92 results on '"Palviainen T"'
Search Results
2. The association of depressive symptoms with perceived occupational noise exposure in young adults
- Author
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Heinonen-Guzejev, M, primary, Whipp, A M, additional, Wang, Z, additional, Anu Ranjit, A, additional, Palviainen, T, additional, van Kamp, I, additional, and Kaprio, J, additional
- Published
- 2023
- Full Text
- View/download PDF
3. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- Author
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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.
- Subjects
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
- Published
- 2021
4. Variants associated with HHIP expression have sex-differential effects on lung function [version 1; peer review: 2 approved]
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Fawcett, KA, Obeidat, M, Melbourne, C, Shrine, N, Guyatt, AL, John, C, Luan, J, Richmond, A, Moksnes, MR, Granell, R, Weiss, S, Imboden, M, May-Wilson, S, Hysi, P, Boutin, TS, Portas, L, Flexeder, C, Harris, SE, Wang, CA, Lyytikäinen, LP, Palviainen, T, Foong, RE, Keidel, D, Minelli, C, Langenberg, C, Bossé, Y, Van den Berge, M, Sin, DD, Hao, K, Campbell, A, Porteous, D, Padmanabhan, S, Smith, BH, Evans, DM, Ring, S, Langhammer, A, Hveem, K, Willer, C, Ewert, R, Stubbe, B, Pirastu, N, Klaric, L, Joshi, PK, Patasova, K, Massimo, M, Polasek, O, Starr, JM, Karrasch, S, Strauch, K, Meitinger, T, Rudan, I, Rantanen, T., Pietiläinen, K, Kähönen, M, Raitakari, OT, Hall, GL, Sly, PD, Pennell, CE, Kaprio, J, Lehtimäki, T, Vitart, V, Deary, IJ, Jarvis, D, Wilson, JF, Spector, T, Probst-Hensch, N, Wareham, NJ, Völzke, H, Henderson, J, Strachan, DP, Brumpton, BM, Hayward, C, Hall, IP, Tobin, MD, and Wain, LV
- Subjects
genome-wide interaction study ,HHIP ,lcsh:R ,lcsh:Medicine ,lung function ,genotyyppi ,sukupuoli ,hengityselimet ,toimintakyky ,expression ,sex ,lcsh:Q ,geeniekspressio ,geneettiset tekijät ,lcsh:Science ,keuhkot - Abstract
Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P
- Published
- 2020
5. Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes
- Author
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Wang, H., primary, Lane, J., additional, Jones, S., additional, Dashti, H., additional, Ollila, H., additional, Wood, A., additional, van Hees, V., additional, Brumpton, B., additional, Winsvold, B., additional, Kantojärvi, K., additional, Palviainen, T., additional, Cade, B., additional, Sofer, T., additional, Song, Y., additional, Patel, K., additional, Anderson, S., additional, Bechtold, D., additional, Bowden, J., additional, Emsley, R., additional, Kyle, S., additional, Little, M., additional, Loudon, A., additional, Scheer, F., additional, Purcell, S., additional, Richmond, R., additional, Spiegelhalder, K., additional, Tyrrell, J., additional, Zhu, X., additional, Hublin, C., additional, Kaprio, J., additional, Kristiansson, K., additional, Sulkava, S., additional, Paunio, T., additional, Hveem, K., additional, Nielsen, J., additional, Willer, C., additional, Zwart, J.-A., additional, Strand, L., additional, Frayling, T., additional, Ray, D., additional, Lawlor, D., additional, Rutter, M., additional, Weedon, M., additional, Redline, S., additional, and Saxena, R., additional
- Published
- 2019
- Full Text
- View/download PDF
6. Recent advancements in the development of radiation hard semiconductor detectors for S-LHC
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Fretwurst, E., Adey, J., Al-Ajili, A., Alfieri, G., Allport, P.P., Artuso, M., Assouak, S., Avset, B.S., Barabash, L., Barcz, A., Bates, R., Biagi, S.F., Bilei, G.M., Bisello, D., Blue, A., Blumenau, A., Boisvert, V., Bolla, G., Bondarenko, G., Borchi, E., Borrello, L., Bortoletto, D., Boscardin, M., Bosisio, L., Bowcock, T.J.V., Brodbeck, T.J., Broz, J., Bruzzi, M., Brzozowski, A., Buda, M., Buhmann, P., Buttar, C., Campabadal, F., Campbell, D., Candelori, A., Casse, G., Cavallini, A., Charron, S., Chilingarov, A., Chren, D., Cindro, V., Collins, P., Coluccia, R., Contarato, D., Coutinho, J., Creanza, D., Cunningham, L., Dalla Betta, G.-F., Dawson, I., de Boer, W., De Palma, M., Demina, R., Dervan, P., Dittongo, S., Dolezal, Z., Dolgolenko, A., Eberlein, T., Eremin, V., Fall, C., Fasolo, F., Ferbel, T., Fizzotti, F., Fleta, C., Focardi, E., Forton, E., Garcia, C., Garcia-Navarro, J.E., Gaubas, E., Genest, M.-H., Gill, K.A., Giolo, K., Glaser, M., Goessling, C., Golovine, V., González Sevilla, S., Gorelov, I., Goss, J., Gouldwell Bates, A., Grégoire, G., Gregori, P., Grigoriev, E., Grillo, A.A., Groza, A., Guskov, J., Haddad, L., Härkönen, J., Hauler, F., Hoeferkamp, M., Hönniger, F., Horazdovsky, T., Horisberger, R., Horn, M., Houdayer, A., Hourahine, B., Hughes, G., Ilyashenko, I., Irmscher, K., Ivanov, A., Jarasiunas, K., Johansen, K.M.H., Jones, B.K., Jones, R., Joram, C., Jungermann, L., Kalinina, E., Kaminski, P., Karpenko, A., Karpov, A., Kazlauskiene, V., Kazukauskas, V., Khivrich, V., Khomenkov, V., Kierstead, J., Klaiber-Lodewigs, J., Klingenberg, R., Kodys, P., Kohout, Z., Korjenevski, S., Koski, M., Kozlowski, R., Kozodaev, M., Kramberger, G., Krasel, O., Kuznetsov, A., Kwan, S., Lagomarsino, S., Lassila-Perini, K., Lastovetsky, V., Latino, G., Lazanu, I., Lazanu, S., Lebedev, A., Lebel, C., Leinonen, K., Leroy, C., Li, Z., Lindström, G., Linhart, V., Litovchenko, P., Litovchenko, A., Lo Giudice, A., Lozano, M., Luczynski, Z., Luukka, P., Macchiolo, A., Makarenko, L.F., Mandić, I., Manfredotti, C., Manna, N., Marti i Garcia, S., Marunko, S., Mathieson, K., Melone, J., Menichelli, D., Messineo, A., Metcalfe, J., Miglio, S., Mikuž, M., Miyamoto, J., Moll, M., Monakhov, E., Moscatelli, F., Naoumov, D., Nossarzewska-Orlowska, E., Nysten, J., Olivero, P., Oshea, V., Palviainen, T., Paolini, C., Parkes, C., Passeri, D., Pein, U., Pellegrini, G., Perera, L., Petasecca, M., Piemonte, C., Pignatel, G.U., Pinho, N., Pintilie, I., Pintilie, L., Polivtsev, L., Polozov, P., Popa, A., Popule, J., Pospisil, S., Pozza, A., Radicci, V., Rafí, J.M., Rando, R., Roeder, R., Rohe, T., Ronchin, S., Rott, C., Roy, A., Ruzin, A., Sadrozinski, H.F.W., Sakalauskas, S., Scaringella, M., Schiavulli, L., Schnetzer, S., Schumm, B., Sciortino, S., Scorzoni, A., Segneri, G., Seidel, S., Seiden, A., Sellberg, G., Sellin, P., Sentenac, D., Shipsey, I., Sicho, P., Sloan, T., Solar, M., Son, S., Sopko, B., Sopko, V., Spencer, N., Stahl, J., Stolze, D., Stone, R., Storasta, J., Strokan, N., Sudzius, M., Surma, B., Suvorov, A., Svensson, B.G., Tipton, P., Tomasek, M., Tsvetkov, A., Tuominen, E., Tuovinen, E., Tuuva, T., Tylchin, M., Uebersee, H., Uher, J., Ullán, M., Vaitkus, J.V., Velthuis, J., Verbitskaya, E., Vrba, V., Wagner, G., Wilhelm, I., Worm, S., Wright, V., Wunstorf, R., Yiuri, Y., Zabierowski, P., Zaluzhny, A., Zavrtanik, M., Zen, M., Zhukov, V., and Zorzi, N.
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- 2005
- Full Text
- View/download PDF
7. Development of radiation tolerant semiconductor detectors for the Super-LHC
- Author
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Moll, M., Adey, J., Al-Ajili, A., Alfieri, G., Allport, P.P., Artuso, M., Assouak, S., Avset, B.S., Barabash, L., Barcz, A., Bates, R., Biagi, S.F., Bilei, G.M., Bisello, D., Blue, A., Blumenau, A., Boisvert, V., Bolla, G., Bondarenko, G., Borchi, E., Borrello, L., Bortoletto, D., Boscardin, M., Bosisio, L., Bowcock, T.J.V., Brodbeck, T.J., Broz, J., Bruzzi, M., Brzozowski, A., Buda, M., Buhmann, P., Buttar, C., Campabadal, F., Campbell, D., Candelori, A., Casse, G., Cavallini, A., Charron, S., Chilingarov, A., Chren, D., Cindro, V., Collins, P., Coluccia, R., Contarato, D., Coutinho, J., Creanza, D., Cunningham, W., Dalla Betta, G. -F., Dawson, I., de Boer, W., De Palma, M., Demina, R., Dervan, P., Dittongo, S., Dolezal, Z., Dolgolenko, A., Eberlein, T., Eremin, V., Fall, C., Fasolo, F., Fizzotti, F., Fleta, C., Focardi, E., Forton, E., Fretwurst, E., Garcia, C., Garcia-Navarro, J.E., Gaubas, E., Genest, M. -H., Gill, K.A., Giolo, K., Glaser, M., Goessling, C., Golovine, V., González Sevilla, S., Gorelov, I., Goss, J., Gouldwell Bates, A., Grégoire, G., Gregori, P., Grigoriev, E., Grillo, A.A., Groza, A., Guskov, J., Haddad, L., Härkönen, J., Hauler, F., Hoeferkamp, M., Hönniger, F., Horazdovsky, T., Horisberger, R., Horn, M., Houdayer, A., Hourahine, B., Hughes, G., Ilyashenko, I., Irmscher, K., Ivanov, A., Jarasiunas, K., Johansen, K.M.H., Jones, B.K., Jones, R., Joram, C., Jungermann, L., Kalinina, E., Kaminski, P., Karpenko, A., Karpov, A., Kazlauskiene, V., Kazukauskas, V., Khivrich, V., Khomenkov, V., Kierstead, J., Klaiber-Lodewigs, J., Klingenberg, R., Kodys, P., Kohout, Z., Korjenevski, S., Koski, M., Kozlowski, R., Kozodaev, M., Kramberger, G., Krasel, O., Kuznetsov, A., Kwan, S., Lagomarsino, S., Lassila-Perini, K., Lastovetsky, V., Latino, G., Lazanu, S., Lazanu, I., Lebedev, A., Lebel, C., Leinonen, K., Leroy, C., Li, Z., Lindström, G., Linhart, V., Litovchenko, A., Litovchenko, P., Lo Giudice, A., Lozano, M., Luczynski, Z., Luukka, P., Macchiolo, A., Makarenko, L.F., Mandić, I., Manfredotti, C., Manna, N., Marti i Garcia, S., Marunko, S., Mathieson, K., Melone, J., Menichelli, D., Messineo, A., Metcalfe, J., Miglio, S., Mikuž, M., Miyamoto, J., Monakhov, E., Moscatelli, F., Naoumov, D., Nossarzewska-Orlowska, E., Nysten, J., Olivero, P., OShea, V., Palviainen, T., Paolini, C., Parkes, C., Passeri, D., Pein, U., Pellegrini, G., Perera, L., Petasecca, M., Piemonte, C., Pignatel, G.U., Pinho, N., Pintilie, I., Pintilie, L., Polivtsev, L., Polozov, P., Popa, A., Popule, J., Pospisil, S., Pozza, A., Radicci, V., Rafí, J.M., Rando, R., Roeder, R., Rohe, T., Ronchin, S., Rott, C., Roy, A., Ruzin, A., Sadrozinski, H.F.W., Sakalauskas, S., Scaringella, M., Schiavulli, L., Schnetzer, S., Schumm, B., Sciortino, S., Scorzoni, A., Segneri, G., Seidel, S., Seiden, A., Sellberg, G., Sellin, P., Sentenac, D., Shipsey, I., Sicho, P., Sloan, T., Solar, M., Son, S., Sopko, B., Sopko, V., Spencer, N., Stahl, J., Stolze, D., Stone, R., Storasta, J., Strokan, N., Sudzius, M., Surma, B., Suvorov, A., Svensson, B.G., Tipton, P., Tomasek, M., Tsvetkov, A., Tuominen, E., Tuovinen, E., Tuuva, T., Tylchin, M., Uebersee, H., Uher, J., Ullán, M., Vaitkus, J.V., Velthuis, J., Verbitskaya, E., Vrba, V., Wagner, G., Wilhelm, I., Worm, S., Wright, V., Wunstorf, R., Yiuri, Y., Zabierowski, P., Zaluzhny, A., Zavrtanik, M., Zen, M., Zhukov, V., and Zorzi, N.
- Published
- 2005
- Full Text
- View/download PDF
8. Radiation-hard semiconductor detectors for SuperLHC
- Author
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Bruzzi, M., Adey, J., Al-Ajili, A., Alexandrov, P., Alfieri, G., Allport, P.P., Andreazza, A., Artuso, M., Assouak, S., Avset, B.S., Barabash, L., Baranova, E., Barcz, A., Basile, A., Bates, R., Belova, N., Biagi, S.F., Bilei, G.M., Bisello, D., Blue, A., Blumenau, A., Boisvert, V., Bolla, G., Bondarenko, G., Borchi, E., Borrello, L., Bortoletto, D., Boscardin, M., Bosisio, L., V. Bowcock, T.J., Brodbeck, T.J., Broz, J., Brukhanov, A., Brzozowski, A., Buda, M., Buhmann, P., Buttar, C., Campabadal, F., Campbell, D., Candelori, A., Casse, G., Cavallini, A., Chilingarov, A., Chren, D., Cindro, V., Citterio, M., Collins, P., Coluccia, R., Contarato, D., Coutinho, J., Creanza, D., Cunningham, W., Cvetkov, V., Dalla Betta, G.-F., Davies, G., Dawson, I., de Boer, W., De Palma, M., Demina, R., Dervan, P., Dierlamm, A., Dittongo, S., Dobrzanski, L., Dolezal, Z., Dolgolenko, A., Eberlein, T., Eremin, V., Fall, C., Fasolo, F., Ferbel, T., Fizzotti, F., Fleta, C., Focardi, E., Forton, E., Franchenko, S., Fretwurst, E., Gamaz, F., Garcia, C., Garcia-Navarro, J.E., Gaubas, E., Genest, M.-H., Gill, K.A., Giolo, K., Glaser, M., Goessling, C., Golovine, V., González Sevilla, S., Gorelov, I., Goss, J., Gouldwell, A., Grégoire, G., Gregori, P., Grigoriev, E., Grigson, C., Grillo, A., Groza, A., Guskov, J., Haddad, L., Härkönen, J., Harding, R., Hauler, F., Hayama, S., Hoeferkamp, M., Hönniger, F., Horazdovsky, T., Horisberger, R., Horn, M., Houdayer, A., Hourahine, B., Hruban, A., Hughes, G., Ilyashenko, I., Irmscher, K., Ivanov, A., Jarasiunas, K., Jin, T., Jones, B.K., Jones, R., Joram, C., Jungermann, L., Kalinina, E., Kaminski, P., Karpenko, A., Karpov, A., Kazlauskiene, V., Kazukauskas, V., Khivrich, V., Khomenkov, V., Kierstead, J., Klaiber-Lodewigs, J., Kleverman, M., Klingenberg, R., Kodys, P., Kohout, Z., Korjenevski, S., Kowalik, A., Kozlowski, R., Kozodaev, M., Kramberger, G., Krasel, O., Kuznetsov, A., Kwan, S., Lagomarsino, S., Lari, T., Lassila-Perini, K., Lastovetsky, V., Latino, G., Latushkin, S., Lazanu, S., Lazanu, I., Lebel, C., Leinonen, K., Leroy, C., Li, Z., Lindström, G., Lindstrom, L., Linhart, V., Litovchenko, A., Litovchenko, P., Litvinov, V., Lo Giudice, A., Lozano, M., Luczynski, Z., Luukka, P., Macchiolo, A., Mainwood, A., Makarenko, L.F., Mandić, I., Manfredotti, C., Marti i Garcia, S., Marunko, S., Mathieson, K., Mozzanti, A., Melone, J., Menichelli, D., Meroni, C., Messineo, A., Miglio, S., Mikuž, M., Miyamoto, J., Moll, M., Monakhov, E., Moscatelli, F., Murin, L., Nava, F., Naoumov, D., Nossarzewska-Orlowska, E., Nummela, S., Nysten, J., Olivero, P., Oshea, V., Palviainen, T., Paolini, C., Parkes, C., Passeri, D., Pein, U., Pellegrini, G., Perera, L., Petasecca, M., Piatkowski, B., Piemonte, C., Pignatel, G.U., Pinho, N., Pintilie, I., Pintilie, L., Polivtsev, L., Polozov, P., Popa, A.I., Popule, J., Pospisil, S., Pucker, G., Radicci, V., Rafí, J.M., Ragusa, F., Rahman, M., Rando, R., Roeder, R., Rohe, T., Ronchin, S., Rott, C., Roy, P., Roy, A., Ruzin, A., Ryazanov, A., Sadrozinski, H.F.W., Sakalauskas, S., Scaringella, M., Schiavulli, L., Schnetzer, S., Schumm, B., Sciortino, S., Scorzoni, A., Segneri, G., Seidel, S., Seiden, A., Sellberg, G., Sellin, P., Sentenac, D., Shipsey, I., Sicho, P., Sloan, T., Solar, M., Son, S., Sopko, B., Spencer, N., Stahl, J., Stavitski, I., Stolze, D., Stone, R., Storasta, J., Strokan, N., Strupinski, W., Sudzius, M., Surma, B., Suuronen, J., Suvorov, A., Svensson, B.G., Tipton, P., Tomasek, M., Troncon, C., Tsvetkov, A., Tuominen, E., Tuovinen, E., Tuuva, T., Tylchin, M., Uebersee, H., Uher, J., Ullán, M., Vaitkus, J.V., Vanni, P., Velthuis, J., Verzellesi, G., Verbitskaya, E., Vrba, V., Wagner, G., Wilhelm, I., Worm, S., Wright, V., Wunstorf, R., Zabierowski, P., Zaluzhny, A., Zavrtanik, M., Zen, M., Zhukov, V., and Zorzi, N.
