Lewis, Marta Ribasés, C. Robert Cloninger, Bettina Konte, John B. Vincent, Duncan S. Palmer, Radhika Kandaswamy, Christine Ladd-Acosta, Lars Alfredsson, Frank Visscher, Ulrike Schmidt, Aiden Corvin, Susan L. Santangelo, Brenda W.J.H. Penninx, David J. Porteous, Tetsuya Ando, Arne E. Vaaler, Bru Cormand, Laura Carlberg, Claire Churchhouse, Manfred Stuhrmann, Niamh Mullins, Christine Søholm Hansen, Cathy L. Budman, Hartmut Imgart, Dan E. Arking, James J. 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B., Brandt, H., Burghardt, R., Carlberg, L., Cassina, M., Clementi, M., Courtet, P., Crawford, S., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., Degortes, D., Desocio, J. E., Dick, D. M., Dina, C., Docampo, E., Egberts, K., Ehrlich, S., Espeseth, T., Fernandez-Aranda, F., Fichter, M. M., Foretova, L., Forzan, M., Gambaro, G., Giegling, I., Gonidakis, F., Gorwood, P., Mayora, M. G., Guo, Y., Halmi, K. A., Hatzikotoulas, K., Hebebrand, J., Helder, S. G., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Imgart, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Julia, A., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kaye, W. H., Kennedy, M. A., Kim, Y. -R., Klareskog, L., Klump, K. L., Knudsen, G. P. S., Landen, M., Le Hellard, S., Levitan, R. D., Li, D., Lichtenstein, P., Maj, M., Marsal, S., Mcdevitt, S., Mitchell, J., Monteleone, P., Monteleone, A. M., Munn-Chernoff, M. A., Nacmias, B., Navratilova, M., O'Toole, J. 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A., Schaefer, C., Schulte, E. C., Shi, J., Smith, D. J., Thomson, P. A., Tiemeier, H., Uher, R., van der Auwera, S., Weissman, M. M., Alexander, M., Begemann, M., Bramon, E., Buccola, N. G., Cairns, M. J., Campion, D., Carr, V. J., Cloninger, C. R., Cohen, D., Collier, D. A., Corvin, A., Delisi, L. E., Donohoe, G., Dudbridge, F., Duan, J., Freedman, R., Gejman, P. V., Golimbet, V., Godard, S., Ehrenreich, H., Hartmann, A. M., Henskens, F. A., Ikeda, M., Iwata, N., Jablensky, A. V., Joa, I., Jonsson, E. G., Kelly, B. J., Knight, J., Konte, B., Laurent-Levinson, C., Lee, J., Lencz, T., Lerer, B., Loughland, C. M., Malhotra, A. K., Mallet, J., Mcdonald, C., Mitjans, M., Mowry, B. J., Murphy, K. C., Murray, R. M., O'Neill, F. A., Oh, S. -Y., Palotie, A., Pantelis, C., Pulver, A. E., Petryshen, T. L., Quested, D. J., Riley, B., Sanders, A. R., Schall, U., Schwab, S. G., Scott, R. J., Sham, P. C., Silverman, J. M., Sim, K., Steixner, A. A., Tooney, P. A., van Os, J., Vawter, M. P., Walsh, D., Weiser, M., Wildenauer, D. B., Williams, N. M., Wormley, B. K., Zhang, F., Androutsos, C., Arnold, P. D., Barr, C. L., Barta, C., Bey, K., Bienvenu, O. J., Black, D. W., Brown, L. W., Budman, C., Cath, D., Cheon, K. -A., Ciullo, V., Coffey, B. J., Cusi, D., Davis, L. K., Denys, D., Depienne, C., Dietrich, A., Eapen, V., Falkai, P., Fernandez, T. V., Garcia-Delgar, B., Geller, D. A., Gilbert, D. L., Grados, M. A., Greenberg, E., Grunblatt, E., Hagstrom, J., Hanna, G. L., Hartmann, A., Hedderly, T., Heiman, G. A., Heyman, I., Hong, H. J., Huang, A., Huyser, C., Ibanez-Gomez, L., Khramtsova, E. A., Kim, Y. K., Kim, Y. -S., King, R. A., Koh, Y. -J., Konstantinidis, A., Kook, S., Kuperman, S., Leventhal, B. L., Lochner, C., Ludolph, A. G., Madruga-Garrido, M., Malaty, I., Maras, A., Mccracken, J. T., Meijer, I. A., Mir, P., Morer, A., Muller-Vahl, K. R., Munchau, A., Murphy, T. L., Naarden, A., Nagy, P., Nestadt, G., Nestadt, P. S., Nicolini, H., Nurmi, E. L., Okun, M. S., Paschou, P., Piras, F., Pittenger, C., Plessen, K. J., Richter, M. A., Rizzo, R., Robertson, M., Roessner, V., Ruhrmann, S., Samuels, J. F., Sandor, P., Schlogelhofer, M., Shin, E. -Y., Singer, H., Song, D. -H., Song, J., Spalletta, G., Stein, D. J., Stewart, S. E., Storch, E. A., Stranger, B., Stuhrmann, M., Tarnok, Z., Tischfield, J. A., Tubing, J., Visscher, F., Vulink, N., Wagner, M., Walitza, S., Wanderer, S., Woods, M., Worbe, Y., Zai, G., Zinner, S. H., Sullivan, P. F., Franke, B., Daly, M. J., Bulik, C. M., Mcintosh, A. M., O'Donovan, M. C., Zheutlin, A., Andreassen, O. A., Borglum, A. D., Breen, G., Edenberg, H. J., Fanous, A. H., Faraone, S. V., Gelernter, J., Mathews, C. A., Mattheisen, M., Mitchell, K. S., Neale, M. C., Nurnberger, J. I., Ripke, S., Santangelo, S. L., Scharf, J. M., Stein, M. B., Thornton, L. M., Walters, J. T. R., Wray, N. R., Geschwind, D. H., Neale, B. M., Kendler, K. S., and Smoller, J. W.
