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3. Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.

Author

Young, K. S., Purves, K. L., Hübel, C., Davies, M. R., Thompson, K. N., Bristow, S., Krebs, G., Danese, A., Hirsch, C., Parsons, C. E., Vassos, E., Adey, B. N., Bright, S., Hegemann, L., Lee, Y. T., Kalsi, G., Monssen, D., Mundy, J., Peel, A. J., and Rayner, C.

Subjects
POST-traumatic stress disorder, RETROSPECTIVE studies, PSYCHOLOGICAL tests, MENTAL depression, RESEARCH funding, QUESTIONNAIRES, ANXIETY, COVID-19 pandemic, LONGITUDINAL method
Abstract

Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors. Method: Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change. Results: Prospective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status. Conclusions: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity. [ABSTRACT FROM AUTHOR]

Published
2023
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4. Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK

Author

Young, K. S., primary, Purves, K. L., additional, Hübel, C., additional, Davies, M. R., additional, Thompson, K. N., additional, Bristow, S., additional, Krebs, G., additional, Danese, A., additional, Hirsch, C., additional, Parsons, C. E., additional, Vassos, E., additional, Adey, B. N., additional, Bright, S., additional, Hegemann, L., additional, Lee, Y. T., additional, Kalsi, G., additional, Monssen, D., additional, Mundy, J., additional, Peel, A. J., additional, Rayner, C., additional, Rogers, H. C., additional, ter Kuile, A., additional, Ward, C., additional, York, K., additional, Lin, Y., additional, Palmos, A. B., additional, Schmidt, U., additional, Veale, D., additional, Nicholson, T. R., additional, Pollak, T. A., additional, Stevelink, S. A. M., additional, Moukhtarian, T., additional, Martineau, A. R., additional, Holt, H., additional, Maughan, B., additional, Al-Chalabi, A., additional, Chaudhuri, K. Ray, additional, Richardson, M. P., additional, Bradley, J. R., additional, Chinnery, P. F., additional, Kingston, N., additional, Papadia, S., additional, Stirrups, K. E., additional, Linger, R., additional, Hotopf, M., additional, Eley, T. C., additional, and Breen, G., additional

Published
2022
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5. Common Genetic Variation and Age of Onset of Anorexia Nervosa