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9. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (vol 9, 2098, 2018)
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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
10. 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., KARLSSON, R., KNOWLES, E., Lahti, J., Leber, M., MATHER, K. A., Melle, I., Morris, D., OLDMEADOW, C., PALVIAINEN, T., PAYTON, A., PAZOKI, R., PETROVIC, K., Reynolds, C. A., SARGURUPREMRAJ, M., Scholz, M., Smith, J. A., SMITH, A. V., TERZIKHAN, N., THALAMUTHU, A., TROMPET, S., VAN DER LEE, S. J., WARE, E. B., WINDHAM, B. G., WRIGHT, M. J., Yang, J., Yu, J., Ames, D., Amin, N., Amouyel, P., ANDREASSEN, O. A., ARMSTRONG, N. J., ASSAREH, A. A., ATTIA, J. R., ATTIX, D., AVRAMOPOULOS, D., BENNETT, D. A., BOHMER, A. C., BOYLE, P. A., BRODATY, H., Campbell, H., CANNON, T. D., CIRULLI, E. T., CONGDON, E., CONLEY, E. D., CORLEY, J., COX, S. R., DALE, A. M., DEHGHAN, A., Dick, D., Dickinson, D., ERIKSSON, J. G., EVANGELOU, E., FAUL, J. D., Ford, I., FREIMER, N. A., Gao, H., Giegling, I., GILLESPIE, N. A., GORDON, S. D., GOTTESMAN, R. F., GRISWOLD, M. E., GUDNASON, V., HARRIS, T. B., HARTMANN, A. M., Hatzimanolis, A., Heiss, G., HOLLIDAY, E. G., Joshi, P. K., KAHONEN, M., KARDIA, S. L. R., KARLSSON, I., KLEINEIDAM, L., KNOPMAN, D. S., KOCHAN, N. A., Konte, B., KWOK, J. B., LE HELLARD, S., Lee, T., LEHTIMAKI, T., Li, S. C., Lill, C. M., Liu, T., KOINI, M., London, E., LONGSTRETH, W. T., Jr., LOPEZ, O. L., LOUKOLA, A., LUCK, T., LUNDERVOLD, A. J., LUNDQUIST, A., LYYTIKAINEN, L. P., Martin, N. G., MONTGOMERY, G. W., MURRAY, A. D., NEED, A. C., NOORDAM, R., Nyberg, L., OLLIER, W., PAPENBERG, G., PATTIE, A., POLASEK, O., POLDRACK, R. A., PSATY, B. M., REPPERMUND, S., RIEDEL-HELLER, S. G., ROSE, R. J., ROTTER, J. I., ROUSSOS, P., ROVIO, S. P., SABA, Y., SABB, F. W., SACHDEV, P. S., SATIZABAL, C. L., Schmid, M., Scott, R. J., SCULT, M. A., SIMINO, J., SLAGBOOM, P. E., SMYRNIS, N., Soumare, A., Stefanis, N. C., STOTT, D. J., STRAUB, R. E., SUNDET, K., Taylor, A. M., TAYLOR, K. D., TZOULAKI, I., Tzourio, C., Uitterlinden, A., Vitart, V., VOINESKOS, A. N., Kaprio, J., Wagner, M., Wagner, H., WEINHOLD, L., WEN, K. H., WIDEN, E., Yang, Q., Zhao, W., ADAMS, H. H. H., ARKING, D. E., Bilder, R. M., BITSIOS, P., BOERWINKLE, E., CHIBA-FALEK, O., Corvin, A., DE JAGER, P. L., Debette, S., Donohoe, G., Elliott, P., FITZPATRICK, A. L., Gill, M., GLAHN, D. C., HAGG, S., HANSELL, N. K., HARIRI, A. R., Ikram, M. A., JUKEMA, J. W., VUOKSIMAA, E., KELLER, M. C., KREMEN, W. S., LAUNER, L., LINDENBERGER, U., Palotie, A., PEDERSEN, N. L., PENDLETON, N., PORTEOUS, D. J., RAIKKONEN, K., RAITAKARI, O. T., Ramirez, A., REINVANG, I., RUDAN, I., DAN, Rujescu, Schmidt, R., Schmidt, H., SCHOFIELD, P. W., STARR, J. M., STEEN, V. M., TROLLOR, J. N., TURNER, S. T., VAN DUIJN, C. M., VILLRINGER, A., WEINBERGER, D. R., WEIR, D. R., WILSON, J. F., Malhotra, A., MCINTOSH, A. M., GALE, C. R., SESHADRI, S., MOSLEY, T. H., Jr., BRESSLER, J., Lencz, T., DEARY, I. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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VINTAGE ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,HEALTHY ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) - Abstract
Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.
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- 2019
11. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use
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Liu, M, Jiang, Y, Wedow, R, Li, Y, Brazel, DM, Chen, F, Datta, G, Davila-Velderrain, J, McGuire, D, Tian, C, Zhan, X, Team, 23Andme Research, Psychiatry, Hunt All-In, Choquet, H, Docherty, AR, Faul, JD, Foerster, JR, Fritsche, LG, Gabrielsen, ME, Gordon, SD, Haessler, J, Hottenga, J-J, Huang, H, Jang, S-K, Jansen, PR, Ling, Y, Mägi, R, Matoba, N, McMahon, G, Mulas, A, Orrù, V, Palviainen, T, Pandit, A, Reginsson, GW, Skogholt, AH, Smith, JA, Taylor, AE, Turman, C, Willemsen, G, Young, H, Young, KA, Zajac, GJM, Zhao, W, Zhou, W, Bjornsdottir, G, Boardman, JD, Boehnke, M, Boomsma, DI, Chen, C, Cucca, F, Davies, GE, Eaton, CB, Ehringer, MA, Esko, T, Fiorillo, E, Gillespie, NA, Gudbjartsson, DF, Haller, T, Harris, KM, Heath, AC, Hewitt, JK, Hickie, IB, Hokanson, JE, Hopfer, CJ, Hunter, DJ, Iacono, WG, Johnson, EO, Kamatani, Y, Kardia, SLR, Keller, MC, Kellis, M, Kooperberg, C, Kraft, P, Krauter, KS, Laakso, M, Lind, PA, Loukola, A, Lutz, SM, Madden, PAF, Martin, NG, McGue, M, McQueen, MB, Medland, SE, Metspalu, A, Mohlke, KL, Nielsen, JB, Okada, Y, Peters, U, Polderman, TJC, Posthuma, D, Reiner, AP, Rice, JP, Rimm, E, Rose, RJ, Runarsdottir, V, Stallings, MC, Stančáková, A, Stefansson, H, Thai, KK, Tindle, HA, Tyrfingsson, T, Wall, TL, Weir, DR, Weisner, C, Whitfield, JB, Winsvold, BS, Yin, J, Zuccolo, L, Bierut, LJ, Hveem, K, Lee, JJ, Munafò, MR, Saccone, NL, Willer, CJ, Cornelis, MC, David, SP, Hinds, DA, Jorgenson, E, Kaprio, J, Stitzel, JA, Stefansson, K, Thorgeirsson, TE, Abecasis, G, Liu, DJ, Vrieze, S, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, APH - Methodology, Human genetics, Amsterdam Reproduction & Development (AR&D), APH - Aging & Later Life, and Human Genetics
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Male ,Netherlands Twin Register (NTR) ,Smoking/genetics ,ved/biology.organism_classification_rank.species ,Alcohol ,Genome-wide association study ,Brain and Behaviour ,chemistry.chemical_compound ,0302 clinical medicine ,Tobacco Use Disorder/genetics ,Tobacco/adverse effects ,Genetics ,0303 health sciences ,Smoking ,Tobacco and Alcohol ,public health ,Tobacco Use Disorder ,Middle Aged ,3. Good health ,Phenotype ,psychiatric disorders ,Genetic Variation/genetics ,Meta-analysis ,Genome-Wide Association Study/methods ,Female ,Physical and Mental Health ,Risk ,Alcohol Drinking ,psychology ,Biology ,Article ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Tobacco ,Humans ,Model organism ,Gene ,030304 developmental biology ,Genetic association ,ved/biology ,Genetic Variation ,Alcohol Drinking/genetics ,Heritability ,chemistry ,genome-wide association studies ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6,7,8,9,10,11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures. © 2019. This is the authors’ accepted and refereed manuscript to the article.
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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).
- Published
- 2019
13. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
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Davies, G, Lam, M, Harris, SE, Trampush, JW, Luciano, M, Hill, WD, Hagenaars, SP, Ritchie, SJ, Marioni, RE, Fawns-Ritchie, C, Liewald, DCM, Okely, JA, Ahola-Olli, AV, Barnes, CLK, Bertram, L, Bis, JC, Burdick, KE, Christoforou, A, Derosse, P, Djurovic, S, Espeseth, T, Giakoumaki, S, Giddaluru, S, Gustavson, DE, Hayward, C, Hofer, E, Ikram, MA, Karlsson, R, Knowles, E, Lahti, J, Leber, M, Li, S, Mather, KA, Melle, I, Morris, D, Oldmeadow, C, Palviainen, T, Payton, A, Pazoki, R, Petrovic, K, Reynolds, CA, Sargurupremraj, M, Scholz, M, Smith, JA, Smith, AV, Terzikhan, N, Thalamuthu, A, Trompet, S, Van Der Lee, SJ, Ware, EB, Windham, BG, Wright, MJ, Yang, J, Yu, J, Ames, D, Amin, N, Amouyel, P, Andreassen, OA, Armstrong, NJ, Assareh, AA, Attia, JR, Attix, D, Avramopoulos, D, Bennett, DA, Böhmer, AC, Boyle, PA, and Brodaty, H
- Abstract
© 2018 The Author(s). General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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- 2018
14. Author Correction: Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis
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Waage, J, Standl, M, Curtin, JA, Jessen, LE, Thorsen, J, Tian, C, Schoettler, N, 23andMe Research Team, AAGC collaborators, Flores, C, Abdellaoui, A, Ahluwalia, TS, Alves, AC, Amaral, AFS, Antó, JM, Arnold, A, Barreto-Luis, A, Baurecht, H, van Beijsterveldt, CEM, Bleecker, ER, Bonàs-Guarch, S, Boomsma, DI, Brix, S, Bunyavanich, S, Burchard, EG, Chen, Z, Curjuric, I, Custovic, A, den Dekker, HT, Dharmage, SC, Dmitrieva, J, Duijts, L, Ege, MJ, Gauderman, WJ, Georges, M, Gieger, C, Gilliland, F, Granell, R, Gui, H, Hansen, T, Heinrich, J, Henderson, J, Hernandez-Pacheco, N, Holt, P, Imboden, M, Jaddoe, VWV, Jarvelin, M-R, Jarvis, DL, Jensen, KK, Jónsdóttir, I, Kabesch, M, Kaprio, J, Kumar, A, Lee, Y-A, Levin, AM, Li, X, Lorenzo-Diaz, F, Melén, E, Mercader, JM, Meyers, DA, Myers, R, Nicolae, DL, Nohr, EA, Palviainen, T, Paternoster, L, Pennell, CE, Pershagen, G, Pino-Yanes, M, Probst-Hensch, NM, Rüschendorf, F, Simpson, A, Stefansson, K, Sunyer, J, Sveinbjornsson, G, Thiering, E, Thompson, PJ, Torrent, M, Torrents, D, Tung, JY, Wang, CA, Weidinger, S, Weiss, S, Willemsen, G, Williams, LK, Ober, C, Hinds, DA, Ferreira, MA, Bisgaard, H, Strachan, DP, and Bønnelykke, K
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ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION ,ComputingMethodologies_COMPUTERGRAPHICS - Abstract
In the version of this article initially published, in Fig. 3, the y-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.
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- 2018
15. Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis
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Waage, J, Standl, M, Curtin, JA, Jessen, L, Thorsen, J, Tian, C, Schoettler, N, The 23andMe Research Team, AAGC Collaborators, Flores, C, Abdellaoui, A, Ahluwalia, TS, Alves, A, Amaral, AFS, Antó, JM, Arnold, A, Barreto-Luis, A, Baurecht, H, van Beijsterveldt, CEM, Bleecker, ER, Bonàs-Guarch, S, Boomsma, D, Brix, S, Bunyavanich, S, Burchard, E, Chen, Z, Curjuric, I, Custovic, A, den Dekker, HT, Dharmage, SC, Dmitrieva, J, Duijts, L, Ege, MJ, Gauderman, WJ, Georges, M, Gieger, C, Gilliland, F, Granell, R, Gui, H, Hansen, T, Heinrich, J, Henderson, J, Hernandez-Pacheco, N, Holt, P, Imboden, M, Jaddoe, VWV, Jarvelin, M-R, Jarvis, DL, Jensen, KK, Jónsdóttir, I, Kabesch, M, Kaprio, J, Kumar, A, Lee, Y-A, Levin, AM, Li, X, Lorenzo-Diaz, F, Melén, E, Mercader, JM, Meyers, DA, Myers, R, Nicolae, DL, Nohr, EA, Palviainen, T, Paternoster, L, Pennell, C, Pershagen, G, Pino-Yanes, M, Probst-Hensch, NM, Rüschendorf, F, Simpson, A, Stefansson, K, Sunyer, J, Sveinbjornsson, G, Thiering, E, Thompson, PJ, Torrent, M, Torrents, D, Tung, JY, Wang, CA, Weidinger, S, Weiss, S, Willemsen, G, Williams, LK, Ober, C, Hinds, DA, Ferreira, MA, Bisgaard, H, Strachan, DP, and Bønnelykke, K
- Abstract
Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.
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- 2018
16. SNPs associated withHHIPexpression have differential effects on lung function in males and females
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Fawcett, KA, primary, Obeidat, M, additional, Melbourne, CA, additional, Shrine, N, additional, Guyatt, AL, additional, John, C, additional, Luan, J, additional, Richmond, A, additional, Moksnes, MR, additional, Granell, R, additional, Weiss, S, additional, Imboden, M, additional, May-Wilson, S, additional, Hysi, P, additional, Boutin, TS, additional, Portas, L, additional, Flexeder, C, additional, Harris, SE, additional, Wang, CA, additional, Lyytikäinen, L, additional, Palviainen, T, additional, Foong, RE, additional, Keidel, D, additional, Minelli, C, additional, Langenberg, C, additional, Bossé, Y, additional, van den, Berge M, additional, Sin, D, additional, Hao, K, additional, Campbell, A, additional, Porteous, D, additional, Padmanabhan, S, additional, Smith, BH, additional, Evans, D, additional, Ring, S, additional, Langhammer, A, additional, Hveem, K, additional, Willer, C, additional, Ewert, R, additional, Stubbe, B, additional, Pirastu, N, additional, Klaric, L, additional, Joshi, PK, additional, Patasova, K, additional, Massimo, M, additional, Polasek, O, additional, Starr, JM, additional, Rudan, I, additional, Rantanen, T, additional, Pietiläinen, K, additional, Kähönen, M, additional, Raitakari, OT, additional, Hall, GL, additional, Sly, PD, additional, Pennell, CE, additional, Kaprio, J, additional, Lehtimäki, T, additional, Vitart, V, additional, Deary, IJ, additional, Jarvis, D, additional, Wilson, JF, additional, Spector, T, additional, Probst-Hensch, N, additional, Wareham, N, additional, Völzke, H, additional, Henderson, J, additional, Strachan, D, additional, Brumpton, BM, additional, Hayward, C, additional, Hall, IP, additional, Tobin, MD, additional, and Wain, LV, additional
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- 2019
- Full Text
- View/download PDF
17. A genome-wide association study of allergic rhinitis in 216 361 individuals identifies several novel susceptibility loci and increases knowledge on genetic pathways and cell types involved in disease etiology
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Waage, JE, Standl, M, Paternoster, L, Tian, C, James, A, Granell, R, Bunyavanich, S, Myers, R, Kreiner-Moller, E, Palviainen, T, Den Dekker, M, Ruschendorf, F, Barreto-Luis, A, Ahluwalia, T, Vilor-Tejedor, N, Curtin, J, Alves, A, Abdellaoui, A, Wang, C, Levin, A, Kaprio, J, Lee, Y-A, Brueske, I, Flores, C, Nohr, E, Sunyer, J, Boomsma, D, Pennel, C, Williams, K, Weiss, S, Simpson, A, Custovic, A, Ferreira, M, Duijts, L, Jarvelin, M-R, Ober, C, Henderson, J, Hinds, D, Strachan, D, Bisgaard, H, Bonnelykke, K, and Medical Research Council (MRC)
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Science & Technology ,Allergy ,1107 Immunology ,Immunology ,Life Sciences & Biomedicine - Published
- 2015
18. Investigation of voltages and electric fields in silicon semi 3D radiation detectors using Silvaco/ATLAS simulation tool and a scanning electron microscope.
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Palviainen, T., Leinonen, K., Tuuva, T., Eranen, S., Harkonen, J., Luukka, P., and Tuovinen, E.
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- 2005
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19. RD50 status report 2005: Radiation hard semiconductor devices for very high luminosity colliders
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Campabadal, F., Fleta, C., Lozano, M., Pellegrini, G., Rafi, J. M., Ullan, M., Ambrico, M., Creanza, D., Palma, M., Ligonzo, T., Manna, N., Radicci, V., Schiavulli, L., Irmscher, K., Wagner, G., Kierstead, J., Li, Zheng, Cavallini, A., Buda, M., Lazanu, S., Pintilie, L., Pintilie, I., Popa, A. I., Lazanu, I., Collins, P., Gill, K. A., Glaser, M., Joram, C., Hoedlmoser, H., Moll, M., Gossling, C., Klaiber-Lodewigs, J., Klingenberg, R., Krasel, O., Weber, J., Wunstorf, R., Roder, R., Stolze, D., Uebersee, H., Adey, J., Blumenau, A., Coutinho, J., Eberlein, T., Fall, C., Goss, J., Hourahine, B., Jones, R., Pinho, N., Coluccia, R., Kwan, S., Sellberg, G., Borchi, E., Bruzzi, M., Focardi, E., Lagomarsino, S., Macchiolo, A., Menichelli, D., Miglio, S., Scaringella, M., Sciortino, Silvio, Tosi, C., Eckert, S., Ehrich, T., Kuhn, S., Parzefall, U., Bates, R., Blue, A., Bussey, P., Buttar, C., Cunningham, W., Bates, A. G., Haddad, L., James, G., Mathieson, K., Melone, J., O Shea, V., Parkes, C., Pennicard, D., Saavedra, A., Buhmann, P., Contarato, D., Fretwurst, E., Honniger, F., Lindstrom, G., Pein, U., Stahl, J., Harkonen, J., Lassila-Perini, K., Luukka, P., Nysten, J., Tuominen, E., Tuovinen, E., Eremin, V., Ilyashenko, I., Ivanov, A., Kalinina, E., Lebedev, A., Strokan, N., Verbitskaya, E., Barcz, A., Brzozowski, A., Kaminski, P., Kozlowski, R., Kozubal, M., Luczynski, Z., Nossarzewska-Orlowska, E., Surma, B., Zabierowski, P., Boer, W., Furgeri, A., Hartmann, F., Hauler, F., Zhukov, V., Barabash, L., Dolgolenko, A., Groza, A., Karpenko, A., Khivrich, V., Lastovetsky, V., Litovchenko, P., Polivtsev, L., Brodbeck, T. J., Campbell, D., Chilingarov, A., Hughes, G., Jones, B. K., Sloan, T., Koski, M., Leinonen, K., Palviainen, T., Tuuva, T., Allport, P. P., Biagi, S. F., Bowcock, T. J. V., Casse, G., Velthuis, J., Vladimir Cindro, Dolenc, I., Kramberger, G., Mandic, I., Mikuz, M., Zavrtanik, M., Assouak, S., Forton, E., Gregoire, G., Lemaitre, V., Kazuchits, N., Makarenko, L., Charron, S., Genest, M. H., Houdayer, A., Lebel, C., Leroy, C., Bondarenko, G., Golovin, V., Grigoriev, E., Karpov, A., Kazakov, S., Rogozhkin, S., Zaluzhny, A., Gorelov, I., Hoeferkamp, M., Latino, G., Naumov, D., Seidel, S., Alfieri, G., Johansen, K. M. H., Kuznetsov, A., Monakhov, E., Svensson, B. G., Bisello, D., Candelori, A., Khomenkov, V., Litovchenko, A., Pantano, D., Rando, R., Bilei, G. M., Moscatelli, F., Passeri, D., Petasecca, M., Pignatel, G. U., Scorzoni, A., Borrello, L., Messineo, A., Segneri, G., Sentenac, D., Popule, J., Sicho, P., Tomasek, M., Vrba, V., Chren, D., Horazdovsky, T., Kohout, Z., Linhart, V., Pospisil, S., Solar, M., Sopko, V., Sopko, B., Uher, J., Broz, J., Dolezal, Z., Kodys, P., Tsvetkov, A., Wilhelm, I., Horisberger, R., Rohe, T., Bolla, G., Bortoletto, D., Giolo, K., Miyamoto, J., Rott, C., Roy, A., Shipsey, I., Son, Seunghee, Boisvert, V., Demina, R., Korjenevski, S., Tipton, P., Grillo, A., Metcalfe, J., Sadrozinski, H., Schumm, B., Seiden, A., Spencer, N., Dawson, I., Dervan, P., Werner, A., Sellin, P., Artuso, M., Guskov, J., Marunko, S., Ruzin, A., Tylchin, T., Fasolo, F., Fizzotti, F., Garino, Y., Lo Giudice, A., Manfredotti, C., Olivero, P., Paolini, C., Boscardin, M., Dalla Betta, G. F., Gregori, P., Piemonte, C., Pozza, A., Ronchin, S., Zen, M., Zorzi, N., Escobar, C., Garcia, C., Gonzalez-Sevilla, S., Marti I Garcia, S., Gaubas, E., Jarasiunas, K., Kazlauskiene, V., Kazukauskas, V., Sakalauskas, S., Storasta, J., Sudzius, M., and Vaitkus, J. V.
20. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use
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Polderman, T.J.C., Stefansson, K., Zuccolo, L., Wall, T.L., Stan����kov��, A., Zhan, X., Hunter, D.J., Davila-Velderrain, J., Palviainen, T., Brazel, D.M., 23andMe Research Team, Haller, T., Chen, F., Jiang, Y., Johnson, E.O., Rose, R.J., Martin, N.G., Wedow, R., Rice, J.P., Boehnke, M., Jorgenson, E., Posthuma, D., Haessler, J., Kellis, M., Young, K.A., Jansen, P.R., Bjornsdottir, G., Kardia, S.L.R., Metspalu, A., Chen, C., Eaton, C.B., Madden, P.A.F., Gillespie, N.A., McGue, M., Choquet, H., McMahon, G., Jang, S.-K., Faul, J.D., Nielsen, J.B., Fritsche, L.G., Yin, J., Cucca, F., Medland, S.E., Vrieze, S., Thorgeirsson, T.E., Loukola, A., Reginsson, G.W., Tian, C., Orr��, V., HUNT All-In Psychiatry, Iacono, W.G., Gordon, S.D., Kraft, P., Fiorillo, E., Reiner, A.P., Willer, C.J., Boomsma, D.I., Munaf��, M.R., Tyrfingsson, T., Kaprio, J., Laakso, M., Zajac, G.J.M., Willemsen, G., Hickie, I.B., Runarsdottir, V., Li, Y., Hottenga, J.-J., McQueen, M.B., Ehringer, M.A., Zhou, W., Smith, J.A., Taylor, A.E., Tindle, H.A., Kooperberg, C., Boardman, J.D., Lee, J.J., McGuire, D., Zhao, W., Mulas, A., Cornelis, M.C., Lind, P.A., Hveem, K., Weisner, C., Datta, G., Gudbjartsson, D.F., Lutz, S.M., M��gi, R., Hewitt, J.K., Turman, C., Thai, K.K., Stallings, M.C., Kamatani, Y., Hopfer, C.J., David, S.P., Young, H., Rimm, E., Bierut, L.J., Ling, Y., Foerster, J.R., Harris, K.M., Davies, G.E., Krauter, K.S., Matoba, N., Abecasis, G., Esko, T., Keller, M.C., Whitfield, J.B., Liu, D.J., Huang, H., Stitzel, J.A., Liu, M., Peters, U., Saccone, N.L., Docherty, A.R., Pandit, A., Stefansson, H., Hokanson, J.E., Heath, A.C., Okada, Y., Weir, D.R., and Mohlke, K.L.
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3. Good health - Abstract
Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.
21. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
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Samuel Kuperman, Leila Karhunen, Geòrgia Escaramís, Sébastien Guillaume, Kelly L. Klump, David C. Whiteman, Colin A. Hodgkinson, Stephanie H. Witt, Artemis Tsitsika, Hana Papezova, Renato Polimanti, P. Eline Slagboom, Peter Zill, Jakob Grove, Toni-Kim Clarke, Michael Soyka, Jennifer Jordan, Steven Gallinger, Philip Gorwood, Preben Bo Mortensen, Yuri Milaneschi, Ingrid Meulenbelt, Jen Chyong Wang, Markus M. Nöthen, Katrin Männik, Henry R. Kranzler, Michael M. Vanyukov, Anna Keski-Rahkonen, William G. Iacono, Raymond K. Walters, Stephanie Le Hellard, Bochao Danae Lin, Vesna Boraska Perica, Marion Roberts, Patrick F. Sullivan, Steven Crawford, Mark A. Frye, Melissa A. Munn-Chernoff, Hakon Hakonarson, Andreas Birgegård, Robert Culverhouse, Alexis C. Edwards, Jerome C. Foo, Alessandro Rotondo, Brenda W.J.H. Penninx, Laura M. Hack, Michael T. Lynskey, Mario Maj, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Julie K. O'Toole, Marta Tyszkiewicz-Nwafor, Matt McGue, Julien Bryois, Martina de Zwaan, Norbert Dahmen, Stefanie Heilmann-Heimbach, Deborah Kaminská, Benedetta Nacmias, Nicholas G. Martin, Anna R. Docherty, Christopher Hübel, Nancy L. Pedersen, Janet Treasure, William E. Copeland, Roger A.H. Adan, Jaakko Kaprio, Aarno Palotie, L. John Horwood, Maria La Via, Philippe Courtet, Virpi M. Leppä, Judy L. Silberg, Jason D. Boardman, Fazil Aliev, Wade H. Berrettini, Doo Sup Choi, Youl-Ri Kim, Konstantinos Hatzikotoulas, Harriet de Wit, Sandra A. Brown, Elisabeth Widen, Caroline Hayward, Nicholas J. Schork, Penelope A. Lind, Ralph E. Tarter, Jana Strohmaier, Allan S. Kaplan, Richard A. Grucza, Bradley T. Webb, Angela Favaro, Dalila Pinto, Helena Gaspar, Andrew W. Bergen, Beate Herpertz-Dahlmann, Robert Levitan, Wolfgang Gäbel, Xavier Estivill, Emma C. Johnson, Konstantinos Tziouvas, Lindsay A. Farrer, Lenka Foretova, Marc A. Schuckit, Joanna M. Biernacka, André Scherag, Robbee Wedow, Abraham A. Palmer, Amy E. Adkins, Franziska Degenhardt, Louisa Degenhardt, Jurjen J. Luykx, Marius Lahti-Pulkkinen, Brien P. Riley, Monika Ridinger, Matteo Cassina, Harry Brandt, Yiran Guo, Stephan Ripke, Palmiero Monteleone, Katri Räikkönen, Jonathan R. I. Coleman, Martin A. Kennedy, Stephen W. Scherer, Ioanna Tachmazidou, Catherine M. Olsen, Bernice Porjesz, Esther Walton, Yi-Ling Chou, Nicolas Ramoz, Tetsuya Ando, Andres Metspalu, Bertram Müller-Myhsok, Brion S. Maher, Sarah Bertelsen, Melanie L. Schwandt, Janiece E. DeSocio, Margaret Keyes, John F. Pearson, Dongbing Lai, Paul Lichtenstein, James MacKillop, George Dedoussis, Jari Lahti, Ulrike Schmidt, Stefan Ehrlich, Amanda G. Wills, Teemu Palviainen, David Goldman, Elena Tenconi, Dimitris Dikeos, Scott I. Vrieze, Sietske G. Helder, Katharina Buehren, Hongyu Zhao, Sara McDevitt, Jolanta Lissowska, Joseph M. Boden, Li-Shiun Chen, Susanne Lucae, Sara Marsal, Dan Rujescu, Claes Norring, Howard J. Edenberg, Victor M. Karpyak, Fragiskos Gonidakis, Per Hoffmann, Christopher S. Franklin, Karin Egberts, Johanna Giuranna, Stefan Herms, Leah Wetherill, Stephanie Zerwas, Anthony Batzler, Elliot C. Nelson, Jouke-Jan Hottenga, Marcella Rietschel, Ioanna Ntalla, Victor Hesselbrock, Sarah M. Hartz, Marie Navratilova, Falk Kiefer, Martien J H Kas, Richard J. Rose, Andrew C. Heath, Jin P. Szatkiewicz, Lenka Slachtova, Lisa Lilenfeld, Katherine A. Halmi, John P. Rice, Anjali K. Henders, Christian Dina, Norbert Wodarz, Satu Männistö, Hamdi Mbarek, Shuyang Yao, Vladimir Janout, Alison Goate, Bettina Konte, Alexandra Schosser, Danfeng Chen, Kirsty Kiezebrink, Euijung Ryu, Dana B. Hancock, James Mitchell, Sarah E. Medland, Ina Giegling, Valdo Ricca, Scott D. Gordon, Gabrielle Koller, Samuli Ripatti, Laura M. Thornton, Alison D. Murray, Morten Mattingsdal, Zeynep Yilmaz, Jens Treutlein, Kathleen K. Bucholz, Tim B. Bigdeli, Eric F. van Furth, Hermine H. Maes, Ken B. Hanscombe, Sandra Sanchez-Roige, Daniela Degortes, Monica Forzan, Manuel Mattheisen, Richard Sherva, Scott J. Crow, Mikael Landén, Wolfgang Herzog, Jeanette N. McClintick, Tõnu Esko, Louis Fox, Wolfgang Maier, Liselotte Petersen, Laura J. Bierut, Roseann E. Peterson, Gursharan Kalsi, Kathleen Mullan Harris, Margarita C T Slof-Op 't Landt, Tamara L. Wall, Patrik K. E. Magnusson, Unna N. Danner, Stephan Zipfel, Ulrich W. Preuss, Elisa Docampo, D. Blake Woodside, Alfonso Tortorella, Benjamin W. Domingue, Franziska Ritschel, Johan G. Eriksson, Anu Raevuori, Benjamin M. Neale, Marcus Ising, Annemarie A. van Elburg, Filip Rybakowski, Maureen Reynolds, Tracey D. Wade, Manfred M. Fichter, Monica Gratacos Mayora, Claudette Boni, Andreas J. Forstner, John Whitfield, Silviu Alin Bacanu, Matthew B. McQueen, Andrew M. McIntosh, Norbert Scherbaum, Tatiana Foroud, Gun Peggy Knudsen, Sven Cichon, Christian J. Hopfer, Josef Frank, Eleftheria Zeggini, Federica Tozzi, Nadia Micali, Danielle M. Dick, Pamela A. F. Madden, Christian R. Marshall, Johannes Hebebrand, Fernando Fernández-Aranda, Roel A. Ophoff, Roland Burghardt, Nathaniel Thomas, Leonid Padyukov, Nancy L. Saccone, Anu Loukola, Fabian Streit, James L. Kennedy, Jessica H. Baker, Peter McGuffin, Walter H. Kaye, Pei Hong Shen, Anne Farmer, Roger D. Cone, Ilka Boehm, Jacquelyn L. Meyers, Paolo Santonastaso, Maurizio Clementi, Susana Jiménez-Murcia, Gudrun Wagner, Anke Hinney, Richard Parker, James I. Hudson, Nathan A. Gillespie, Michael Strober, John I. Nurnberger, Sandro Sorbi, Dorret I. Boomsma, Beata Świątkowska, Janne Tidselbak Larsen, Kenneth S. Kendler, Hidetoshi Inoko, Jessica E. Salvatore, Hunna J. Watson, Jochen Seitz, Jacques Pantel, Karl Mann, Hang Zhou, Antonio Julià, Oliver S. P. Davis, Nancy Diazgranados, Krista Fischer, John K. Hewitt, Karen S. Mitchell, Joanna Hauser, Eric O. Johnson, Craig Johnson, E. Jane Costello, Agnieszka Słopień, Dong Li, Laramie E. Duncan, Arpana Agrawal, Grant W. Montgomery, Manuel Föcker, Thomas Werge, Lannie Ligthart, Andreas Karwautz, Raquel Rabionet, Kenneth Krauter, Joel Gelernter, James J. Crowley, Cynthia M. Bulik, Paola Giusti-Rodríguez, Laura M. Huckins, Gerome Breen, Michael C. Stallings, Daniel E. Adkins, Pierre J. Magistretti, John Kramer, Lars Alfredsson, Hartmut Imgart, Annette M. Hartmann, Ole A. Andreassen, Monika Dmitrzak-Weglarz, Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department Psychiatry [Chapel Hill], University of North Carolina System (UNC)-University of North Carolina System (UNC), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], QIMR Berghofer Medical Research Institute, Karolinska Institutet [Stockholm], University Children's Hospital of Essen [Essen, Germany], University of Duisburg-Essen, Aarhus University [Aarhus], Stockholm County Council, University of Würzburg, Guy's Hospital [London], University Medical Center [Utrecht], University of Gothenburg (GU), Altrecht Center for Eating Disorders Rintveld [Zeist, The Netherlands] (Mental Health Institute), National Institute of Mental Health [Tokyo, Japan] (NIMH), National Center of Neurology and Psychiatry [Tokyo, Japan], University of Oslo (UiO), Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Perelman School of Medicine, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Split, The Wellcome Trust Sanger Institute [Cambridge], RWTH Aachen University, Universitätsklinikum Frankfurt, Universita degli Studi di Padova, University Hospital Basel [Basel], Jülich Supercomputing Centre (JSC), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota System, University of Bristol [Bristol], Hannover Medical School [Hannover] (MHH), Harokopio University of Athens, Seattle University [Seattle], Virginia Commonwealth University (VCU), University of Athens Medical School [Athens], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Poznan University of Medical Sciences [Poland] (PUMS), Institute of Environmental Science and Technology [Barcelona] (ICTA), Universitat Autònoma de Barcelona (UAB), Massachusetts General Hospital [Boston], Stanford University, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Estonian Genome and Medicine, University of Tartu, Universitat Pompeu Fabra [Barcelona] (UPF), MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), The Institute of Psychiatry-King‘s College London, Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Ludwig-Maximilians-Universität München (LMU), Infectious diseases division, Department of internal medicine, University of Münster, Masaryk Memorial Cancer Institute, Masaryk Memorial Cancer Institute (RECAMO), Universitätsklinikum Bonn (UKB), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Medstar Research Institute, Universität Duisburg-Essen [Essen], National and Kapodistrian University of Athens (NKUA), Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Psychiatric Genetic Unit, Poznan University of Medical Sciences, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Heidelberg University Hospital [Heidelberg], Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Parkland-Klinik [Bad Wildungen-Reinhardshausen, Germany], Tokai University, Department of Epidemiology and Public Health [university of Ostrava], Lékařská fakulta / Faculty of Medicine [University of Ostrava], Ostravská univerzita / University of Ostrava-Ostravská univerzita / University of Ostrava, Vall d'Hebron University Hospital [Barcelona], Charles University [Prague] (CU), University of Eastern Finland, Medizinische Universität Wien = Medical University of Vienna, Centre de toxicomanie et de santé mentale [Toronto, ON, Canada], University of Helsinki, University of Aberdeen, Faculty of Science, J.E. Purkinje University, J. E. Purkinje University, Michigan State University System, Norwegian Institute of Public Health [Oslo] (NIPH), Haukeland University Hospital, University of Bergen (UiB), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), The Chicago School of Professional Psychology [Washington, District of Columbia, USA] (Washington DC Campus), Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Department of Psychiatry, University of Napoli, Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], University College Cork (UCC), Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, VA Boston Healthcare System, Università degli studi della Campania 'Luigi Vanvitelli', Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kartini Clinic [Portland, Oregon, USA], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Vanderbilt University School of Medicine [Nashville], The Hospital for sick children [Toronto] (SickKids), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Medical Epidemiology and Biostatistics (MEB), University of Pisa - Università di Pisa, Division of Psychiatric Genomics, Institute of Medical Informatics, Biometry and Epidemiology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Leiden University Medical Center (LUMC), Center for Eating Disorders Ursula [Leiden, The Netherlands] (Rivierduinen), Medical University of Łódź (MUL), The Jackson Laboratory [Bar Harbor] (JAX), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Human Genetics, Internal Medicine [Tuebingen, Germany], Tuebingen University [Germany], Oregon Research Institute (ORI), University of Otago [Dunedin, Nouvelle-Zélande], The Center for Eating Disorders at Sheppard Pratt [Baltimore, MD, USA], Weill Medical College of Cornell University [New York], Eating Recovery Center [Denver, CO, USA], Centre for Addiction and Mental Health [Toronto, ON, Canada], University of California [San Diego] (UC San Diego), University of California, Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Institute of Medical Science [Toronto], University of Toronto, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Sahlgrenska Academy at University of Gothenburg [Göteborg], Department of Genomics, Yale University School of Medicine, Indiana University School of Medicine, Indiana University System, Mayo Clinic [Rochester], Mayo Clinic, SUNY Downstate Medical Center, State University of New York (SUNY), University of Edinburgh, Department of Genomics, Life and Brain Center, University of Bonn, University of Utah School of Medicine [Salt Lake City], University of Heidelberg, Medical Faculty, Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], National Institutes of Health [Bethesda] (NIH), National Institute on Alcohol Abuse and Alcoholism [Bethesda, MD, USA] (NIAAA), Martin-Luther-University Halle-Wittenberg, Helsinki Institute of Life Science (HiLIFE), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Vrije Universiteit Amsterdam [Amsterdam] (VU), Mathematical Sciences Institute (MSI), Australian National University (ANU), University of Colorado [Boulder], VU University Medical Center [Amsterdam], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Universität Heidelberg [Heidelberg], Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Harvard University [Cambridge], University of Colorado Anschutz [Aurora], University of Vermont [Burlington], University of New South Wales [Sydney] (UNSW), University of Dusseldorf, Genetics and Pathology, Center for Human Genetic Research, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Heidelberg University, University of Iowa [Iowa City], Vienna University of Technology (TU Wien), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Chronic Disease Epidemiology and Prevention Unit, National Institute for Health and Welfare [Helsinki], Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Indiana University System-Indiana University System, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Regensburg, Rush University Medical Center [Chicago], University of Utah, Duke University Medical Center, University of Illinois [Chicago] (UIC), University of Illinois System, Department of Medical and Molecular Genetics, Dpt of Neuroscience [New York], Laboratory of Neurogenetics, National Institutes of Health [Bethesda] (NIH)-National Institute on Alcohol Abuse and Alcoholism, Department of Health and Human Services, University of Connecticut (UCONN), University of Colorado [Denver], Research Triangle Institute International (RTI International), McMaster University [Hamilton, Ontario], CLinical Psychology, Department of Electrical and Computer Engineering [Montréal], McGill University = Université McGill [Montréal, Canada], Yale School of Public Health (YSPH), Analytic and Translational Genetics Unit, Flinders University [Adelaide, Australia], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Department of Public Health, Indiana University - Purdue University Indianapolis (IUPUI), National Institute of Mental Health (NIMH), University of Pennsylvania, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Università degli Studi di Padova = University of Padua (Unipd), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), King‘s College London-The Institute of Psychiatry, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Masaryk Memorial Cancer Institute (MMCI), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Università degli Studi di Firenze = University of Florence (UniFI), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Medical Research Council-Cardiff University, Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of California (UC), University of California (UC)-University of California (UC), Yale School of Medicine [New Haven, Connecticut] (YSM), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Martinez Rico, Clara, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Kas lab, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), 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., Hubel, C., Gordon, S., Medland, S. E., Watson, H. J., Gaspar, H. A., Bryois, J., Hinney, A., Leppa, V. M., Mattheisen, M., Ripke, S., Yao, S., Giusti-Rodriguez, 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., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Fischer, K., Focker, 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., Jimenez-Murcia, S., Julia, A., Kalsi, G., Kaminska, 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., Swiatkowska, 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., Birgegard, A., Lichtenstein, P., Norring, C., Landen, 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., Gaebel, W., Hayward, C., Ising, M., Keyes, M., Kiefer, F., Koller, G., Kramer, J., Kuperman, S., Lucae, S., Lynskey, M. T., Maier, W., Mann, K., Mannisto, S., Muller-Myhsok, B., Murray, A. D., Nurnberger, J. I., Preuss, U., Raikkonen, 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., Nothen, 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., and Agrawal, A.