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Netherlands Twin Register (NTR) ,cross-disorder genetics ,Medizin ,Genome-wide association study ,Tourette syndrome ,functional genomics ,gene expression ,genetic architecture ,genetic correlation ,GWAS ,neurodevelopment ,pleiotropy ,psychiatric disorders ,Psychiatric genetics ,0302 clinical medicine ,Pleiotropy ,functional genomic ,WIDE ASSOCIATION ,cross-disorder genetic ,0303 health sciences ,Mental Disorders ,Genetic Pleiotropy ,HUMAN BRAIN ,INSIGHTS ,Autism spectrum disorder ,Schizophrenia ,DISEASES ,GENETIC CORRELATIONS ,medicine.medical_specialty ,Neurogenesis ,Quantitative Trait Loci ,BF ,Biology ,GENOTYPE IMPUTATION ,Psychiatric geneticscross-disorder geneticspsychiatric disorderspleiotropyneurodevelopmentGWASgenetic correlationgene expressiongenetic architecturefunctional genomics ,Article ,General Biochemistry, Genetics and Molecular Biology ,psychiatric disorder ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,medicine ,Humans ,Genetic Predisposition to Disease ,Bipolar disorder ,TRANSCRIPTOME ,Psychiatry ,030304 developmental biology ,Gwas ,Psychiatric Genetics ,Cross-disorder Genetics ,Functional Genomics ,Gene Expression ,Genetic Architecture ,Genetic Correlation ,Neurodevelopment ,Psychiatric Disorders ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,IDENTIFICATION ,MUTATIONS ,medicine.disease ,Genetic architecture ,DEMETHYLASE ,RC0321 ,1182 Biochemistry, cell and molecular biology ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
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- 2019
50. Genome-wide association study supports the role of the immunological system and of the neurodevelopmental processes in response to haloperidol treatment
- Author
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Bettina Konte, Antonio Drago, Annette M. Hartmann, Marion Friedl, Ina Giegling, Dan Rujescu, Alessandro Serretti, Martin Schäfer, Drago, A., Giegling, I., Schafer, M., Hartmann, A.M., Konte, B., Friedl, M., Serretti, A., and Rujescu, D.
- Subjects
Adult ,Male ,Drug ,Genotype ,media_common.quotation_subject ,Genome-wide association study ,Bioinformatics ,Polymorphism, Single Nucleotide ,behavioral disciplines and activities ,Genetics ,Haloperidol ,Humans ,Medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Allele ,Molecular Biology ,Gene ,Alleles ,Genetics (clinical) ,media_common ,Genetic association ,Psychiatric Status Rating Scales ,business.industry ,Psychiatric Status Rating Scale ,Middle Aged ,medicine.disease ,Antipsychotic Agent ,Schizophrenia ,Immune System ,Molecular Medicine ,Female ,business ,Human ,Antipsychotic Agents ,Genome-Wide Association Study ,medicine.drug - Abstract
AIM: The aim of the study was to detect the genetic predictors of reseponse to haloperidol.BACKGROUND: Haloperidol is a benchmark drug for the pharmacological treatment of schizophrenia, but the genetics of its efficacy is yet to be elucidated.METHODS: A genome-wide association analysis was carried out in a small sample of patients treated with haloperidol (n=96) and the results were replicated in a larger sample of patients treated with second-generation antipsychotics or perphenazine (final n=169, available from the Clinical Antipsychotic Trials for Intervention Effectiveness study). The Positive and Negative Symptom Scale % score decrease was the outcome in both samples. The period of observation was restricted to 1 month in the replication sample and the most severe cases were included to best balance the replication. The quality control (QC) for the investigation and replication sample included a minor allele frequency at least 0.01, call rate at least 0.95, and Hardy-Weinberg equilibrium P at least 0.0001. The source for imputation was the 1000 Genomes Pilot+HapMap 3 dataset. In total 1 080 870 single nucleotide polymorphisms (SNPs) were available after imputation and QC in the investigation sample. After QC of real genotypes, locus-targeted imputations were restricted to windows of 10 kb on either side of the sentinel SNP in the replication sample. Sentinel SNPs were the most significant findings in the investigation sample. Analysis of variance was the test of choice, PLINK, SNPTEST, and GTOOL were used in the analysis.RESULTS: Two SNPs (rs7912580 and rs2412459) were associated with response in both samples, respectively, located in an intergenic region between the AT-rich interactive domain 5B (ARID5B, MRF1-like) gene and rhotekin 2 (RTKN2) gene, an intronic region located in the eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4) gene (P=1.358e-06 and 0.015 for the Positive and Negative Symptom Scale % total score decrease in the investigation and replication samples, respectively). The direction of association was opposite in the two samples, a finding that is sometimes reported as a flip-flop association.CONCLUSION: Heterozygosis for the ancestral allele was associated with the best improvement in the investigation sample and with poorer outcome in the replication sample. This discrepancy can be because of differences in the replication and investigation sample including the drugs used and the severity at baseline. Nevertheless, this finding is in line with two relevant hypothesis of schizophrenia, related to alterations in the immunological system (RTKN2) and in the neurodevelopment of the central nervous system (EIF2AK4). More studies are warranted to further investigate these associations.
- Published
- 2014
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