Author

Watson, H.J. Thornton, L.M. Yilmaz, Z. Baker, J.H. Coleman, J.R.I. Adan, R.A.H. Alfredsson, L. Andreassen, O.A. Ask, H. Berrettini, W.H. Boehnke, M. Boehm, I. Boni, C. Buehren, K. Bulant, J. Burghardt, R. Chang, X. Cichon, S. Cone, R.D. Courtet, P. Crow, S. Crowley, J.J. Danner, U.N. de Zwaan, M. Dedoussis, G. DeSocio, J.E. Dick, D.M. Dikeos, D. Dina, C. Djurovic, S. Dmitrzak-Weglarz, M. Docampo-Martinez, E. Duriez, P. Egberts, K. Ehrlich, S. Eriksson, J.G. Escaramís, G. Esko, T. Estivill, X. Farmer, A. Fernández-Aranda, F. Fichter, M.M. Föcker, M. Foretova, L. Forstner, A.J. Frei, O. Gallinger, S. Giegling, I. Giuranna, J. Gonidakis, F. Gorwood, P. Gratacòs, M. Guillaume, S. Guo, Y. Hakonarson, H. Hauser, J. Havdahl, A. Hebebrand, J. Helder, S.G. Herms, S. Herpertz-Dahlmann, B. Herzog, W. Hinney, A. Hübel, C. Hudson, J.I. Imgart, H. Jamain, S. Janout, V. Jiménez-Murcia, S. Jones, I.R. Julià, A. Kalsi, G. Kaminská, D. Kaprio, J. Karhunen, L. Kas, M.J.H. Keel, P.K. Kennedy, J.L. Keski-Rahkonen, A. Kiezebrink, K. Klareskog, L. Klump, K.L. Knudsen, G.P.S. La Via, M.C. Le Hellard, S. Leboyer, M. Li, D. Lilenfeld, L. Lin, B. Lissowska, J. Luykx, J. Magistretti, P. Maj, M. Marsal, S. Marshall, C.R. Mattingsdal, M. Meulenbelt, I. Micali, N. Mitchell, K.S. Monteleone, A.M. Monteleone, P. Myers, R. Navratilova, M. Ntalla, I. O'Toole, J.K. Ophoff, R.A. Padyukov, L. Pantel, J. Papežová, H. Pinto, D. Raevuori, A. Ramoz, N. Reichborn-Kjennerud, T. Ricca, V. Ripatti, S. Ripke, S. Ritschel, F. Roberts, M. Rotondo, A. Rujescu, D. Rybakowski, F. Scherag, A. Scherer, S.W. Schmidt, U. Scott, L.J. Seitz, J. Silén, Y. Šlachtová, L. Slagboom, P.E. Slof-Op ‘t Landt, M.C.T. Slopien, A. Sorbi, S. Świątkowska, B. Tortorella, A. Tozzi, F. Treasure, J. Tsitsika, A. Tyszkiewicz-Nwafor, M. Tziouvas, K. van Elburg, A.A. van Furth, E.F. Walton, E. Widen, 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. Mitc and Watson, H.J. Thornton, L.M. Yilmaz, Z. Baker, J.H. Coleman, J.R.I. Adan, R.A.H. Alfredsson, L. Andreassen, O.A. Ask, H. Berrettini, W.H. Boehnke, M. Boehm, I. Boni, C. Buehren, K. Bulant, J. Burghardt, R. Chang, X. Cichon, S. Cone, R.D. Courtet, P. Crow, S. Crowley, J.J. Danner, U.N. de Zwaan, M. Dedoussis, G. DeSocio, J.E. Dick, D.M. Dikeos, D. Dina, C. Djurovic, S. Dmitrzak-Weglarz, M. Docampo-Martinez, E. Duriez, P. Egberts, K. Ehrlich, S. Eriksson, J.G. Escaramís, G. Esko, T. Estivill, X. Farmer, A. Fernández-Aranda, F. Fichter, M.M. Föcker, M. Foretova, L. Forstner, A.J. Frei, O. Gallinger, S. Giegling, I. Giuranna, J. Gonidakis, F. Gorwood, P. Gratacòs, M. Guillaume, S. Guo, Y. Hakonarson, H. Hauser, J. Havdahl, A. Hebebrand, J. Helder, S.G. Herms, S. Herpertz-Dahlmann, B. Herzog, W. Hinney, A. Hübel, C. Hudson, J.I. Imgart, H. Jamain, S. Janout, V. Jiménez-Murcia, S. Jones, I.R. Julià, A. Kalsi, G. Kaminská, D. Kaprio, J. Karhunen, L. Kas, M.J.H. Keel, P.K. Kennedy, J.L. Keski-Rahkonen, A. Kiezebrink, K. Klareskog, L. Klump, K.L. Knudsen, G.P.S. La Via, M.C. Le Hellard, S. Leboyer, M. Li, D. Lilenfeld, L. Lin, B. Lissowska, J. Luykx, J. Magistretti, P. Maj, M. Marsal, S. Marshall, C.R. Mattingsdal, M. Meulenbelt, I. Micali, N. Mitchell, K.S. Monteleone, A.M. Monteleone, P. Myers, R. Navratilova, M. Ntalla, I. O'Toole, J.K. Ophoff, R.A. Padyukov, L. Pantel, J. Papežová, H. Pinto, D. Raevuori, A. Ramoz, N. Reichborn-Kjennerud, T. Ricca, V. Ripatti, S. Ripke, S. Ritschel, F. Roberts, M. Rotondo, A. Rujescu, D. Rybakowski, F. Scherag, A. Scherer, S.W. Schmidt, U. Scott, L.J. Seitz, J. Silén, Y. Šlachtová, L. Slagboom, P.E. Slof-Op ‘t Landt, M.C.T. Slopien, A. Sorbi, S. Świątkowska, B. Tortorella, A. Tozzi, F. Treasure, J. Tsitsika, A. Tyszkiewicz-Nwafor, M. Tziouvas, K. van Elburg, A.A. van Furth, E.F. Walton, E. Widen, 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. Mitc

Abstract

Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche. Methods: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (<13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism–h2) were 0.01–0.04 for age of onset, 0.16–0.25 for early-onset AN, and 0.17–0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction. © 2021 The Authors