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Netherlands Twin Register (NTR) ,Alcoholism/genetics ,Schizophrenia/genetics ,[SDV]Life Sciences [q-bio] ,[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Medizin ,Medicine (miscellaneous) ,Genome-wide association study ,Alcohol use disorder ,Anorexia nervosa ,Linkage Disequilibrium ,ddc:616.89 ,[SCCO]Cognitive science ,0302 clinical medicine ,Risk Factors ,Tobacco Use Disorder/genetics ,Substance-Related Disorders/genetics ,0303 health sciences ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Factors de risc en les malalties ,Bulimia nervosa ,Feeding and Eating Disorders/genetics ,eating disorders ,genetic correlation ,substance use ,Tobacco Use Disorder ,3. Good health ,Fenotip ,[SDV] Life Sciences [q-bio] ,Psychiatry and Mental health ,Alcoholism ,Eating disorders ,Phenotype ,Schizophrenia ,Drinking of alcoholic beverages ,eating disorder ,Consum d'alcohol ,Major depressive disorder ,medicine.symptom ,Depressive Disorder, Major/genetics ,eating disorders, genetic correlation, substance use ,Clinical psychology ,Substance abuse ,Risk factors in diseases ,Substance-Related Disorders ,Polymorphism, Single Nucleotide ,Article ,Feeding and Eating Disorders ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,mental disorders ,Genetics ,medicine ,Humans ,Trastorns de la conducta alimentària ,030304 developmental biology ,Genetic association ,Pharmacology ,Depressive Disorder, Major ,Binge eating ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,[SCCO] Cognitive science ,medicine.disease ,Comorbidity ,Twin study ,030227 psychiatry ,Abús de substàncies ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,business ,Genètica ,030217 neurology & neurosurgery ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Genome-Wide Association Study - 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 (BN) 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 BN 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 (MDD). Total sample sizes per phenotype ranged from ~2,400 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; qwith binge-eating (rg=0.27; q=0.0016). Conversely, significant negative genetic correlations were observed between three non-diagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge-eating (rgs=-0.19 to −0.23; qs
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- 2021
22. Associations of autozygosity with a broad range of human phenotypes
- Author
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Dennis O. Mook-Kanamori, Salma M. Wakil, Lisa R. Yanek, Dominique P.V. de Kleijn, Gert J. de Borst, Alison D. Murray, Kamran Guity, Vincent W. V. Jaddoe, Mario Pirastu, Carole Ober, Giuseppe Matullo, Charles N. Rotimi, Daniela Ruggiero, Teresa Tusié-Luna, Wolfgang Lieb, Chew-Kiat Heng, John R. B. Perry, Hortensia Moreno-Macías, Jie Zhou, John M. Starr, Juhani Junttila, Lei Yu, Danielle Posthuma, Marcus Dörr, Yingchang Lu, Jonathan P. Bradfield, Einat Granot-Hershkovitz, Karina Meidtner, Wouter van Rheenen, T Esko, Maris Alver, Wen-Jane Lee, Zhengming Chen, Jennifer A. Brody, Paolo Gasparini, Yii-Der Ida Chen, Cinzia Sala, Peter P. Pramstaller, Gauri Prasad, Nana Matoba, Natalie Terzikhan, Simonetta Guarrera, Bjarke Feenstra, Peter Vollenweider, Smeeta Shrestha, Yi-Jen Hung, Lilja Stefansdottir, David R. Weir, Felix R. Day, Antonietta Robino, Liang Zhang, Lluis Quintana-Murci, Nicholas J. Timpson, Robyn E Wootton, Xue W. Mei, Dharambir K. Sanghera, Gisli Masson, Debbie A Lawlor, Thomas Meitinger, Sharon L.R. Kardia, Peter K. Joshi, Frank J. A. van Rooij, Claude Bouchard, Cassandra N. Spracklen, Ken K. Ong, Taulant Muka, Guanjie Chen, Laura J. Scott, Walter Palmas, Daniel I. Chasman, Sarah E. Medland, Krista Fischer, Blair H. Smith, Jon K. Sigurdsson, Leon Straker, Clara Viberti, Yuan Shi, Louis Pérusse, Peter J. van der Most, Timo Tõnis Sikka, Chris Haley, Kuang Lin, Leif Groop, Hester M. den Ruijter, Hakon Hakonarson, Masato Akiyama, Stephan J. L. Bakker, Sonja I. Berndt, Jeffery R. O'Connell, Cisca Wijmenga, Daniele Cusi, Lorena Orozco, Kristjan H. S. Moore, Kevin Sandow, Stephen S. Rich, Stephanie J. Loomis, George Davey Smith, Cornelia M. van Duijn, Sharvari Rahul Shukla, Agnar Helgason, Thorsten Kessler, Anuj Goel, Dan Mason, David W. Clark, James S. Pankow, Simona Vaccargiu, Uwe Völker, Tamara B. Harris, Matthew A. Allison, Clicerio Gonzalez, Sarju Ralhan, I-Te Lee, Matthias Laudes, Yen-Feng Chiu, Neil Poulter, Benjamin Lehne, John Wright, Lawrence F. Bielak, Philip L. De Jager, Reinhold Schmidt, Ya Xing Wang, Matthias Nauck, Diana L. Cousminer, Patrick Deelen, Ani Manichaikul, Stephen J. Chanock, Anders Hamsten, Barry I. Freedman, Gudmar Thorleifsson, Peter Kraft, Ozren Polasek, Jie Yao, Yoshinori Murakami, Paul M. Ridker, Anubha Mahajan, Struan F.A. Grant, Claudia Schurmann, Bjarni Gunnarsson, Catriona L. K. Barnes, Jessica van Setten, Sandosh Padmanabhan, Alena Stančáková, Markus M. Lerch, Anuradha Jagadeesan, Franco Giulianini, Daniel F. Gudbjartsson, Dwaipayan Bharadwaj, Shengchao Alfred Li, Peter S. Sever, Trevor A. Mori, Albertine J. Oldehinkel, Koichi Matsuda, Xueling Sim, Evangelos Evangelou, André G. Uitterlinden, Pekka Jousilahti, Yukihide Momozawa, Ioanna Tzoulaki, Chao A. Hsiung, Ginevra Biino, Murielle Bochud, Hannele Mattsson, Ilja M. Nolte, Sarah H. Wild, Patricia B. Munroe, Jianjun Liu, Bruce M. Psaty, Giriraj R. Chandak, Masahiro Kanai, Tony R. Merriman, Teemu Palviainen, Rodney A. Lea, Janie Corley, Nicholas J. Wareham, Alan B. Zonderman, Makoto Hirata, Matthew J. Bixley, Caroline Hayward, Nora Franceschini, Kristel R van Eijk, Etienne Patin, Daniel Shriner, Niek Verweij, Xiuqing Guo, Fredrik Karpe, Ruth J. F. Loos, Tiinamaija Tuomi, Ashley van der Spek, Patricia A. Peyser, Jessica D. Faul, Christian Fuchsberger, David Cesarini, Alex S. F. Doney, Janine F. Felix, Cornelius A. Rietveld, Jagadish Vangipurapu, Tanguy Corre, Line Skotte, Rajkumar Dorajoo, Catherine Igartua, Meena Kumari, Nona Sotoodehnia, Leonard H. van den Berg, Najaf Amin, Dale R. Nyholt, Harry Campbell, Massimiliano Cocca, Scott D. Gordon, Patrik K. E. Magnusson, John C. Chambers, Traci M. Bartz, Mike A. Nalls, Tin Aung, Nduna Dzimiri, Colin N. A. Palmer, Rob M. van Dam, Johanna Kuusisto, Russell P. Tracy, Anna Damulina, Pierre-Emmanuel Morange, Sylvain Foisy, Jing Hua Zhao, Nicholas G. Martin, Ching-Yu Cheng, Mariaelisa Graff, Rashmi B. Prasad, Alice Stanton, David-Alexandre Trégouët, Yu Guo, Helen R. Warren, Lyn R. Griffiths, Weihua Meng, Annika Tillander, Christa Meisinger, Albert V. Smith, Mark I. McCarthy, Jingyun Yang, Marine Germain, Neil Small, Linda Broer, Vilmundur Gudnason, Gunnar K. Pálsson, Michele K. Evans, Alexander Teumer, Mark J. Caulfield, Giorgia Girotto, Thomas Lumley, Tinca J. C. Polderman, Wei Zhao, Carlos A. Aguilar-Salinas, Jari Lahti, Matthew L. Albert, Yechiel Friedlander, Veikko Salomaa, Iona Y Millwood, Jan H. Veldink, Archie Campbell, Andres Metspalu, Ulf Gyllensten, Grant W. Montgomery, Veronique Vitart, Jai Rup Singh, Saima Afaq, Alan R. Shuldiner, Miao-Li Chee, Adebowale Adeyemo, Jennifer A. Smith, David A. van Heel, Jaspal S. Kooner, Daniela Toniolo, Cristian Pattaro, Jerome I. Rotter, John Whitfield, Melissa C. Smart, Kari E. North, Salman M. Tajuddin, Tallapragada Divya Sri Priyanka, Christopher A. Haiman, Diane M. Becker, Bernhard K. Krämer, Paul Elliott, Lihua Wang, He Gao, Patrick Sulem, Jinyan Huang, Chiea Chuen Khor, Ruifang Li-Gao, Åsa Johansson, Winfried März, Shai Carmi, Ilaria Gandin, Eric Boerwinkle, Gardar Sveinbjornsson, Saskia P. Hagenaars, Sander W. van der Laan, Gerard Pasterkamp, E-Shyong Tai, Hagit Hochner, Yih Chung Tham, Kent D. Taylor, Kari Stefansson, Matt J. Neville, Craig E. Pennell, Yanchun Bao, Annelot M. Dekker, Helena Schmidt, Mehdi Hedayati, Joshua Elliott, Ian J. Deary, Iris E. Jansen, Judith B. Borja, Edith Hofer, Martin Gögele, Igor Rudan, Lude Franke, Matthias Munz, Folkert W. Asselbergs, Bengt Sennblad, Imo Hofer, John D. Rioux, Pim van der Harst, Bahareh Sedaghati-khayat, Giovanni Cugliari, Morris A. Swertz, Francine Grodstein, Erwin P. Bottinger, Carol A. Wang, Andre Franke, Brian F. Meyer, Adele M. Taylor, Klodian Dhana, Jian'an Luan, Constance Turman, Robert A. Scott, May E. Montasser, Alison Pattie, Marco Brumat, Liming Li, Heiner Boeing, Karen L. Mohlke, Clemens Baumbach, Bishwa Raj Sapkota, Unnur Thorsteinsdottir, Naveed Sattar, Amy R. Bentley, Matthias B. Schulze, Ivana Kolcic, Stella Trompet, Sarah E. Harris, Ayo P. Doumatey, Charumathi Sabanayagam, David Eccles, Mary F. Feitosa, Jost B. Jonas, Massimo Mezzavilla, Mark O. Goodarzi, David Ellinghaus, Heribert Schunkert, Christian Gieger, Heikki V. Huikuri, Lingyao Zeng, Johan G. Eriksson, Woon-Puay Koh, Yucheng Jia, Gurpreet Singh Wander, James F. Wilson, Torgny Karlsson, Steven C. Hunt, Weihua Zhang, Maria Pina Concas, Zoltán Kutalik, Rebecca Rohde, Chittaranjan S. Yajnik, Yasaman Saba, Dabeeru C. Rao, Robin G. Walters, Reedik Mägi, Marie Loh, Eero Vuoksimaa, Josyf C. Mychaleckyj, Katri Räikkönen, Philippe Goyette, M. Arfan Ikram, Alicia Huerta-Chagoya, David J. Porteous, Teresa Nutile, J. Wouter Jukema, Noha A. Yousri, Yoichiro Kamatani, Maryam S. Daneshpour, Babette S. Zemel, Rona J. Strawbridge, Tien Yin Wong, Claudia Langenberg, Amy Moore, Marcus E. Kleber, Fereidoun Azizi, Avner Halevy, Erika Salvi, Francis S. Collins, Markku Laakso, Tim Kacprowski, S. Sunna Ebenesersdóttir, William R. Scott, Michael Boehnke, Jin-Fang Chai, Markus Perola, Nicola Pirastu, Wayne Huey-Herng Sheu, Robert Karlsson, Lenore J. Launer, Lili Milani, Renée de Mutsert, Fernando Rivadeneira, David A. Bennett, Nicola D. Kerrison, Paolo Manunta, Graciela E. Delgado, Magnus Johannesson, Carolina Medina-Gomez, Alanna C. Morrison, Kay-Tee Khaw, Jian-Min Yuan, Jaakko Kaprio, Melanie Waldenberger, Ralf Ewert, Hugoline G. de Haan, Andrew A. Hicks, Yukinori Okada, Maria Sabater-Lleal, Marilyn C. Cornelis, Stephanie J. London, Federica Rizzi, Jeanette Erdmann, Marina Ciullo, Michiaki Kubo, University of Edinburgh, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Osaka University Graduate School of Medicine, Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE genetics [Reykjavik], Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Area Science Park, Università degli studi di Trieste = University of Trieste, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Harbor UCLA Medical Center [Torrance, Ca.], Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Pop. Genetics, CNR, Sassari, Shardna life science Pula Cagliari, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Medstar Research Institute, Florida State University [Tallahassee] (FSU), University Medical Center [Utrecht], Centre for Population Health Sciences, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), California State University [Sacramento], Department of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Medical University Graz, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Frederick National Laboratory for Cancer Research (FNLCR), Wellcome Trust Centre of Human Genetics, University of Oxford, Department of Epidemiology, German Institute of Human Nutrition, University Medical Center Groningen [Groningen] (UMCG), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Department of Medicine, Surgery, and Dentistry, University of Milano, Icelandic Heart Association, Kopavogur, Iceland., Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Glasgow, Department of Cardiology, Leiden University Medical Center, Leiden, Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, Queen Mary University of London (QMUL), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Genentech, Inc., Genentech, Inc. [San Francisco], University of Tartu, Duke-NUS Medical School [Singapore], Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Human Genome Sequencing Center, Baylor College of Medicine, Baylor College of Medicine (BCM), Baylor University-Baylor University, University of San Carlos, Office of Population Studies Foundation, Icahn School of Medicine at Mount Sinai [New York] (MSSM), King‘s College London, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of Oxford, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, University of Chicago, University of Huddersfield, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Section on Nephrology [Winston-Salem, NC, USA] (Department of Internal Medicine), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, Radcliffe Department of Medicine [Oxford], Harvard School of Public Health, Kunming University of Science and Technology (KMUST), Sans affiliation, University of Southern California (USC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival, University of Cambridge [UK] (CAM), National University of Singapore (NUS), Experimental Cardiology Laboratory (ECL), Unirversity Medical Center, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, Department of Medical Genetics, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Capital Normal University [Beijing], Saw Swee Hock School of Public Health, National Institute for Environmental Health Sciences Research Triangle Park, Brown University, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Toyota Research Institute, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Metacohorts Consortium, Universiteit Leiden, Institute of Clinical Chemistry and Laboratory Medicine, University of Groningen [Groningen], Medical Research Concil Epidemiology Unit, Institute of Medical Science, Faculty of Medicine, Genetics and Pathology, Imperial College London, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Brigham and Women's Hospital [Boston], Erasmus University Rotterdam, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Stockholm Bioinformatics Center (SBC), Stockholm University, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, INRH, Department of Genetics, Los Angeles Biomedical Research Institute (LA BioMed), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Western General Hospital, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Medical Research Council, Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute-University of Pittsburgh Graduate School of Public Health, Zhengzhou University of Light Industry, Department of Electrical and Electronic Engineering [Niigata Univ.], Niigata University, Genetic Epidemiology Unit, University College of London [London] (UCL), Aston Business School, Aston University [Birmingham], Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], Centre Hospitalier Universitaire Vaudois (CHUV), Pennington Biomedical Research Center, University of Washington [Seattle], Guy's and St Thomas' Hospitals, Northwestern Polytechnical University [Xi'an] (NPU), Department of Social Medicine, University of Bristol [Bristol], Department of Genomics of Common Disease [London, UK], Imperial College London-Hammersmith Hospital NHS Imperial College Healthcare, Department of Internal Medicine, Institute of Clinical Molecular Biology, Kiel University, Medizinische Klinik II, Universität zu Lübeck = University of Lübeck [Lübeck], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina, Institute for Social Research, University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Department of Physics, RISSC-Lab-University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Medical Research Center Oulu, University of Oulu, University of Utah School of Medicine [Salt Lake City], The Generation R Study, Pediatrics, Epidemiology, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], Universität Heidelberg [Heidelberg] = Heidelberg University, Interuniversity Cardiology Institute Netherlands, School of Public Health, University of Michigan [Dearborn], Department of Epidemiology and Public Health, University of Kuopio, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institute of Epidemiology and Biobank PopGen, Department of Biostatistics, University of Washington, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Clinical Institute of Medical and Chemical Laboratory Diagnostics, Karl-Franzens-Universität Graz, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), QIMR Berghofer Medical Research Institute, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, University of Illinois [Chicago] (UIC), University of Illinois System, Experimental Cardiology Laboratory, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Functional Genomics, Erasmus Medical Centre, National Human Genome Research Institute (NHGRI), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Pathological Biochemistry, Royal Infirmary, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institute of Metabolic Science, MRC, University of Maryland School of Medicine [Baltimore, MD, USA], Centre for Molecular Epidemiology, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, IRCCS San Raffaele Scientific Institute [Milan, Italie], U937, Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Michigan System, HMNC Brain Health, Singapore Eye Research Institute, Partenaires INRAE, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Groningen, Department of Genomics of Common Disease, Department of Microbiology, The Freeman Hospital, Department Biostatistics University of North Carolina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Clark, D. W., Okada, Y., Moore, K. H. S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C. L. K., Lin, K., Zhao, J. H., Deelen, P., Rohde, R., Schurmann, C., Guo, X., Giulianini, F., Zhang, W., Medina-Gomez, C., Karlsson, R., Bao, Y., Bartz, T. M., Baumbach, C., Biino, G., Bixley, M. J., Brumat, M., Chai, J. -F., Corre, T., Cousminer, D. L., Dekker, A. M., Eccles, D. A., van Eijk, K. R., Fuchsberger, C., Gao, H., Germain, M., Gordon, S. D., de Haan, H. G., Harris, S. E., Hofer, E., Huerta-Chagoya, A., Igartua, C., Jansen, I. E., Jia, Y., Kacprowski, T., Karlsson, T., Kleber, M. E., Li, S. A., Li-Gao, R., Mahajan, A., Matsuda, K., Meidtner, K., Meng, W., Montasser, M. E., van der Most, P. J., Munz, M., Nutile, T., Palviainen, T., Prasad, G., Prasad, R. B., Priyanka, T. D. S., Rizzi, F., Salvi, E., Sapkota, B. R., Shriner, D., Skotte, L., Smart, M. C., Smith, A. V., van der Spek, A., Spracklen, C. N., Strawbridge, R. J., Tajuddin, S. M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H. R., Wootton, R. E., Yanek, L. R., Yao, J., Yousri, N. A., Zhao, W., Adeyemo, A. A., Afaq, S., Aguilar-Salinas, C. A., Akiyama, M., Albert, M. L., Allison, M. A., Alver, M., Aung, T., Azizi, F., Bentley, A. R., Boeing, H., Boerwinkle, E., Borja, J. B., de Borst, G. J., Bottinger, E. P., Broer, L., Campbell, H., Chanock, S., Chee, M. -L., Chen, G., Chen, Y. -D. I., Chen, Z., Chiu, Y. -F., Cocca, M., Collins, F. S., Concas, M. P., Corley, J., Cugliari, G., van Dam, R. M., Damulina, A., Daneshpour, M. S., Day, F. R., Delgado, G. E., Dhana, K., Doney, A. S. F., Dorr, M., Doumatey, A. P., Dzimiri, N., Ebenesersdottir, S. S., Elliott, J., Elliott, P., Ewert, R., Felix, J. F., Fischer, K., Freedman, B. I., Girotto, G., Goel, A., Gogele, M., Goodarzi, M. O., Graff, M., Granot-Hershkovitz, E., Grodstein, F., Guarrera, S., Gudbjartsson, D. F., Guity, K., Gunnarsson, B., Guo, Y., Hagenaars, S. P., Haiman, C. A., Halevy, A., Harris, T. B., Hedayati, M., van Heel, D. A., Hirata, M., Hofer, I., Hsiung, C. A., Huang, J., Hung, Y. -J., Ikram, M. A., Jagadeesan, A., Jousilahti, P., Kamatani, Y., Kanai, M., Kerrison, N. D., Kessler, T., Khaw, K. -T., Khor, C. C., de Kleijn, D. P. V., Koh, W. -P., Kolcic, I., Kraft, P., Kramer, B. K., Kutalik, Z., Kuusisto, J., Langenberg, C., Launer, L. J., Lawlor, D. A., Lee, I. -T., Lee, W. -J., Lerch, M. M., Li, L., Liu, J., Loh, M., London, S. J., Loomis, S., Lu, Y., Luan, J., Magi, R., Manichaikul, A. W., Manunta, P., Masson, G., Matoba, N., Mei, X. W., Meisinger, C., Meitinger, T., Mezzavilla, M., Milani, L., Millwood, I. Y., Momozawa, Y., Moore, A., Morange, P. -E., Moreno-Macias, H., Mori, T. A., Morrison, A. C., Muka, T., Murakami, Y., Murray, A. D., de Mutsert, R., Mychaleckyj, J. C., Nalls, M. A., Nauck, M., Neville, M. J., Nolte, I. M., Ong, K. K., Orozco, L., Padmanabhan, S., Palsson, G., Pankow, J. S., Pattaro, C., Pattie, A., Polasek, O., Poulter, N., Pramstaller, P. P., Quintana-Murci, L., Raikkonen, K., Ralhan, S., Rao, D. C., van Rheenen, W., Rich, S. S., Ridker, P. M., Rietveld, C. A., Robino, A., van Rooij, F. J. A., Ruggiero, D., Saba, Y., Sabanayagam, C., Sabater-Lleal, M., Sala, C. F., Salomaa, V., Sandow, K., Schmidt, H., Scott, L. J., Scott, W. R., Sedaghati-Khayat, B., Sennblad, B., van Setten, J., Sever, P. J., Sheu, W. H. -H., Shi, Y., Shrestha, S., Shukla, S. R., Sigurdsson, J. K., Sikka, T. T., Singh, J. R., Smith, B. H., Stancakova, A., Stanton, A., Starr, J. M., Stefansdottir, L., Straker, L., Sulem, P., Sveinbjornsson, G., Swertz, M. A., Taylor, A. M., Taylor, K. D., Terzikhan, N., Tham, Y. -C., Thorleifsson, G., Thorsteinsdottir, U., Tillander, A., Tracy, R. P., Tusie-Luna, T., Tzoulaki, I., Vaccargiu, S., Vangipurapu, J., Veldink, J. H., Vitart, V., Volker, U., Vuoksimaa, E., Wakil, S. M., Waldenberger, M., Wander, G. S., Wang, Y. X., Wareham, N. 