Published
2022

6. A genome-wide association study of anorexia nervosa

Author

Boraska, V, Franklin, C S, Floyd, J A B, Thornton, L M, Huckins, L M, Southam, L, Rayner, N W, Tachmazidou, I, Klump, K L, Treasure, J, Lewis, C M, Schmidt, U, Tozzi, F, Kiezebrink, K, Hebebrand, J, Gorwood, P, Adan, R A H, Kas, M J H, Favaro, A, Santonastaso, P, Fernández-Aranda, F, Gratacos, M, Rybakowski, F, Dmitrzak-Weglarz, M, Kaprio, J, Keski-Rahkonen, A, Raevuori, A, Van Furth, E F, Slof-Op 't Landt, M C T, Hudson, J I, Reichborn-Kjennerud, T, Knudsen, G P S, Monteleone, P, Kaplan, A S, Karwautz, A, Hakonarson, H, Berrettini, W H, Guo, Y, Li, D, Schork, N J, Komaki, G, Ando, T, Inoko, H, Esko, T, Fischer, K, Männik, K, Metspalu, A, Baker, J H, Cone, R D, Dackor, J, DeSocio, J E, Hilliard, C E, O'Toole, J K, Pantel, J, Szatkiewicz, J P, Taico, C, Zerwas, S, Trace, S E, Davis, O S P, Helder, S, Bühren, K, Burghardt, R, de Zwaan, M, Egberts, K, Ehrlich, S, Herpertz-Dahlmann, B, Herzog, W, Imgart, H, Scherag, A, Scherag, S, Zipfel, S, Boni, C, Ramoz, N, Versini, A, Brandys, M K, Danner, U N, de Kovel, C, Hendriks, J, Koeleman, B P C, Ophoff, R A, Strengman, E, van Elburg, A A, Bruson, A, Clementi, M, Degortes, D, Forzan, M, Tenconi, E, Docampo, E, Escaramís, G, Jiménez-Murcia, S, Lissowska, J, Rajewski, A, Szeszenia-Dabrowska, N, Slopien, A, Hauser, J, Karhunen, L, Meulenbelt, I, Slagboom, P E, Tortorella, A, Maj, M, Dedoussis, G, Dikeos, D, Gonidakis, F, Tziouvas, K, Tsitsika, A, Papezova, H, Slachtova, L, Martaskova, D, Kennedy, J L, Levitan, R D, Yilmaz, Z, Huemer, J, Koubek, D, Merl, E, Wagner, G, Lichtenstein, P, Breen, G, Cohen-Woods, S, Farmer, A, McGuffin, P, Cichon, S, Giegling, I, Herms, S, Rujescu, D, Schreiber, S, Wichmann, H-E, Dina, C, Sladek, R, Gambaro, G, Soranzo, N, Julia, A, Marsal, S, Rabionet, R, Gaborieau, V, Dick, D M, Palotie, A, Ripatti, S, Widén, E, Andreassen, O A, Espeseth, T, Lundervold, A, Reinvang, I, Steen, V M, Le Hellard, S, Mattingsdal, M, Ntalla, I, Bencko, V, Foretova, L, Janout, V, Navratilova, M, Gallinger, S, Pinto, D, Scherer, S W, Aschauer, H, Carlberg, L, Schosser, A, Alfredsson, L, Ding, B, Klareskog, L, Padyukov, L, Courtet, P, Guillaume, S, Jaussent, I, Finan, C, Kalsi, G, Roberts, M, Logan, D W, Peltonen, L, Ritchie, G R S, Barrett, J C, Estivill, X, Hinney, A, Sullivan, P F, Collier, D A, Zeggini, E, and Bulik, C M

Published
2014
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7. Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Author

Huckins, L M, Hatzikotoulas, K, Southam, L, Thornton, L M, Steinberg, J, Aguilera-McKay, F, Treasure, J, Schmidt, U, Gunasinghe, C, Romero, A, Curtis, C, Rhodes, D, Moens, J, Kalsi, G, Dempster, D, Leung, R, Keohane, A, Burghardt, R, Ehrlich, S, Hebebrand, J, Hinney, A, Ludolph, A, Walton, E, Deloukas, P, Hofman, A, Palotie, A, Palta, P, van Rooij, F J A, Stirrups, K, Adan, R, Boni, C, Cone, R, Dedoussis, G, van Furth, E, Gonidakis, F, Gorwood, P, Hudson, J, Kaprio, J, Kas, M, Keski-Rahonen, A, Kiezebrink, K, Knudsen, G-P, Maj, M, Monteleone, A M, Monteleone, P, Raevuori, A H, Reichborn-Kjennerud, T, Tozzi, F, Tsitsika, A, van Elburg, A, Collier, D A, Sullivan, P F, Breen, G, Bulik, C M, and Zeggini, E

Published
2018
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12. Meta-analysis of 32 genome-wide linkage studies of schizophrenia

Author

Ng, M Y M, Levinson, D F, Faraone, S V, Suarez, B K, DeLisi, L E, Arinami, T, Riley, B, Paunio, T, Pulver, A E, Irmansyah, Holmans, P A, Escamilla, M, Wildenauer, D B, Williams, N M, Laurent, C, Mowry, B J, Brzustowicz, L M, Maziade, M, Sklar, P, Garver, D L, Abecasis, G R, Lerer, B, Fallin, M D, Gurling, H M D, Gejman, P V, Lindholm, E, Moises, H W, Byerley, W, Wijsman, E M, Forabosco, P, Tsuang, M T, Hwu, H-G, Okazaki, Y, Kendler, K S, Wormley, B, Fanous, A, Walsh, D, O'Neill, F A, Peltonen, L, Nestadt, G, Lasseter, V K, Liang, K Y, Papadimitriou, G M, Dikeos, D G, Schwab, S G, Owen, M J, O'Donovan, M C, Norton, N, Hare, E, Raventos, H, Nicolini, H, Albus, M, Maier, W, Nimgaonkar, V L, Terenius, L, Mallet, J, Jay, M, Godard, S, Nertney, D, Alexander, M, Crowe, R R, Silverman, J M, Bassett, A S, Roy, M-A, Mérette, C, Pato, C N, Pato, M T, Roos, J Louw, Kohn, Y, Amann-Zalcenstein, D, Kalsi, G, McQuillin, A, Curtis, D, Brynjolfson, J, Sigmundsson, T, Petursson, H, Sanders, A R, Duan, J, Jazin, E, Myles-Worsley, M, Karayiorgou, M, and Lewis, C M

Published
2009
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13. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

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

14. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

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&apos and 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&apos