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[0000-0002-8532-5087], Franke, Lude [0000-0002-5159-8802], Haley, Chris S [0000-0002-9811-0210], Hayward, Caroline [0000-0002-9405-9550], Walters, Robin G [0000-0002-9179-0321], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Apollo - University of Cambridge Repository, Moore, Kristjan HS [0000-0002-9579-4362], Luan, Jian'an [0000-0003-3137-6337], Grant, Struan FA [0000-0003-2025-5302], Jaddoe, Vincent WV [0000-0003-2939-0041], Polderman, Tinca JC [0000-0001-5564-301X], Magnusson, Patrik KE [0000-0002-7315-7899], Loos, Ruth JF [0000-0002-8532-5087], Neurology, Human genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Stem Cell Aging Leukemia and Lymphoma (SALL), Institute for Molecular Medicine Finland, Department of Psychology and Logopedics, University Management, Developmental Psychology Research Group, Staff Services, Cognitive and Brain Aging, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Clinicum, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Genetic Epidemiology, Helsinki Collegium for Advanced Studies, HUS Abdominal Center, Endokrinologian yksikkö, Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Trieste, Université de Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], University of Oxford [Oxford], Medical Genetics, Dept. RSD and Public Health, IRCCS-Burlo Garofolo/University of Trieste, sans affiliation, Helmholtz-Zentrum München (HZM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Cardiovascular Science, University College London, Hammersmith Hospital NHS Imperial College Healthcare-Imperial College London, Universität zu Lübeck [Lübeck], University of Ioannina Medical School, Università degli studi di Napoli Federico II-RISSC-Lab, Universität Heidelberg [Heidelberg], University of Turin, University of California-University of California, Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Université de Nantes (UN)-Université de Rennes 1 (UR1), Erasmus MC other, Internal Medicine, and Applied Economics
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0301 basic medicine ,631/208/1397 ,Chemistry(all) ,Health Status ,[SDV]Life Sciences [q-bio] ,LOCI ,General Physics and Astronomy ,MESH: Haplotype ,MESH: Cognition ,030105 genetics & heredity ,Runs of Homozygosity ,Biochemistry ,Consanguinity ,Cognition ,Inbreeding depression ,2.1 Biological and endogenous factors ,Body Size ,Inbreeding ,Skyldleikarækt ,Aetiology ,Human phenotypes ,lcsh:Science ,MESH: Health Status ,Genetics ,Multidisciplinary ,Inbreeding Depression ,Confounding ,Homozygote ,RUNS ,631/208/205 ,631/208/721 ,3. Good health ,genomic inbreeding coefficients ,MESH: Risk-Taking ,631/208/730 ,Autozygosit ,homozygosity ,Erfðarannsóknir ,Medical Genetics ,genomic inbreeding coefficient ,MESH: Homozygote ,Offspring ,Science ,Autozygosity ,Blóðsifjar ,610 Medicine & health ,Biology ,INBREEDING DEPRESSION ,HOMOZYGOSITY ,FERTILITY ,QUANTIFICATION ,Physics and Astronomy(all) ,General Biochemistry, Genetics and Molecular Biology ,Article ,Association ,03 medical and health sciences ,Risk-Taking ,360 Social problems & social services ,Journal Article ,Humans ,ddc:610 ,Allele ,Alleles ,Medicinsk genetik ,Genetic association study ,MESH: Consanguinity ,MESH: Body Size ,MESH: Humans ,Biochemistry, Genetics and Molecular Biology(all) ,MESH: Alleles ,Haplotype ,MESH: Fertility ,General Chemistry ,Brain Disorders ,MESH: Inbreeding Depression ,030104 developmental biology ,Fertility ,Haplotypes ,Genetic markers ,lcsh:Q ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,3111 Biomedicine ,Genetics and Molecular Biology(all) - Abstract
Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.
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- 2019
23. Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling.
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Strom NI, Verhulst B, Bacanu SA, Cheesman R, Purves KL, Gedik H, Mitchell BL, Kwong AS, Faucon AB, Singh K, Medland S, Colodro-Conde L, Krebs K, Hoffmann P, Herms S, Gehlen J, Ripke S, Awasthi S, Palviainen T, Tasanko EM, Peterson RE, Adkins DE, Shabalin AA, Adams MJ, Iveson MH, Campbell A, Thomas LF, Winsvold BS, Drange OK, Børte S, Ter Kuile AR, Nguyen TH, Meier SM, Corfield EC, Hannigan L, Levey DF, Czamara D, Weber H, Choi KW, Pistis G, Couvy-Duchesne B, Van der Auwera S, Teumer A, Karlsson R, Garcia-Argibay M, Lee D, Wang R, Bjerkeset O, Stordal E, Bäckmann J, Salum GA, Zai CC, Kennedy JL, Zai G, Tiwari AK, Heilmann-Heimbach S, Schmidt B, Kaprio J, Kennedy MM, Boden J, Havdahl A, Middeldorp CM, Lopes FL, Akula N, McMahon FJ, Binder EB, Fehm L, Ströhle A, Castelao E, Tiemeier H, Stein DJ, Whiteman D, Olsen C, Fuller Z, Wang X, Wray NR, Byrne EM, Lewis G, Timpson NJ, Davis LK, Hickie IB, Gillespie NA, Milani L, Schumacher J, Woldbye DP, Forstner AJ, Nöthen MM, Hovatta I, Horwood J, Copeland WE, Maes HH, McIntosh AM, Andreassen OA, Zwart JA, Mors O, Børglum AD, Mortensen PB, Ask H, Reichborn-Kjennerud T, Najman JM, Stein MB, Gelernter J, Milaneschi Y, Penninx BW, Boomsma DI, Maron E, Erhardt-Lehmann A, Rück C, Kircher TT, Melzig CA, Alpers GW, Arolt V, Domschke K, Smoller JW, Preisig M, Martin NG, Lupton MK, Luik AI, Reif A, Grabe HJ, Larsson H, Magnusson PK, Oldehinkel AJ, Hartman CA, Breen G, Docherty AR, Coon H, Conrad R, Lehto K, Deckert J, Eley TC, Mattheisen M, and Hettema JM
- Abstract
The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder, and phobias) are highly prevalent, often onset early, persist throughout life, and cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant ANX risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 of the 58 associated variants were replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism, and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism underlying ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies., Competing Interests: Per Hoffmann receives Salary from the Life & Brain GmbH, Bonn, Germany. James L. Kennedy is a member of the Scientific Advisory Board for Myriad Neuroscience Inc. Ian B. Hickie was an inaugural Commissioner on Australia’s National Mental Health Commission (2012-18). He is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 5% equity shareholder in, InnoWell Pty Ltd. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30 M Australian Government-funded Project Synergy (2017-20; a three-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies. Andrew M. Mcintosh has received research support from Eli Lilly, Janssen, and The Sackler Trust. AMM has also received speaker fees from Illumina and Janssen. Murray B. Stein has in the past 3 years received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, Boehringer Ingelheim, Bionomics, BioXcel Therapeutics, Clexio, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He is paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). He has also received research support from NIH, Department of Veterans Affairs, and the Department of Defense. He is on the scientific advisory board for the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America. Joel Gelernter is named as an inventor on PCT patent application #15/878,640 entitled: “Genotype-guided dosing of opioid agonists,” filed January 24, 2018 and issued on January 26, 2021 as U.S. Patent No. 10,900,082; and is paid for editorial work for the journal “Complex Psychiatry.” Iiris Hovatta received speaker’s honoraria from Lundbeck. Ole A. Andreassen received speaker’s honorarium from Lundbeck and Sunovion, consultant for Cortechs.ai and Precision Health AS. Katharina Domschke has been a member of the Steering Committee Neurosciences, Janssen, Inc. until 2022 and is currently a member of the Board of the German National Society of Psychiatry (DGPPN) and the Neurotorium Editorial Board of the Lundbeck Foundation. Jordan W. Smoller is a member of the Scientific Advisory Board of Sensorium Therapeutics (with equity) and has received an honorarium for an internal seminar Tempus Labs. He is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments. Eduard Maron has received research support and has also received speaker fees from Lundbeck. Hans J. Grabe has received travel grants and speakers honoraria from Indorsia, Neuraxpharm, Servier and Janssen Cilag. Henrik Larsson has served as a speaker for Evolan Pharma, Medici and Shire/Takeda and has received research grants from Shire/Takeda; all outside the submitted work. Gerome Breen is an advisory board member for Compass Pathways. Jürgen Deckert is a member of the board of the German Society of Biological Psychiatry and is on the scientific advisory boards of non-profit organizations and foundations. Volker Arolt worked as an advisor for Sanofi-Adventis Germany. Zach Fuller and Xin Wang are employees of 23andMe and hold stock or stock options in 23andMe. All other authors have no competing interests to declare.
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- 2024
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24. Genetic Liability to Cardiovascular Disease, Physical Activity, and Mortality: Findings from the Finnish Twin Cohort.
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Joensuu L, Waller K, Kankaanpää A, Palviainen T, Kaprio J, and Sillanpää E
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- Humans, Female, Finland epidemiology, Middle Aged, Male, Adult, Blood Pressure genetics, Genetic Predisposition to Disease, Longitudinal Studies, Proportional Hazards Models, Twins, Monozygotic, Risk Factors, Cardiovascular Diseases mortality, Cardiovascular Diseases genetics, Exercise
- Abstract
Purpose: We investigated whether longitudinally assessed physical activity (PA) and adherence specifically to World Health Organization PA guidelines mitigate or moderate mortality risk regardless of genetic liability to cardiovascular disease (CVD). We also estimated the causality of the PA-mortality association., Methods: The study used the older Finnish Twin Cohort with 4897 participants aged 33 to 60 yr (54.3% women). Genetic liability to coronary heart disease and systolic and diastolic blood pressure was estimated with polygenic risk scores (PRS) derived from the Pan-UK Biobank ( N ≈ 400,000; >1,000,000 genetic variants). Leisure-time PA was assessed with validated and structured questionnaires three times during 1975 to 1990. The main effects of adherence to PA guidelines and the PRS × PA interactions were evaluated with Cox proportional hazards models against all-cause and CVD mortality. A cotwin control design with 180 monozygotic twin pairs discordant for meeting the guidelines was used for causal inference., Results: During the 17.4-yr (mean) follow-up (85,136 person-years), 1195 participants died, with 389 CVD deaths. PRS (per 1 SD increase) were associated with a 17% to 24% higher CVD mortality risk but not with all-cause mortality except for the PRS for diastolic blood pressure. Adherence to PA guidelines did not show significant independent main effects or interactions with all-cause or CVD mortality. Twins whose activity levels adhered to PA guidelines over a 15-yr period did not have statistically significantly reduced mortality risk compared with their less active identical twin sibling. The findings were similar among high, intermediate, and low genetic risk levels for CVD., Conclusions: The genetically informed Finnish Twin Cohort data could not confirm that adherence to PA guidelines either mitigates or moderates genetic CVD risk or causally reduces mortality risk., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)
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- 2024
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25. TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer's disease.
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Vuoksimaa E, Saari TT, Aaltonen A, Aaltonen S, Herukka SK, Iso-Markku P, Kokkola T, Kyttälä A, Kärkkäinen S, Liedes H, Ollikainen M, Palviainen T, Ruotsalainen I, Toivola A, Urjansson M, Vasankari T, Vähä-Ypyä H, Forsberg MM, Hiltunen M, Jalanko A, Kälviäinen R, Kuopio T, Lähteenmäki J, Nyberg P, Männikkö M, Serpi R, Siltanen S, Palotie A, Kaprio J, Runz H, and Julkunen V
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- Humans, Finland, Female, Aged, Male, Cohort Studies, Middle Aged, Neuropsychological Tests, Cognition, Risk Factors, Research Design, Alzheimer Disease, Biomarkers blood, Biological Specimen Banks
- Abstract
Introduction: A better understanding of the earliest stages of Alzheimer's disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria., Methods and Analysis: A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN., Ethics and Dissemination: This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83., Competing Interests: Competing interests: AP is the Chief Scientific Officer of the FinnGen project that is funded by 13 pharmaceutical companies. HR was a full-time employee of Biogen during study planning and manuscript drafting and has stocks at Merck & Co and Biogen. MMF has received development funding from the Regional Council of Northern Savo and Business Finland for a data-driven tool related to memory disorders and healthcare decision tools, Charles River DRS Finland Ltd. and Orion Pharma have donated equipment for nonclinical cognition testing at the University of Eastern Finland. PI-M has received funding from Orion Research Foundation and Helsinki Biomedicum Foundation outside the present work. RK declares funding paid to the institution from Academy of Finland, 27 Government research funding, Saastamoinen Foundation, Vaajasalo foundation and Jane and Aatos Erkko foundation outside the present work; consulting fees from Orion Pharma; payment or honoraria from Angelini Pharma, Jazz Pharma, Lundbeck, Eisai, Orion Pharma, OmaMedical, Takeda, UCB; participation in monitoring or advisory board from Marinus Pharma and UCB; and leadership or fiduciary role in European Academy of Neurology Epilepsy scientific panel management group, European Epilepsy Reference network Epicare Steering Group and International League Against Epilepsy Career Development Commission. RS declares stocks or stock options at Orion Pharma. S-KH declares payment or honoraria and support for attending meetings or travel from Roche, consulting fees and participation in monitoring or advisory board from Novartis. TK declares payment or honoraria from Novartis Finland and Bayer Nordic SE. The authors declare no other competing financial or non-financial Interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
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- 2024
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26. Genetics of environmental sensitivity to psychiatric and neurodevelopmental phenotypes: evidence from GWAS of monozygotic twins.
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Assary E, Coleman J, Hemani G, van Der Veijer M, Howe L, Palviainen T, Grasby K, Ahlskog R, Nygaard M, Cheesman R, Lim K, Reynolds C, Ordoñana J, Colodro-Conde L, Gordon S, Madrid-Valero J, Thalamuthu A, Hottenga JJ, Mengel-From J, Armstrong NJ, Sachdev P, Lee T, Brodaty H, Trollor J, Wright M, Ames D, Catts V, Latvala A, Vuoksimaa E, Mallard T, Harden K, Tucker-Drob E, Oskarsson S, Hammond C, Christensen K, Taylor M, Lundström S, Larsson H, Karlsson R, Pedersen N, Mather K, Medland S, Boomsma D, Martin N, Plomin R, Bartels M, Lichtenstein P, Kaprio J, Eley T, Davies N, Munroe P, and Keers R
- Abstract
Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, which is more robust to systemic biases that impact population-based methods. We combined data from up to 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct the largest GWAS meta-analysis of monozygotic phenotypic differences in children and adolescents/adults for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder (ADHD) symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism, and wellbeing. The SNP-heritability of variance in these phenotypes were estimated (h2: 0% to 18%), but were imprecise. We identified a total of 13 genome-wide significant associations (SNP, gene, and gene-set), including genes related to stress-reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. Monozygotic twins are an important new source of evidence about the genetics of environmental sensitivity., Competing Interests: Conflicts of interest The authors declare no conflicts of interest.
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- 2024
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27. Genome-Wide Polygenic Score for Muscle Strength Predicts Risk for Common Diseases and Lifespan: A Prospective Cohort Study.