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 substanc

Published
2021

15. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author

Munn-Chernoff, MA, Johnson, EC, Chou, YL, Coleman, JRI, Thornton, LM, Walters, RK, Yilmaz, Z, Baker, JH, Hübel, C, Gordon, S, Medland, SE, Watson, HJ, Gaspar, HA, Bryois, J, Hinney, A, Leppä, VM, Mattheisen, M, Ripke, S, Yao, S, Giusti-Rodríguez, P, Hanscombe, KB, Adan, RAH, Alfredsson, L, Ando, T, Andreassen, OA, Berrettini, WH, Boehm, I, Boni, C, Boraska Perica, V, Buehren, K, Burghardt, R, Cassina, M, Cichon, S, Clementi, M, Cone, RD, Courtet, P, Crow, S, Crowley, JJ, Danner, UN, Davis, OS, Zwaan, M, Dedoussis, G, Degortes, D, DeSocio, JE, Dick, DM, Dikeos, D, Dina, C, Dmitrzak-Weglarz, M, Docampo, E, Duncan, LE, Egberts, K, Ehrlich, S, Escaramís, G, Esko, T, Estivill, X, Farmer, A, Favaro, A, Fernández-Aranda, F, Fichter, MM, Fischer, K, Föcker, M, Foretova, L, Forstner, AJ, Forzan, M, Franklin, CS, 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, SG, Herms, S, Herpertz-Dahlmann, B, Herzog, W, Huckins, LM, Hudson, JI, Imgart, H, Inoko, H, Janout, V, Jiménez-Murcia, S, Julià, A, Kalsi, G, Kaminská, D, Karhunen, L, Karwautz, A, Kas, MJH, Kennedy, JL, Keski-Rahkonen, A, Kiezebrink, K, Kim, YR, Klump, KL, Knudsen, GP, La Via, MC, Le Hellard, S, Levitan, RD, Li, D, Lilenfeld, L, Lin, BD, Lissowska, J, Luykx, J, Magistretti, PJ, Maj, M, Mannik, K, Marsal, S, Marshall, CR, 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, JK, Ophoff, Roel, 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, SW, Schmidt, U, Schork, NJ, Schosser, A, Seitz, J, Slachtova, L, Slagboom, PE, Slof-Op't Landt, MCT, Slopien, A, Sorbi, S, ?wi?tkowska, B, Szatkiewicz, JP, Tachmazidou, I, Tenconi, E, Tortorella, A, Tozzi, F, Treasure, J, Tsitsika, A, Tyszkiewicz-Nwafor, M, Tziouvas, K, van Elburg, AA, van Furth, EF, Wagner, G, Walton, E, Widen, E, Zeggini, E, Zerwas, S, Zipfel, S, Bergen, AW, Boden, JM, Brandt, H, Crawford, S, Halmi, KA, Horwood, LJ, Johnson, C, Kaplan, AS, Kaye, WH, Mitchell, J E, Olsen, CM, Pearson, JF, Pedersen, NL, Strober, M, Werge, T, Whiteman, DC, Woodside, DB, Grove, J, Henders, AK, Larsen, J T, Parker, R, Petersen, LV, Jordan, J, Kennedy, MA, Birgegård, A, Lichtenstein, P, Norring, C, Landén, M, Mortensen, PB, Polimanti, R, McClintick, JN, Adkins, AE, Aliev, F, Bacanu, SA, Batzler, A, Bertelsen, S, Biernacka, JM, Bigdeli, TB, Chen, L S, Clarke, TK, Degenhardt, F, Docherty, AR, Edwards, AC, Foo, JC, Fox, L, Frank, J, Hack, LM, Hartmann, AM, Hartz, SM, Heilmann-Heimbach, S, Hodgkinson, C, Hoffmann, P, Hottenga, JJ, Konte, B, Lahti, J, Lahti-Pulkkinen, M, Lai, D, Ligthart, L, Loukola, A, Maher, BS, Mbarek, H, McIntosh, AM, McQueen, MB, Meyers, JL, Milaneschi, Y, Palviainen, T, Peterson, RE, Ryu, E, Saccone, N L, Salvatore, JE, Sanchez-Roige, S, Schwandt, M, Sherva, R, Streit, F, Strohmaier, J, Thomas, N, Wang, JCY, Webb, BT, Wedow, R, Wetherill, L, Wills, AG, Zhou, H, Boardman, JD, Chen, D, Choi, D S, Copeland, WE, Culverhouse, RC, Dahmen, N, Degenhardt, L, Domingue, BW, Frye, MA, Gäebel, W, Hayward, C, Ising, M, Keyes, M, Kiefer, F, Koller, G, Kramer, J (John), Kuperman, S, Lucae, S, Lynskey, MT, Maier, W, Mann, K, Männistö, S, Müller-Myhsok, B, Murray, AD, Nurnberger, JI, Preuss, U, Räikkönen, K, Reynolds, MD, Ridinger, M, Scherbaum, N, Schuckit, MA, Soyka, M, Treutlein, J, Witt, SH, Wodarz, N, Zill, P, Adkins, DE, Boomsma, DI, Bierut, LJ, Brown, S, Bucholz, KK, Costello, EJ, Wit, HJ, Diazgranados, N, Eriksson, JG, Farrer, LA, Foroud, TM, Gillespie, NA, Goate, AM, Goldman, D, Grucza, RA, Hancock, DB, Harris, KM, Hesselbrock, V, Hewitt, JK, Hopfer, CJ, Iacono, WG, Johnson, E