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Herranen P, Koivunen K, Palviainen T, Kujala UM, Ripatti S, Kaprio J, Sillanpää E, and FinnGen
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- Male, Humans, Female, Hand Strength physiology, Prospective Studies, Muscle Strength genetics, Genetic Predisposition to Disease, Longevity, Noncommunicable Diseases
- Abstract
Background: We used a polygenic score for hand grip strength (PGS HGS) to investigate whether genetic predisposition for higher muscle strength predicts age-related noncommunicable diseases, survival from acute adverse health events, and mortality., Methods: This study consisted of 342 443 Finnish biobank participants from FinnGen Data Freeze 10 (53% women) aged 40-108 with combined genotype and health registry data. Associations between PGS HGS and a total of 27 clinical endpoints were explored with linear or Cox regression models., Results: A higher PGS HGS was associated with a reduced risk of selected common noncommunicable diseases and mortality by 2%-10%. The risk for these medical conditions decreased by 5%-23% for participants in the highest PGS HGS quintile compared to those in the lowest PGS HGS quintile. A 1 standard deviation (SD) increase in the PGS HGS predicted a lower body mass index (β = -0.112 kg/m2, standard error [SE] = 0.017, p = 1.69E-11) in women but not in men (β = 0.004 kg/m2, p = .768). PGS HGS was not associated with better survival after acute adverse health events compared to the nondiseased period., Conclusions: The genotype that supports higher muscle strength appears to protect against future health adversities, albeit with modest effect sizes. Further research is needed to investigate whether or how a favorable lifestyle modifies this intrinsic capacity to resist diseases, and if the impacts of lifestyle behavior on health differs due to genetic predisposition for muscle strength., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)
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- 2024
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28. Loci on chromosome 20 interact with rs16969968 to influence cigarettes per day in European ancestry individuals.
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Romero Villela PN, Evans LM, Palviainen T, Border R, Kaprio J, Palmer RHC, Keller MC, and Ehringer MA
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- Humans, Chromosomes, Human, Pair 20, Genetic Predisposition to Disease, Genome-Wide Association Study, Membrane Proteins genetics, Polymorphism, Single Nucleotide genetics, Smoking genetics, South Asian People, United Kingdom, White People, Parkinson Disease, Tobacco Products
- Abstract
Background: The understanding of the molecular genetic contributions to smoking is largely limited to the additive effects of individual single nucleotide polymorphisms (SNPs), but the underlying genetic risk is likely to also include dominance, epistatic, and gene-environment interactions., Methods: To begin to address this complexity, we attempted to identify genetic interactions between rs16969968, the most replicated SNP associated with smoking quantity, and all SNPs and genes across the genome., Results: Using the UK Biobank European subsample, we found one SNP, rs1892967, and two genes, PCNA and TMEM230, that showed a significant genome-wide interaction with rs16969968 for log10 CPD and raw CPD, respectively, in a sample of 116 442 individuals who self-reported currently or previously smoking. We extended these analyses to individuals of South Asian descent and meta-analyzed the combined sample of 117 212 individuals of European and South Asian ancestry. We replicated the gene findings in a meta-analysis of five Finnish samples (N=40 140): FinHealth, FINRISK, Finnish Twin Cohort, GeneRISK, and Health-2000-2011., Conclusions: To our knowledge, this represents the first reliable epistatic association between single nucleotide polymorphisms for smoking behaviors and provides a novel direction for possible future functional studies related to this interaction. Furthermore, this work demonstrates the feasibility of these analyses by pooling multiple datasets across various ancestries, which may be applied to other top SNPs for smoking and/or other phenotypes., Competing Interests: Declaration of Competing Interest Authors report no personal conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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29. Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci.
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Strom NI, Gerring ZF, Galimberti M, Yu D, Halvorsen MW, Abdellaoui A, Rodriguez-Fontenla C, Sealock JM, Bigdeli T, Coleman JR, Mahjani B, Thorp JG, Bey K, Burton CL, Luykx JJ, Zai G, Alemany S, Andre C, Askland KD, Banaj N, Barlassina C, Nissen JB, Bienvenu OJ, Black D, Bloch MH, Boberg J, Børte S, Bosch R, Breen M, Brennan BP, Brentani H, Buxbaum JD, Bybjerg-Grauholm J, Byrne EM, Cabana-Dominguez J, Camarena B, Camarena A, Cappi C, Carracedo A, Casas M, Cavallini MC, Ciullo V, Cook EH, Crosby J, Cullen BA, De Schipper EJ, Delorme R, Djurovic S, Elias JA, Estivill X, Falkenstein MJ, Fundin BT, Garner L, German C, Gironda C, Goes FS, Grados MA, Grove J, Guo W, Haavik J, Hagen K, Harrington K, Havdahl A, Höffler KD, Hounie AG, Hucks D, Hultman C, Janecka M, Jenike E, Karlsson EK, Kelley K, Klawohn J, Krasnow JE, Krebs K, Lange C, Lanzagorta N, Levey D, Lindblad-Toh K, Macciardi F, Maher B, Mathes B, McArthur E, McGregor N, McLaughlin NC, Meier S, Miguel EC, Mulhern M, Nestadt PS, Nurmi EL, O'Connell KS, Osiecki L, Ousdal OT, Palviainen T, Pedersen NL, Piras F, Piras F, Potluri S, Rabionet R, Ramirez A, Rauch S, Reichenberg A, Riddle MA, Ripke S, Rosário MC, Sampaio AS, Schiele MA, Skogholt AH, Sloofman LGSG, Smit J, Soler AM, Thomas LF, Tifft E, Vallada H, van Kirk N, Veenstra-VanderWeele J, Vulink NN, Walker CP, Wang Y, Wendland JR, Winsvold BS, Yao Y, Zhou H, Agrawal A, Alonso P, Berberich G, Bucholz KK, Bulik CM, Cath D, Denys D, Eapen V, Edenberg H, Falkai P, Fernandez TV, Fyer AJ, Gaziano JM, Geller DA, Grabe HJ, Greenberg BD, Hanna GL, Hickie IB, Hougaard DM, Kathmann N, Kennedy J, Lai D, Landén M, Le Hellard S, Leboyer M, Lochner C, McCracken JT, Medland SE, Mortensen PB, Neale BM, Nicolini H, Nordentoft M, Pato M, Pato C, Pauls DL, Piacentini J, Pittenger C, Posthuma D, Ramos-Quiroga JA, Rasmussen SA, Richter MA, Rosenberg DR, Ruhrmann S, Samuels JF, Sandin S, Sandor P, Spalletta G, Stein DJ, Stewart SE, Storch EA, Stranger BE, Turiel M, Werge T, Andreassen OA, Børglum AD, Walitza S, Hveem K, Hansen BK, Rück CP, Martin NG, Milani L, Mors O, Reichborn-Kjennerud T, Ribasés M, Kvale G, Mataix-Cols D, Domschke K, Grünblatt E, Wagner M, Zwart JA, Breen G, Nestadt G, Kaprio J, Arnold PD, Grice DE, Knowles JA, Ask H, Verweij KJ, Davis LK, Smit DJ, Crowley JJ, Scharf JM, Stein MB, Gelernter J, Mathews CA, Derks EM, and Mattheisen M
- Abstract
Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6 , DALRD3 , CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder., Competing Interests: Chris German is employed by and hold stock or stock options in 23andMe, Inc. Erika L. Nurmi is on the Scientific Advisory Board for Myriad Genetics and Medical Advisory Board for Tourette Association of America and received Clinical trial funding from Emalex and Octapharma Pharmaceuticals. Jeremy Veenstra-VanderWeele has served on advisory boards or consulted with Roche, Novartis, and SynapDx; received research funding from Roche, Novartis, SynapDx, Seaside Therapeutics, Forest, Janssen, Acadia, Yamo, and MapLight; received stipends for editorial work from Wiley and Springer. Jens R. Wendland is a current employee and shareholder of Takeda Pharmaceuticals and a past employee and shareholder of F. Hoffmann-La Roche, Pfizer and Nestle Health Science. Cynthia M. Bulik reports: Pearson (author, royalty recipient).Peter Falkai reports no conflict of interest regarding this study and reports to have received financial support and Advisory Board: Richter, Recordati, Boehringer-Ingelheim, Otsuka, Janssen and Lundbeck. Hans J. Grabe has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm, Servier and Janssen Cilag as well as research funding from Fresenius Medical Care. Ian B. Hickie is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney, Australia. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. Professor Hickie has previously led community-based and pharmaceutical industry-supported (Wyeth, Eli Lily, Servier, Pfizer, AstraZeneca, Janssen Cilag) projects focused on the identification and better management of anxiety and depression. He is the Chief Scientific Advisor to, and a 3.2% equity shareholder in, InnoWell Pty Ltd which aims to transform mental health services through the use of innovative technologies. Benjamin M. Neale is a member of the scientific advisory board at Deep Genomics and Neumora. Christopher Pittenger consults and/or receives research support from Biohaven Pharmaceuticals, Freedom Biosciences, Ceruvia Lifesciences, Transcend Therapeutics, UCB BioPharma, and F-Prime Capital Partners. He owns equity in Alco Therapeutics. These relationships are not related to the current work. Dan J. Stein has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda and Vistagen. Eric A. Storch reports receiving research funding to his institution from the Ream Foundation, International OCD Foundation, and NIH. He was formerly a consultant for Brainsway and Biohaven Pharmaceuticals in the past 12 months. He owns stock less than $5000 in NView/Proem for distribution related to the YBOCS scales. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, Routledge, and Jessica Kingsley. Ole A. Andreasson reports to be a consultant to Cortechs.ai, Precision Health AS, speakers honorarium from Otsuka, Lundbeck, Sunovion, Janssen. Anders D. Børglum has received speaker fee from Lundbeck. David Mataix-Cols receives royalties for contributing articles to UpToDate, Wolters Kluwer Health, and personal fees for editorial work from Elsevier, all unrelated to the current work. Murray B. Stein has in the past 3 years received consulting income from Acadia Pharmaceuticals, BigHealth, Biogen, Bionomics, Boehringer Ingelheim, Clexio, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, Otsuka, PureTech Health, Sage Therapeutics, Sumitomo Pharma, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). Joel Gelernter is paid for editorial work by the journal Complex Psychiatry. Pino Alonso has received funding from Biohaven, Boston Scientific, Medtronic. All other authors report no conflicts of interest.
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- 2024
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30. Nightmares share genetic risk factors with sleep and psychiatric traits.
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Ollila HM, Sinnott-Armstrong N, Kantojärvi K, Broberg M, Palviainen T, Jones S, Ripatti V, Pandit A, Rong R, Kristiansson K, Sandman N, Valli K, Hublin C, Ripatti S, Widen E, Kaprio J, Saxena R, and Paunio T
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- Humans, Genome-Wide Association Study, Anxiety Disorders, Risk Factors, Dreams psychology, Sleep Initiation and Maintenance Disorders genetics
- Abstract
Nightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional regulation. Indeed, insomnia, depression, anxiety, or alcohol use have been associated with nightmares in epidemiological and clinical studies. However, the connection between nightmares and their comorbidities are poorly understood. Our goal was to examine the genetic risk factors for nightmares and estimate correlation or causality between nightmares and comorbidities. We performed a genome-wide association study (GWAS) in 45,255 individuals using a questionnaire-based assessment on the frequency of nightmares during the past month and genome-wide genotyping data. While the GWAS did not reveal individual risk variants, heritability was estimated at 5%. In addition, the genetic correlation analysis showed a robust correlation (rg > 0.4) of nightmares with anxiety (rg = 0.671, p = 7.507e-06), depressive (rg = 0.562, p = 1.282e-07) and posttraumatic stress disorders (rg = 0.4083, p = 0.0152), and personality trait neuroticism (rg = 0.667, p = 4.516e-07). Furthermore, Mendelian randomization suggested causality from insomnia to nightmares (beta = 0.027, p = 0.0002). Our findings suggest that nightmares share genetic background with psychiatric traits and that insomnia may increase an individual's liability to experience frequent nightmares. Given the significant correlations with psychiatric and psychological traits, it is essential to grow awareness of how nightmares affect health and disease and systematically collect information about nightmares, especially from clinical samples and larger cohorts., (© 2024. The Author(s).)
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- 2024
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31. Genome-wide association study meta-analysis of dizygotic twinning illuminates genetic regulation of female fecundity.
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Mbarek H, Gordon SD, Duffy DL, Hubers N, Mortlock S, Beck JJ, Hottenga JJ, Pool R, Dolan CV, Actkins KV, Gerring ZF, Van Dongen J, Ehli EA, Iacono WG, Mcgue M, Chasman DI, Gallagher CS, Schilit SLP, Morton CC, Paré G, Willemsen G, Whiteman DC, Olsen CM, Derom C, Vlietinck R, Gudbjartsson D, Cannon-Albright L, Krapohl E, Plomin R, Magnusson PKE, Pedersen NL, Hysi P, Mangino M, Spector TD, Palviainen T, Milaneschi Y, Penninnx BW, Campos AI, Ong KK, Perry JRB, Lambalk CB, Kaprio J, Ólafsson Í, Duroure K, Revenu C, Rentería ME, Yengo L, Davis L, Derks EM, Medland SE, Stefansson H, Stefansson K, Del Bene F, Reversade B, Montgomery GW, Boomsma DI, and Martin NG
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- Animals, Female, Humans, Pregnancy, Carrier Proteins genetics, Hormones, Proteins genetics, United States, Zebrafish genetics, Fertility genetics, Genome-Wide Association Study, Twinning, Dizygotic
- Abstract
Study Question: Which genetic factors regulate female propensity for giving birth to spontaneous dizygotic (DZ) twins?, Summary Answer: We identified four new loci, GNRH1, FSHR, ZFPM1, and IPO8, in addition to previously identified loci, FSHB and SMAD3., What Is Known Already: The propensity to give birth to DZ twins runs in families. Earlier, we reported that FSHB and SMAD3 as associated with DZ twinning and female fertility measures., Study Design, Size, Duration: We conducted a genome-wide association meta-analysis (GWAMA) of mothers of spontaneous dizygotic (DZ) twins (8265 cases, 264 567 controls) and of independent DZ twin offspring (26 252 cases, 417 433 controls)., Participants/materials, Setting, Methods: Over 700 000 mothers of DZ twins, twin individuals and singletons from large cohorts in Australia/New Zealand, Europe, and the USA were carefully screened to exclude twins born after use of ARTs. Genetic association analyses by cohort were followed by meta-analysis, phenome wide association studies (PheWAS), in silico and in vivo annotations, and Zebrafish functional validation., Main Results and the Role of Chance: This study enlarges the sample size considerably from previous efforts, finding four genome-wide significant loci, including two novel signals and a further two novel genes that are implicated by gene level enrichment analyses. The novel loci, GNRH1 and FSHR, have well-established roles in female reproduction whereas ZFPM1 and IPO8 have not previously been implicated in female fertility. We found significant genetic correlations with multiple aspects of female reproduction and body size as well as evidence for significant selection against DZ twinning during human evolution. The 26 top single nucleotide polymorphisms (SNPs) from our GWAMA in European-origin participants weakly predicted the crude twinning rates in 47 non-European populations (r = 0.23 between risk score and population prevalence, s.e. 0.11, 1-tail P = 0.058) indicating that genome-wide association studies (GWAS) are needed in African and Asian populations to explore the causes of their respectively high and low DZ twinning rates. In vivo functional tests in zebrafish for IPO8 validated its essential role in female, but not male, fertility. In most regions, risk SNPs linked to known expression quantitative trait loci (eQTLs). Top SNPs were associated with in vivo reproductive hormone levels with the top pathways including hormone ligand binding receptors and the ovulation cycle., Large Scale Data: The full DZT GWAS summary statistics will made available after publication through the GWAS catalog (https://www.ebi.ac.uk/gwas/)., Limitations, Reasons for Caution: Our study only included European ancestry cohorts. Inclusion of data from Africa (with the highest twining rate) and Asia (with the lowest rate) would illuminate further the biology of twinning and female fertility., Wider Implications of the Findings: About one in 40 babies born in the world is a twin and there is much speculation on why twinning runs in families. We hope our results will inform investigations of ovarian response in new and existing ARTs and the causes of female infertility., Study Funding/competing Interest(s): Support for the Netherlands Twin Register came from the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organization for Health Research and Development (ZonMW) grants, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, 911-09-032, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI.NL, 184.021.007), Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB, European Research Council (ERC-230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1) and the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health and Grand Opportunity grants 1RC2 MH089951. The QIMR Berghofer Medical Research Institute (QIMR) study was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498, 1050208, 1075175). L.Y. is funded by Australian Research Council (Grant number DE200100425). The Minnesota Center for Twin and Family Research (MCTFR) was supported in part by USPHS Grants from the National Institute on Alcohol Abuse and Alcoholism (AA09367 and AA11886) and the National Institute on Drug Abuse (DA05147, DA13240, and DA024417). The Women's Genome Health Study (WGHS) was funded by the National Heart, Lung, and Blood Institute (HL043851 and HL080467) and the National Cancer Institute (CA047988 and UM1CA182913), with support for genotyping provided by Amgen. Data collection in the Finnish Twin Registry has been supported by the Wellcome Trust Sanger Institute, the Broad Institute, ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement number 201413, National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, AA-09203, AA15416, and K02AA018755) and the Academy of Finland (grants 100499, 205585, 118555, 141054, 264146, 308248, 312073 and 336823 to J. Kaprio). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. For NESDA, funding was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10000-1002), the Center for Medical Systems Biology (CSMB, NVVO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University's Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, ROI D0042157-01A, MH081802, Grand Opportunity grants 1 RC2 Ml-1089951 and IRC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. Work in the Del Bene lab was supported by the Programme Investissements d'Avenir IHU FOReSIGHT (ANR-18-IAHU-01). C.R. was supported by an EU Horizon 2020 Marie Skłodowska-Curie Action fellowship (H2020-MSCA-IF-2014 #661527). H.S. and K.S. are employees of deCODE Genetics/Amgen. The other authors declare no competing financial interests., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)
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- 2024
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32. Polygenic risk of obesity and BMI trajectories over 36 years: A longitudinal study of adult Finnish twins.
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Berntzen BJ, Palviainen T, Silventoinen K, Pietiläinen KH, and Kaprio J
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- Adult, Humans, Body Mass Index, Finland epidemiology, Longitudinal Studies, Male, Female, Obesity epidemiology, Obesity genetics, Twins, Dizygotic genetics, Twins, Monozygotic genetics
- Abstract
Objective: This study investigated 36-year BMI trajectories in twins whose BMI in young adulthood was below, within, or above their genetically predicted BMI, with a focus on twin pairs with large intrapair BMI differences (within-pair ΔBMI ≥ 3 kg/m
2 )., Methods: Together, 3227 like-sexed twin pairs (34% monozygotic) were examined at age ~30 years in 1975 and followed up in 1981, 1990, and 2011. An individual's observed BMI in 1975 was considered within (±2.0), below (<-2.0), or above (>+2.0) genetically predicted BMI, measured by a polygenic risk score of 996,919 single nucleotide polymorphisms., Results: In monozygotic and dizygotic twin pairs with large intrapair BMI differences, the co-twin with a higher observed BMI in 1975 deviated above predicted BMI more frequently (~2/3) than the co-twin with a lower BMI deviated below prediction (~1/3). Individuals below, within, and above prediction in 1975 reached, respectively, normal weight, overweight, and obesity by 2011, with a mean BMI increase of 4.5 (95% CI: 4.3-4.8)., Conclusions: Categorizing BMI as below, within, or above polygenic risk score-predicted BMI helps identifying individuals who have been resistant or susceptible to weight gain. This may provide new insights into determinants and consequences of obesity., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)- Published
- 2023
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33. TWINGEN - protocol for an observational clinical biobank recall and biomarker study to identify individuals with high risk of Alzheimer's disease.