O, Karpyak, VM, Kendler, KS, Kranzler, HR, Krauter, K, Lind, PA, McGue, M, MacKillop, J, Madden, PA, Maes, HH, Magnusson, PKE, Nelson, EC, Nöthen, MM, Palmer, AA, Penninx, BWJH, Porjesz, B, Rice, JP, Rietschel, M, Riley, BP, Rose, RJ, Shen, PH, Silberg, J, Stallings, MC, Tarter, RE, Vanyukov, MM, Vrieze, S, Wall, TL, Whitfield, JB, Zhao, H, Neale, BM, Wade, TD, Heath, AC, Montgomery, GW, Martin, NG, Sullivan, PF, Kaprio, J, Breen, G, Gelernter, J, Edenberg, HJ, Bulik, CM, Agrawal, A, Munn-Chernoff, MA, Johnson, EC, Chou, YL, Coleman, JRI, Thornton, LM, Walters, RK, Yilmaz, Z, Baker, JH, Hübel, C, Gordon, S, Medland, SE, Watson, HJ, Gaspar, HA, Bryois, J, Hinney, A, Leppä, VM, Mattheisen, M, Ripke, S, Yao, S, Giusti-Rodríguez, P, Hanscombe, KB, Adan, RAH, Alfredsson, L, Ando, T, Andreassen, OA, Berrettini, WH, Boehm, I, Boni, C, Boraska Perica, V, Buehren, K, Burghardt, R, Cassina, M, Cichon, S, Clementi, M, Cone, RD, Courtet, P, Crow, S, Crowley, JJ, Danner, UN, Davis, OS, Zwaan, M, Dedoussis, G, Degortes, D, DeSocio, JE, Dick, DM, Dikeos, D, Dina, C, Dmitrzak-Weglarz, M, Docampo, E, Duncan, LE, Egberts, K, Ehrlich, S, Escaramís, G, Esko, T, Estivill, X, Farmer, A, Favaro, A, Fernández-Aranda, F, Fichter, MM, Fischer, K, Föcker, M, Foretova, L, Forstner, AJ, Forzan, M, Franklin, CS, 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, SG, Herms, S, Herpertz-Dahlmann, B, Herzog, W, Huckins, LM, Hudson, JI, Imgart, H, Inoko, H, Janout, V, Jiménez-Murcia, S, Julià, A, Kalsi, G, Kaminská, D, Karhunen, L, Karwautz, A, Kas, MJH, Kennedy, JL, Keski-Rahkonen, A, Kiezebrink, K, Kim, YR, Klump, KL, Knudsen, GP, La Via, MC, Le Hellard, S, Levitan, RD, Li, D, Lilenfeld, L, Lin, BD, Lissowska, J, Luykx, J, Magistretti, PJ, Maj, M, Mannik, K, Marsal, S, Marshall, CR, 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, JK, Ophoff, Roel, 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, SW, Schmidt, U, Schork, NJ, Schosser, A, Seitz, J, Slachtova, L, Slagboom, PE, Slof-Op't Landt, MCT, Slopien, A, Sorbi, S, ?wi?tkowska, B, Szatkiewicz, JP, Tachmazidou, I, Tenconi, E, Tortorella, A, Tozzi, F, Treasure, J, Tsitsika, A, Tyszkiewicz-Nwafor, M, Tziouvas, K, van Elburg, AA, van Furth, EF, Wagner, G, Walton, E, Widen, E, Zeggini, E, Zerwas, S, Zipfel, S, Bergen, AW, Boden, JM, Brandt, H, Crawford, S, Halmi, KA, Horwood, LJ, Johnson, C, Kaplan, AS, Kaye, WH, Mitchell, J E, Olsen, CM, Pearson, JF, Pedersen, NL, Strober, M, Werge, T, Whiteman, DC, Woodside, DB, Grove, J, Henders, AK, Larsen, J T, Parker, R, Petersen, LV, Jordan, J, Kennedy, MA, Birgegård, A, Lichtenstein, P, Norring, C, Landén, M, Mortensen, PB, Polimanti, R, McClintick, JN, Adkins, AE, Aliev, F, Bacanu, SA, Batzler, A, Bertelsen, S, Biernacka, JM, Bigdeli, TB, Chen, L S, Clarke, TK, Degenhardt, F, Docherty, AR, Edwards, AC, Foo, JC, Fox, L, Frank, J, Hack, LM, Hartmann, AM, Hartz, SM, Heilmann-Heimbach, S, Hodgkinson, C, Hoffmann, P, Hottenga, JJ, Konte, B, Lahti, J, Lahti-Pulkkinen, M, Lai, D, Ligthart, L, Loukola, A, Maher, BS, Mbarek, H, McIntosh, AM, McQueen, MB, Meyers, JL, Milaneschi, Y, Palviainen, T, Peterson, RE, Ryu, E, Saccone, N L, Salvatore, JE, Sanchez-Roige, S, Schwandt, M, Sherva, R, Streit, F, Strohmaier, J, Thomas, N, Wang, JCY, Webb, BT, Wedow, R, Wetherill, L, Wills, AG, Zhou, H, Boardman, JD, Chen, D, Choi, D S, Copeland, WE, Culverhouse, RC, Dahmen, N, Degenhardt, L, Domingue, BW, Frye, MA, Gäebel, W, Hayward, C, Ising, M, Keyes, M, Kiefer, F, Koller, G, Kramer, J (John), Kuperman, S, Lucae, S, Lynskey, MT, Maier, W, Mann, K, Männistö, S, Müller-Myhsok, B, Murray, AD, Nurnberger, JI, Preuss, U, Räikkönen, K, Reynolds, MD, Ridinger, M, Scherbaum, N, Schuckit, MA, Soyka, M, Treutlein, J, Witt, SH, Wodarz, N, Zill, P, Adkins, DE, Boomsma, DI, Bierut, LJ, Brown, S, Bucholz, KK, Costello, EJ, Wit, HJ, Diazgranados, N, Eriksson, JG, Farrer, LA, Foroud, TM, Gillespie, NA, Goate, AM, Goldman, D, Grucza, RA, Hancock, DB, Harris, KM, Hesselbrock, V, Hewitt, JK, Hopfer, CJ, Iacono, WG, Johnson, E O, Karpyak, VM, Kendler, KS, Kranzler, HR, Krauter, K, Lind, PA, McGue, M, MacKillop, J, Madden, PA, Maes, HH, Magnusson, PKE, Nelson, EC, Nöthen, MM, Palmer, AA, Penninx, BWJH, Porjesz, B, Rice, JP, Rietschel, M, Riley, BP, Rose, RJ, Shen, PH, Silberg, J, Stallings, MC, Tarter, RE, Vanyukov, MM, Vrieze, S, Wall, TL, Whitfield, JB, Zhao, H, Neale, BM, Wade, TD, Heath, AC, Montgomery, GW, Martin, NG, Sullivan, PF, Kaprio, J, Breen, G, Gelernter, J, Edenberg, HJ, Bulik, CM, and Agrawal, A