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Vuoksimaa E, Saari TT, Aaltonen A, Aaltonen S, Herukka SK, Iso-Markku P, Kokkola T, Kyttälä A, Kärkkäinen S, Liedes H, Ollikainen M, Palviainen T, Ruotsalainen I, Toivola A, Urjansson M, Vasankari T, Vähä-Ypyä H, Forsberg MM, Hiltunen M, Jalanko A, Kälviäinen R, Kuopio T, Lähteenmäki J, Nyberg P, Männikkö M, Serpi R, Siltanen S, Palotie A, Kaprio J, Runz H, and Julkunen V
- Abstract
Introduction: A better understanding of the earliest stages of Alzheimer's disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among Finnish biobank donors according to TWINGEN study criteria., Methods and Analysis: A multi-center study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behavior and sleep. A sub-cohort are being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. TWINGEN data will be transferred to Finnish Institute of Health and Welfare (THL) biobank and we aim to further to transfer it to the FinnGen study where it will be combined with health registry data for prediction of AD., Ethics and Dissemination: This recall study consists of FTC/THL/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83., Competing Interests: Competing interests statement AP is the Chief Scientific Officer of the FinnGen project that is funded by thirteen pharmaceutical companies. HR was a full-time employee of Biogen during study planning and manuscript drafting and has stocks at Merck & Co. and Biogen Inc. MMF has received development funding from the Regional Council of Northern Savo and Business Finland for a data-driven tool related to memory disorders and healthcare decision tools, Charles River DRS Finland Ltd. and Orion Pharma have donated equipment for nonclinical cognition testing at the University of Eastern Finland. PI-M has received funding from Orion Research Foundation and Helsinki Biomedicum Foundation outside the present work. RK declares funding paid to the institution from Academy of Finland, Government research funding, Saastamoinen Foundation, Vaajasalo foundation and Jane and Aatos Erkko foundation outside the present work; consulting fees from Orion Pharma; payment or honoraria from Angelini Pharma, Jazz Pharma, Lundbeck, Eisai, Orion Pharma, OmaMedical, Takeda, UCB; participation in monitoring or advisory board from Marinus Pharma and UCB; and leadership or fiduciary role in European Academy of Neurology Epilepsy scientific panel management group, European Epilepsy Reference network Epicare Steering Group and International League Against Epilepsy Career Development Commission. RS declares stocks or stock options at Orion Pharma. S-KH declares payment or honoraria and support for attending meetings or travel from Roche, consulting fees and participation in monitoring or advisory board from Novartis. TK declares payment or honoraria from Novartis Finland and Bayer Nordic SE. The authors declare no other competing financial or non-financial Interests.
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- 2023
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34. Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.
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Shrine N, Izquierdo AG, Chen J, Packer R, Hall RJ, Guyatt AL, Batini C, Thompson RJ, Pavuluri C, Malik V, Hobbs BD, Moll M, Kim W, Tal-Singer R, Bakke P, Fawcett KA, John C, Coley K, Piga NN, Pozarickij A, Lin K, Millwood IY, Chen Z, Li L, Wijnant SRA, Lahousse L, Brusselle G, Uitterlinden AG, Manichaikul A, Oelsner EC, Rich SS, Barr RG, Kerr SM, Vitart V, Brown MR, Wielscher M, Imboden M, Jeong A, Bartz TM, Gharib SA, Flexeder C, Karrasch S, Gieger C, Peters A, Stubbe B, Hu X, Ortega VE, Meyers DA, Bleecker ER, Gabriel SB, Gupta N, Smith AV, Luan J, Zhao JH, Hansen AF, Langhammer A, Willer C, Bhatta L, Porteous D, Smith BH, Campbell A, Sofer T, Lee J, Daviglus ML, Yu B, Lim E, Xu H, O'Connor GT, Thareja G, Albagha OME, Suhre K, Granell R, Faquih TO, Hiemstra PS, Slats AM, Mullin BH, Hui J, James A, Beilby J, Patasova K, Hysi P, Koskela JT, Wyss AB, Jin J, Sikdar S, Lee M, May-Wilson S, Pirastu N, Kentistou KA, Joshi PK, Timmers PRHJ, Williams AT, Free RC, Wang X, Morrison JL, Gilliland FD, Chen Z, Wang CA, Foong RE, Harris SE, Taylor A, Redmond P, Cook JP, Mahajan A, Lind L, Palviainen T, Lehtimäki T, Raitakari OT, Kaprio J, Rantanen T, Pietiläinen KH, Cox SR, Pennell CE, Hall GL, Gauderman WJ, Brightling C, Wilson JF, Vasankari T, Laitinen T, Salomaa V, Mook-Kanamori DO, Timpson NJ, Zeggini E, Dupuis J, Hayward C, Brumpton B, Langenberg C, Weiss S, Homuth G, Schmidt CO, Probst-Hensch N, Jarvelin MR, Morrison AC, Polasek O, Rudan I, Lee JH, Sayers I, Rawlins EL, Dudbridge F, Silverman EK, Strachan DP, Walters RG, Morris AP, London SJ, Cho MH, Wain LV, Hall IP, and Tobin MD
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- 2023
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35. Associations of polygenic inheritance of physical activity with aerobic fitness, cardiometabolic risk factors and diseases: the HUNT study.
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Tynkkynen NP, Törmäkangas T, Palviainen T, Hyvärinen M, Klevjer M, Joensuu L, Kujala U, Kaprio J, Bye A, and Sillanpää E
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- Humans, Diabetes Mellitus, Type 2, Hypertension, Multifactorial Inheritance, Cardiometabolic Risk Factors, Exercise, Genetic Risk Score
- Abstract
Physical activity (PA), aerobic fitness, and cardiometabolic diseases (CMD) are highly heritable multifactorial phenotypes. Shared genetic factors may underlie the associations between higher levels of PA and better aerobic fitness and a lower risk for CMDs. We aimed to study how PA genotype associates with self-reported PA, aerobic fitness, cardiometabolic risk factors and diseases. PA genotype, which combined variation in over one million of gene variants, was composed using the SBayesR polygenic scoring methodology. First, we constructed a polygenic risk score for PA in the Trøndelag Health Study (N = 47,148) using UK Biobank single nucleotide polymorphism-specific weights (N = 400,124). The associations of the PA PRS and continuous variables were analysed using linear regression models and with CMD incidences using Cox proportional hazard models. The results showed that genotypes predisposing to higher amount of PA were associated with greater self-reported PA (Beta [B] = 0.282 MET-h/wk per SD of PRS for PA, 95% confidence interval [CI] = 0.211, 0.354) but not with aerobic fitness. These genotypes were also associated with healthier cardiometabolic profile (waist circumference [B = -0.003 cm, 95% CI = -0.004, -0.002], body mass index [B = -0.002 kg/m
2 , 95% CI = -0.004, -0.001], high-density lipoprotein cholesterol [B = 0.004 mmol/L, 95% CI = 0.002, 0.006]) and lower incidence of hypertensive diseases (Hazard Ratio [HR] = 0.97, 95% CI = 0.951, 0.990), stroke (HR = 0.94, 95% CI = 0.903, 0.978) and type 2 diabetes (HR = 0.94, 95 % CI = 0.902, 0.970). Observed associations were independent of self-reported PA. These results support earlier findings suggesting small pleiotropic effects between PA and CMDs and provide new evidence about associations of polygenic inheritance of PA and intermediate cardiometabolic risk factors., (© 2023. The Author(s).)- Published
- 2023
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36. Perceived Occupational Noise Exposure and Depression in Young Finnish Adults.
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Heinonen-Guzejev M, Whipp AM, Wang Z, Ranjit A, Palviainen T, van Kamp I, and Kaprio J
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- Finland epidemiology, Depression epidemiology, Depression diagnosis, Longitudinal Studies, Noise, Occupational adverse effects, Occupational Exposure
- Abstract
We investigated the association between perceived occupational noise exposure and depressive symptoms in young Finnish adults and whether noise sensitivity moderates this association. This study was based on an ongoing longitudinal twin study. We included those who had been working daily ( n = 521) or weekly ( n = 245) during the past 12 months (mean age 22.4, SD 0.7, 53% female). We asked about occupational noise exposure at age 22 and assessed depressive symptoms using the General Behavior Inventory (GBI) at age 17 and 22. Noise sensitivity and covariates were used in linear regression models. Perceived daily occupational noise exposure was associated, as a statistically independent main effect with depressive symptoms at age 22 (beta 1.19; 95% CI 0.09, 2.29) among all, and separately for females (beta 2.22; 95% CI 0.34, 4.09) but not males (beta 0.22; 95% CI -1.08, 1.52). Noise sensitivity was independently associated with depressive symptoms among all (beta 1.35; 95% CI 0.54, 2.17), and separately for males (beta 1.96; 95% CI 0.68, 3.24) but not females (beta 1.05; 95 % CI -0.04, 2.13). Noise sensitivity was independent of perceived occupational noise exposure. Pre-existing depressive symptoms at age 17 were predictive of perceived occupational noise exposure, suggesting complex interactions of noise and depression.
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- 2023
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37. Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.
- Author
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Shrine N, Izquierdo AG, Chen J, Packer R, Hall RJ, Guyatt AL, Batini C, Thompson RJ, Pavuluri C, Malik V, Hobbs BD, Moll M, Kim W, Tal-Singer R, Bakke P, Fawcett KA, John C, Coley K, Piga NN, Pozarickij A, Lin K, Millwood IY, Chen Z, Li L, Wijnant SRA, Lahousse L, Brusselle G, Uitterlinden AG, Manichaikul A, Oelsner EC, Rich SS, Barr RG, Kerr SM, Vitart V, Brown MR, Wielscher M, Imboden M, Jeong A, Bartz TM, Gharib SA, Flexeder C, Karrasch S, Gieger C, Peters A, Stubbe B, Hu X, Ortega VE, Meyers DA, Bleecker ER, Gabriel SB, Gupta N, Smith AV, Luan J, Zhao JH, Hansen AF, Langhammer A, Willer C, Bhatta L, Porteous D, Smith BH, Campbell A, Sofer T, Lee J, Daviglus ML, Yu B, Lim E, Xu H, O'Connor GT, Thareja G, Albagha OME, Suhre K, Granell R, Faquih TO, Hiemstra PS, Slats AM, Mullin BH, Hui J, James A, Beilby J, Patasova K, Hysi P, Koskela JT, Wyss AB, Jin J, Sikdar S, Lee M, May-Wilson S, Pirastu N, Kentistou KA, Joshi PK, Timmers PRHJ, Williams AT, Free RC, Wang X, Morrison JL, Gilliland FD, Chen Z, Wang CA, Foong RE, Harris SE, Taylor A, Redmond P, Cook JP, Mahajan A, Lind L, Palviainen T, Lehtimäki T, Raitakari OT, Kaprio J, Rantanen T, Pietiläinen KH, Cox SR, Pennell CE, Hall GL, Gauderman WJ, Brightling C, Wilson JF, Vasankari T, Laitinen T, Salomaa V, Mook-Kanamori DO, Timpson NJ, Zeggini E, Dupuis J, Hayward C, Brumpton B, Langenberg C, Weiss S, Homuth G, Schmidt CO, Probst-Hensch N, Jarvelin MR, Morrison AC, Polasek O, Rudan I, Lee JH, Sayers I, Rawlins EL, Dudbridge F, Silverman EK, Strachan DP, Walters RG, Morris AP, London SJ, Cho MH, Wain LV, Hall IP, and Tobin MD
- Subjects
- Humans, Genome-Wide Association Study, Genetic Predisposition to Disease genetics, Smoking adverse effects, Smoking genetics, Polymorphism, Single Nucleotide genetics, Lung, Pulmonary Disease, Chronic Obstructive genetics
- Abstract
Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies., (© 2023. The Author(s).)
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- 2023
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38. Genetic diversity fuels gene discovery for tobacco and alcohol use.
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Saunders GRB, Wang X, Chen F, Jang SK, Liu M, Wang C, Gao S, Jiang Y, Khunsriraksakul C, Otto JM, Addison C, Akiyama M, Albert CM, Aliev F, Alonso A, Arnett DK, Ashley-Koch AE, Ashrani AA, Barnes KC, Barr RG, Bartz TM, Becker DM, Bielak LF, Benjamin EJ, Bis JC, Bjornsdottir G, Blangero J, Bleecker ER, Boardman JD, Boerwinkle E, Boomsma DI, Boorgula MP, Bowden DW, Brody JA, Cade BE, Chasman DI, Chavan S, Chen YI, Chen Z, Cheng I, Cho MH, Choquet H, Cole JW, Cornelis MC, Cucca F, Curran JE, de Andrade M, Dick DM, Docherty AR, Duggirala R, Eaton CB, Ehringer MA, Esko T, Faul JD, Fernandes Silva L, Fiorillo E, Fornage M, Freedman BI, Gabrielsen ME, Garrett ME, Gharib SA, Gieger C, Gillespie N, Glahn DC, Gordon SD, Gu CC, Gu D, Gudbjartsson DF, Guo X, Haessler J, Hall ME, Haller T, Harris KM, He J, Herd P, Hewitt JK, Hickie I, Hidalgo B, Hokanson JE, Hopfer C, Hottenga J, Hou L, Huang H, Hung YJ, Hunter DJ, Hveem K, Hwang SJ, Hwu CM, Iacono W, Irvin MR, Jee YH, Johnson EO, Joo YY, Jorgenson E, Justice AE, Kamatani Y, Kaplan RC, Kaprio J, Kardia SLR, Keller MC, Kelly TN, Kooperberg C, Korhonen T, Kraft P, Krauter K, Kuusisto J, Laakso M, Lasky-Su J, Lee WJ, Lee JJ, Levy D, Li L, Li K, Li Y, Lin K, Lind PA, Liu C, Lloyd-Jones DM, Lutz SM, Ma J, Mägi R, Manichaikul A, Martin NG, Mathur R, Matoba N, McArdle PF, McGue M, McQueen MB, Medland SE, Metspalu A, Meyers DA, Millwood IY, Mitchell BD, Mohlke KL, Moll M, Montasser ME, Morrison AC, Mulas A, Nielsen JB, North KE, Oelsner EC, Okada Y, Orrù V, Palmer ND, Palviainen T, Pandit A, Park SL, Peters U, Peters A, Peyser PA, Polderman TJC, Rafaels N, Redline S, Reed RM, Reiner AP, Rice JP, Rich SS, Richmond NE, Roan C, Rotter JI, Rueschman MN, Runarsdottir V, Saccone NL, Schwartz DA, Shadyab AH, Shi J, Shringarpure SS, Sicinski K, Skogholt AH, Smith JA, Smith NL, Sotoodehnia N, Stallings MC, Stefansson H, Stefansson K, Stitzel JA, Sun X, Syed M, Tal-Singer R, Taylor AE, Taylor KD, Telen MJ, Thai KK, Tiwari H, Turman C, Tyrfingsson T, Wall TL, Walters RG, Weir DR, Weiss ST, White WB, Whitfield JB, Wiggins KL, Willemsen G, Willer CJ, Winsvold BS, Xu H, Yanek LR, Yin J, Young KL, Young KA, Yu B, Zhao W, Zhou W, Zöllner S, Zuccolo L, Batini C, Bergen AW, Bierut LJ, David SP, Gagliano Taliun SA, Hancock DB, Jiang B, Munafò MR, Thorgeirsson TE, Liu DJ, and Vrieze S
- Subjects
- Humans, Genome-Wide Association Study methods, Risk Factors, Transcriptome, Sample Size, Genetic Loci genetics, Europe ethnology, Genetic Predisposition to Disease genetics, Genetic Variation genetics, Multifactorial Inheritance genetics, Tobacco Use genetics, Alcohol Drinking genetics, Internationality
- Abstract
Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury
1-4 . These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5 . Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction., (© 2022. The Author(s).)- Published
- 2022
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39. A Polygenic Risk Score for Hand Grip Strength Predicts Muscle Strength and Proximal and Distal Functional Outcomes among Older Women.
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Herranen P, Palviainen T, Rantanen T, Tiainen K, Viljanen A, Kaprio J, and Sillanpää E
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- Aged, Aging physiology, Female, Humans, Muscle Strength genetics, Risk Factors, Activities of Daily Living, Hand Strength physiology
- Abstract
Purpose: Hand grip strength (HGS) is a widely used indicator of overall muscle strength and general health. We computed a polygenic risk score (PRS) for HGS and examined whether it predicted muscle strength, functional capacity, and disability outcomes., Methods: Genomewide association study summary statistics for HGS from the Pan-UK Biobank was used. PRS were calculated in the Finnish Twin Study on Aging ( N = 429 women, 63-76 yr). Strength tests included HGS, isometric knee extension, and ankle plantarflexion strength. Functional capacity was examined with the Timed Up and Go, 6-min and 10-m walk tests, and dual-task tests. Disabilities in the basic activities of daily living (ADL) and instrumental ADL (IADL) were investigated with questionnaires. The proportion of variation in outcomes accounted for by PRS HGS was examined using linear mixed models and extended logistic regression., Results: The measured HGS increased linearly over increasing PRS ( β = 4.8, SE = 0.93, P < 0.001). PRS HGS independently accounted for 6.1% of the variation in the measured HGS ( β = 14.2, SE = 3.1, P < 0.001), 5.4% of the variation in knee extension strength ( β = 19.6, SE = 4.7, P < 0.001), 1.2% of the variation in ankle plantarflexion strength ( β = 9.4, SE = 4.2, P = 0.027), and 0.1%-1.5% of the variation in functional capacity tests ( P = 0.016-0.133). Further, participants with higher PRS HGS were less likely to have ADL/IADL disabilities (odds ratio = 0.74-0.76)., Conclusions: Older women with genetic risk for low muscle strength were significantly weaker than those with genetic susceptibility for high muscle strength. PRS HGS was also systematically associated with overall muscle strength and proximal and distal functional outcomes that require muscle strength., (Copyright © 2022 by the American College of Sports Medicine.)
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- 2022
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40. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.
- Author
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Tielbeek JJ, Uffelmann E, Williams BS, Colodro-Conde L, Gagnon É, Mallard TT, Levitt BE, Jansen PR, Johansson A, Sallis HM, Pistis G, Saunders GRB, Allegrini AG, Rimfeld K, Konte B, Klein M, Hartmann AM, Salvatore JE, Nolte IM, Demontis D, Malmberg ALK, Burt SA, Savage JE, Sugden K, Poulton R, Harris KM, Vrieze S, McGue M, Iacono WG, Mota NR, Mill J, Viana JF, Mitchell BL, Morosoli JJ, Andlauer TFM, Ouellet-Morin I, Tremblay RE, Côté SM, Gouin JP, Brendgen MR, Dionne G, Vitaro F, Lupton MK, Martin NG, Castelao E, Räikkönen K, Eriksson JG, Lahti J, Hartman CA, Oldehinkel AJ, Snieder H, Liu H, Preisig M, Whipp A, Vuoksimaa E, Lu Y, Jern P, Rujescu D, Giegling I, Palviainen T, Kaprio J, Harden KP, Munafò MR, Morneau-Vaillancourt G, Plomin R, Viding E, Boutwell BB, Aliev F, Dick DM, Popma A, Faraone SV, Børglum AD, Medland SE, Franke B, Boivin M, Pingault JB, Glennon JC, Barnes JC, Fisher SE, Moffitt TE, Caspi A, Polderman TJC, and Posthuma D
- Subjects
- Animals, Mice, Genome-Wide Association Study, Aggression psychology, Multifactorial Inheritance genetics, Membrane Proteins genetics, Nerve Tissue Proteins genetics, Antisocial Personality Disorder genetics, Conduct Disorder genetics, Conduct Disorder psychology
- Abstract
Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10
-10 ). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg = -0.58, father's age at death rg = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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41. A genome-wide association study of total child psychiatric problems scores.
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Neumann A, Nolte IM, Pappa I, Ahluwalia TS, Pettersson E, Rodriguez A, Whitehouse A, van Beijsterveldt CEM, Benyamin B, Hammerschlag AR, Helmer Q, Karhunen V, Krapohl E, Lu Y, van der Most PJ, Palviainen T, St Pourcain B, Seppälä I, Suarez A, Vilor-Tejedor N, Tiesler CMT, Wang C, Wills A, Zhou A, Alemany S, Bisgaard H, Bønnelykke K, Davies GE, Hakulinen C, Henders AK, Hyppönen E, Stokholm J, Bartels M, Hottenga JJ, Heinrich J, Hewitt J, Keltikangas-Järvinen L, Korhonen T, Kaprio J, Lahti J, Lahti-Pulkkinen M, Lehtimäki T, Middeldorp CM, Najman JM, Pennell C, Power C, Oldehinkel AJ, Plomin R, Räikkönen K, Raitakari OT, Rimfeld K, Sass L, Snieder H, Standl M, Sunyer J, Williams GM, Bakermans-Kranenburg MJ, Boomsma DI, van IJzendoorn MH, Hartman CA, and Tiemeier H
- Subjects
- Genetic Predisposition to Disease, Genome-Wide Association Study methods, Humans, Polymorphism, Single Nucleotide, Attention Deficit Disorder with Hyperactivity genetics, Attention Deficit Disorder with Hyperactivity psychology, Bipolar Disorder genetics
- Abstract
Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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42. Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms.
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Jami ES, Hammerschlag AR, Ip HF, Allegrini AG, Benyamin B, Border R, Diemer EW, Jiang C, Karhunen V, Lu Y, Lu Q, Mallard TT, Mishra PP, Nolte IM, Palviainen T, Peterson RE, Sallis HM, Shabalin AA, Tate AE, Thiering E, Vilor-Tejedor N, Wang C, Zhou A, Adkins DE, Alemany S, Ask H, Chen Q, Corley RP, Ehli EA, Evans LM, Havdahl A, Hagenbeek FA, Hakulinen C, Henders AK, Hottenga JJ, Korhonen T, Mamun A, Marrington S, Neumann A, Rimfeld K, Rivadeneira F, Silberg JL, van Beijsterveldt CE, Vuoksimaa E, Whipp AM, Tong X, Andreassen OA, Boomsma DI, Brown SA, Burt SA, Copeland W, Dick DM, Harden KP, Harris KM, Hartman CA, Heinrich J, Hewitt JK, Hopfer C, Hypponen E, Jarvelin MR, Kaprio J, Keltikangas-Järvinen L, Klump KL, Krauter K, Kuja-Halkola R, Larsson H, Lehtimäki T, Lichtenstein P, Lundström S, Maes HH, Magnus P, Munafò MR, Najman JM, Njølstad PR, Oldehinkel AJ, Pennell CE, Plomin R, Reichborn-Kjennerud T, Reynolds C, Rose RJ, Smolen A, Snieder H, Stallings M, Standl M, Sunyer J, Tiemeier H, Wadsworth SJ, Wall TL, Whitehouse AJO, Williams GM, Ystrøm E, Nivard MG, Bartels M, and Middeldorp CM
- Subjects
- Adolescent, Adult, Aggression, Anxiety genetics, Bipolar Disorder, Child, Child, Preschool, Depression genetics, Humans, Loneliness, Polymorphism, Single Nucleotide, Schizophrenia, Attention Deficit Disorder with Hyperactivity genetics, Autistic Disorder genetics, Genome-Wide Association Study, Sleep Initiation and Maintenance Disorders genetics
- Abstract
Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence., Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument., Results: The meta-analysis of overall internalizing symptoms (INT
overall ) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg | > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg | = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa., Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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43. Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss.
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Trpchevska N, Freidin MB, Broer L, Oosterloo BC, Yao S, Zhou Y, Vona B, Bishop C, Bizaki-Vallaskangas A, Canlon B, Castellana F, Chasman DI, Cherny S, Christensen K, Concas MP, Correa A, Elkon R, Mengel-From J, Gao Y, Giersch ABS, Girotto G, Gudjonsson A, Gudnason V, Heard-Costa NL, Hertzano R, Hjelmborg JVB, Hjerling-Leffler J, Hoffman HJ, Kaprio J, Kettunen J, Krebs K, Kähler AK, Lallemend F, Launer LJ, Lee IM, Leonard H, Li CM, Lowenheim H, Magnusson PKE, van Meurs J, Milani L, Morton CC, Mäkitie A, Nalls MA, Nardone GG, Nygaard M, Palviainen T, Pratt S, Quaranta N, Rämö J, Saarentaus E, Sardone R, Satizabal CL, Schweinfurth JM, Seshadri S, Shiroma E, Shulman E, Simonsick E, Spankovich C, Tropitzsch A, Lauschke VM, Sullivan PF, Goedegebure A, Cederroth CR, Williams FMK, and Nagtegaal AP
- Subjects
- Animals, Cochlea, Genome-Wide Association Study, Humans, Mice, Stria Vascularis, Deafness, Hearing Loss genetics
- Abstract
Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss., Competing Interests: Declaration of interests The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. C.R.C. is supported by the UK National Institute for Health Research (NIHR) Biomedical Research Center but the views expressed herein are his own and do not represent those of NIHR nor the UK Department of Health and Social Care. Y.Z. and V.M.L. are co-founders and shareholders of PersoMedix AB. In addition, V.M.L. is CEO and shareholder of HepaPredict AB and discloses support by the Robert Bosch Foundation, Merck KGaA, and Eli Lilly and Company. J.H.L. is co-founder and share-holder of Oscellaria AB. H.L. receives support from a consulting contract between Data Tecnica International and the National Institute on Aging (NIA), National Institutes of Health (NIH). M.A.N. received a competitive contract awarded to Data Tecnica International LLC by the National Institutes of Health to support open science research, and he also currently serves on the scientific advisory board for Clover Therapeutics and is an advisor to Neuron23 Inc as a data science fellow. P.F.S. is consultant and shareholder of Neumora., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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44. The Association Between Puberty Timing and Body Mass Index in a Longitudinal Setting: The Contribution of Genetic Factors.
- Author
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Silventoinen K, Jelenkovic A, Palviainen T, Dunkel L, and Kaprio J
- Subjects
- Adult, Body Mass Index, Female, Humans, Male, Risk Factors, Waist Circumference genetics, Obesity genetics, Puberty genetics
- Abstract
We analyzed the contribution of genetic factors on the association between puberty timing and body mass index (BMI) using longitudinal data and two approaches: (i) genetic twin design and (ii) polygenic scores (PGS) of obesity indices. Our data were derived from Finnish cohorts: 9080 twins had information on puberty timing and BMI and 2468 twins also had genetic data. Early puberty timing was moderately associated with higher BMI in childhood in both boys and girls; in adulthood these correlations were weaker and largely disappeared after adjusting for childhood BMI. The largest proportion of these correlations was attributable to genetic factors. The higher PGSs of BMI and waist circumference were associated with earlier timing of puberty in girls, whereas weaker associations were found in boys. Early puberty is not an independent risk factor for adult obesity but rather reflects the association between puberty timing and childhood BMI contributed by genetic predisposition., (© 2022. The Author(s).)
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- 2022
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45. Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.
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Howe LJ, Nivard MG, Morris TT, Hansen AF, Rasheed H, Cho Y, Chittoor G, Ahlskog R, Lind PA, Palviainen T, van der Zee MD, Cheesman R, Mangino M, Wang Y, Li S, Klaric L, Ratliff SM, Bielak LF, Nygaard M, Giannelis A, Willoughby EA, Reynolds CA, Balbona JV, Andreassen OA, Ask H, Baras A, Bauer CR, Boomsma DI, Campbell A, Campbell H, Chen Z, Christofidou P, Corfield E, Dahm CC, Dokuru DR, Evans LM, de Geus EJC, Giddaluru S, Gordon SD, Harden KP, Hill WD, Hughes A, Kerr SM, Kim Y, Kweon H, Latvala A, Lawlor DA, Li L, Lin K, Magnus P, Magnusson PKE, Mallard TT, Martikainen P, Mills MC, Njølstad PR, Overton JD, Pedersen NL, Porteous DJ, Reid J, Silventoinen K, Southey MC, Stoltenberg C, Tucker-Drob EM, Wright MJ, Hewitt JK, Keller MC, Stallings MC, Lee JJ, Christensen K, Kardia SLR, Peyser PA, Smith JA, Wilson JF, Hopper JL, Hägg S, Spector TD, Pingault JB, Plomin R, Havdahl A, Bartels M, Martin NG, Oskarsson S, Justice AE, Millwood IY, Hveem K, Naess Ø, Willer CJ, Åsvold BO, Koellinger PD, Kaprio J, Medland SE, Walters RG, Benjamin DJ, Turley P, Evans DM, Davey Smith G, Hayward C, Brumpton B, Hemani G, and Davies NM
- Subjects
- Humans, Mendelian Randomization Analysis, Multifactorial Inheritance genetics, Phenotype, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics
- Abstract
Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects., (© 2022. The Author(s).)
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- 2022
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46. Polygenic Score for Physical Activity Is Associated with Multiple Common Diseases.
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Sillanpää E, Palviainen T, Ripatti S, Kujala UM, and Kaprio J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cardiometabolic Risk Factors, Cardiovascular Diseases etiology, Cardiovascular Diseases mortality, Case-Control Studies, Child, Child, Preschool, Female, Finland epidemiology, Genetic Markers, Genome-Wide Association Study, Genotype, Humans, Infant, Linear Models, Logistic Models, Male, Metabolic Diseases etiology, Metabolic Diseases mortality, Middle Aged, Risk Assessment, Young Adult, Cardiovascular Diseases genetics, Cardiovascular Diseases prevention & control, Clinical Decision Rules, Exercise genetics, Genetic Pleiotropy, Metabolic Diseases genetics, Metabolic Diseases prevention & control
- Abstract
Introduction: Genetic pleiotropy, in which the same genes affect two or more traits, may partially explain the frequently observed associations between high physical activity (PA) and later reduced morbidity or mortality. This study investigated associations between PA polygenic risk scores (PRS) and cardiometabolic diseases among the Finnish population., Methods: PRS for device-measured overall PA were adapted to a FinnGen study cohort of 218,792 individuals with genomewide genotyping and extensive digital longitudinal health register data. Associations between PA PRS and body mass index, diseases, and mortality were analyzed with linear and logistic regression models., Results: A high PA PRS predicted a lower body mass index (β = -0.025 kg·m-2 per one SD change in PA PRS, SE = 0.013, P = 1.87 × 10-80). The PA PRS also predicted a lower risk for diseases that typically develop later in life or not at all among highly active individuals. A lower disease risk was systematically observed for cardiovascular diseases (odds ratio [OR] per 1 SD change in PA PRS = 0.95, P = 9.5 × 10-19) and, for example, hypertension [OR = 0.93, P = 2.7 × 10-44), type 2 diabetes (OR = 0.91, P = 4.1 × 10-42), and coronary heart disease (OR = 0.95, P = 1.2 × 10-9). Participants with high PA PRS had also lower mortality risk (OR = 0.97, P = 0.0003)., Conclusions: Genetically less active persons are at a higher risk of developing cardiometabolic diseases, which may partly explain the previously observed associations between low PA and higher disease and mortality risk. The same inherited physical fitness and metabolism-related mechanisms may be associated both with PA levels and with cardiometabolic disease risk., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)
- Published
- 2022
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47. The genetic background of the associations between sense of coherence and mental health, self-esteem and personality.
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Silventoinen K, Vuoksimaa E, Volanen SM, Palviainen T, Rose RJ, Suominen S, and Kaprio J
- Subjects
- Female, Genetic Background, Humans, Male, Mental Health, Personality genetics, Personality Inventory, Depressive Disorder, Major, Sense of Coherence
- Abstract
Purpose: Sense of coherence (SOC) represents coping and can be considered an essential component of mental health. SOC correlates with mental health and personality, but the background of these associations is poorly understood. We analyzed the role of genetic factors behind the associations of SOC with mental health, self-esteem and personality using genetic twin modeling and polygenic scores (PGS)., Methods: Information on SOC (13-item Orientation of Life Questionnaire), four mental health indicators, self-esteem and personality (NEO Five Factor Inventory Questionnaire) was collected from 1295 Finnish twins at 20-27 years of age., Results: In men and women, SOC correlated negatively with depression, alexithymia, schizotypal personality and overall mental health problems and positively with self-esteem. For personality factors, neuroticism was associated with weaker SOC and extraversion, agreeableness and conscientiousness with stronger SOC. All these psychological traits were influenced by genetic factors with heritability estimates ranging from 19 to 66%. Genetic and environmental factors explained these associations, but the genetic correlations were generally stronger. The PGS of major depressive disorder was associated with weaker, and the PGS of general risk tolerance with stronger SOC in men, whereas in women the PGS of subjective well-being was associated with stronger SOC and the PGSs of depression and neuroticism with weaker SOC., Conclusion: Our results indicate that a substantial proportion of genetic variation in SOC is shared with mental health, self-esteem and personality indicators. This suggests that the correlations between these traits reflect a common neurobiological background rather than merely the influence of external stressors., (© 2021. The Author(s).)
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- 2022
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48. Genetic Profile of Endotoxemia Reveals an Association With Thromboembolism and Stroke.
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Leskelä J, Toppila I, Härma MA, Palviainen T, Salminen A, Sandholm N, Pietiäinen M, Kopra E, Pais de Barros JP, Lassenius MI, Kumar A, Harjutsalo V, Roslund K, Forsblom C, Loukola A, Havulinna AS, Lagrost L, Salomaa V, Groop PH, Perola M, Kaprio J, Lehto M, and Pussinen PJ
- Subjects
- Genetic Profile, Genome-Wide Association Study, Humans, Lipopolysaccharides, Lipoproteins, Thrombosis, Endotoxemia genetics, Stroke, Venous Thromboembolism
- Abstract
Background Translocation of lipopolysaccharide from gram-negative bacteria into the systemic circulation results in endotoxemia. In addition to acute infections, endotoxemia is detected in cardiometabolic disorders, such as cardiovascular diseases and obesity. Methods and Results We performed a genome-wide association study of serum lipopolysaccharide activity in 11 296 individuals from 6 different Finnish study cohorts. Endotoxemia was measured by limulus amebocyte lysate assay in the whole population and by 2 other techniques (Endolisa and high-performance liquid chromatography/tandem mass spectrometry) in subpopulations. The associations of the composed genetic risk score of endotoxemia and thrombosis-related clinical end points for 195 170 participants were analyzed in FinnGen. Lipopolysaccharide activity had a genome-wide significant association with 741 single-nucleotide polymorphisms in 5 independent loci, which were mainly located at genes affecting the contact activation of the coagulation cascade and lipoprotein metabolism and explained 1.5% to 9.2% of the variability in lipopolysaccharide activity levels. The closest genes included KNG1 , KLKB1 , F12 , SLC34A1 , YPEL4 , CLP1 , ZDHHC5 , SERPING1 , CBX5 , and LIPC . The genetic risk score of endotoxemia was associated with deep vein thrombosis, pulmonary embolism, pulmonary heart disease, and venous thromboembolism. Conclusions The biological activity of lipopolysaccharide in the circulation (ie, endotoxemia) has a small but highly significant genetic component. Endotoxemia is associated with genetic variation in the contact activation pathway, vasoactivity, and lipoprotein metabolism, which play important roles in host defense, lipopolysaccharide neutralization, and thrombosis, and thereby thromboembolism and stroke.
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- 2021
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49. Genetic meta-analysis of twin birth weight shows high genetic correlation with singleton birth weight.
- Author
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Beck JJ, Pool R, van de Weijer M, Chen X, Krapohl E, Gordon SD, Nygaard M, Debrabant B, Palviainen T, van der Zee MD, Baselmans B, Finnicum CT, Yi L, Lundström S, van Beijsterveldt T, Christiansen L, Heikkilä K, Kittelsrud J, Loukola A, Ollikainen M, Christensen K, Martin NG, Plomin R, Nivard M, Bartels M, Dolan C, Willemsen G, de Geus E, Almqvist C, Magnusson PKE, Mbarek H, Ehli EA, Boomsma DI, and Hottenga JJ
- Subjects
- Adult, Birth Weight genetics, Fetal Development, Gestational Age, Humans, Infant, Newborn, Twins genetics, Genome-Wide Association Study, Pregnancy, Twin
- Abstract
Birth weight (BW) is an important predictor of newborn survival and health and has associations with many adult health outcomes, including cardiometabolic disorders, autoimmune diseases and mental health. On average, twins have a lower BW than singletons as a result of a different pattern of fetal growth and shorter gestational duration. Therefore, investigations into the genetics of BW often exclude data from twins, leading to a reduction in sample size and remaining ambiguities concerning the genetic contribution to BW in twins. In this study, we carried out a genome-wide association meta-analysis of BW in 42 212 twin individuals and found a positive correlation of beta values (Pearson's r = 0.66, 95% confidence interval [CI]: 0.47-0.77) with 150 previously reported genome-wide significant variants for singleton BW. We identified strong positive genetic correlations between BW in twins and numerous anthropometric traits, most notably with BW in singletons (genetic correlation [rg] = 0.92, 95% CI: 0.66-1.18). Genetic correlations of BW in twins with a series of health-related traits closely resembled those previously observed for BW in singletons. Polygenic scores constructed from a genome-wide association study on BW in the UK Biobank demonstrated strong predictive power in a target sample of Dutch twins and singletons. Together, our results indicate that a similar genetic architecture underlies BW in twins and singletons and that future genome-wide studies might benefit from including data from large twin registers., (© The Author(s) 2021. Published by Oxford University Press.)
- Published
- 2021
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50. Genetic association study of childhood aggression across raters, instruments, and age.
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Ip HF, van der Laan CM, Krapohl EML, Brikell I, Sánchez-Mora C, Nolte IM, St Pourcain B, Bolhuis K, Palviainen T, Zafarmand H, Colodro-Conde L, Gordon S, Zayats T, Aliev F, Jiang C, Wang CA, Saunders G, Karhunen V, Hammerschlag AR, Adkins DE, Border R, Peterson RE, Prinz JA, Thiering E, Seppälä I, Vilor-Tejedor N, Ahluwalia TS, Day FR, Hottenga JJ, Allegrini AG, Rimfeld K, Chen Q, Lu Y, Martin J, Soler Artigas M, Rovira P, Bosch R, Español G, Ramos Quiroga JA, Neumann A, Ensink J, Grasby K, Morosoli JJ, Tong X, Marrington S, Middeldorp C, Scott JG, Vinkhuyzen A, Shabalin AA, Corley R, Evans LM, Sugden K, Alemany S, Sass L, Vinding R, Ruth K, Tyrrell J, Davies GE, Ehli EA, Hagenbeek FA, De Zeeuw E, Van Beijsterveldt TCEM, Larsson H, Snieder H, Verhulst FC, Amin N, Whipp AM, Korhonen T, Vuoksimaa E, Rose RJ, Uitterlinden AG, Heath AC, Madden P, Haavik J, Harris JR, Helgeland Ø, Johansson S, Knudsen GPS, Njolstad PR, Lu Q, Rodriguez A, Henders AK, Mamun A, Najman JM, Brown S, Hopfer C, Krauter K, Reynolds C, Smolen A, Stallings M, Wadsworth S, Wall TL, Silberg JL, Miller A, Keltikangas-Järvinen L, Hakulinen C, Pulkki-Råback L, Havdahl A, Magnus P, Raitakari OT, Perry JRB, Llop S, Lopez-Espinosa MJ, Bønnelykke K, Bisgaard H, Sunyer J, Lehtimäki T, Arseneault L, Standl M, Heinrich J, Boden J, Pearson J, Horwood LJ, Kennedy M, Poulton R, Eaves LJ, Maes HH, Hewitt J, Copeland WE, Costello EJ, Williams GM, Wray N, Järvelin MR, McGue M, Iacono W, Caspi A, Moffitt TE, Whitehouse A, Pennell CE, Klump KL, Burt SA, Dick DM, Reichborn-Kjennerud T, Martin NG, Medland SE, Vrijkotte T, Kaprio J, Tiemeier H, Davey Smith G, Hartman CA, Oldehinkel AJ, Casas M, Ribasés M, Lichtenstein P, Lundström S, Plomin R, Bartels M, Nivard MG, and Boomsma DI
- Subjects
- Adolescent, Child, Child, Preschool, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Infant, Retrospective Studies, Aggression, Mental Disorders
- Abstract
Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG
overall ) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall . The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg ) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rg s with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG., (© 2021. The Author(s).)- Published
- 2021
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