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 phenotyp

Published
2021

18. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease

Author

Bryois J., Skene N. G., Hansen T. F., Kogelman L. J. A., Watson H. J., Liu Z., Adan R., Alfredsson L., Ando T., Andreassen O., Baker J., Bergen A., Berrettini W., Birgegard A., Boden J., Boehm I., Boni C., Boraska Perica V., Brandt H., Breen G., Buehren K., Bulik C., Burghardt R., Cassina M., Cichon S., Clementi M., Coleman J., Cone R., Courtet P., Crawford S., Crow S., Crowley J., Danner U., Davis O., de Zwaan M., Dedoussis G., Degortes D., DeSocio J., Dick D., Dikeos D., Dina C., Dmitrzak-Weglarz M., Docampo Martinez E., Duncan L., Egberts K., Ehrlich S., Escaramis G., Esko T., Estivill X., Farmer A., Favaro A., Fernandez-Aranda F., Fichter M., Fischer K., Focker M., Foretova L., Forstner A., Forzan M., Franklin C., Gallinger S., Gaspar H., Giegling I., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Gorwood P., Gratacos Mayora M., Grove J., Guillaume S., Guo Y., Hakonarson H., Halmi K., Hanscombe K., Hatzikotoulas K., Hauser J., Hebebrand J., Helder S., Henders A., Herms S., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L. J., Hubel C., Huckins L., Hudson J., Imgart H., Inoko H., Janout V., Jimenez-Murcia S., Johnson C., Jordan J., Julia A., Jureus A., Kalsi G., Kaminska D., Kaplan A., Kaprio J., Karhunen L., Karwautz A., Kas M., Kaye W., Kennedy J., Kennedy M., Keski-Rahkonen A., Kiezebrink K., Kim Y. -R., Kirk K., Klareskog L., Klump K., Knudsen G. P., La Via M., Landen M., Larsen J., Le Hellard S., Leppa V., Levitan R., Li D., Lichtenstein P., Lilenfeld L., Lin B. D., Lissowska J., Luykx J., Magistretti P., Maj M., Mannik K., Marsal S., Marshall C., Martin N., Mattheisen M., Mattingsdal M., McDevitt S., McGuffin P., Medland S., Metspalu A., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A. M., Montgomery G., Mortensen P. B., Munn-Chernoff M., Nacmias B., Navratilova M., Norring C., Ntalla I., Olsen C., Ophoff R., O'Toole J., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J., Pedersen N., Petersen L., Pinto D., Purves K., Rabionet R., Raevuori A., Ramoz N., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ripke S., Ritschel F., Roberts M., Rotondo A., Rujescu D., Rybakowski F., Santonastaso P., Scherag A., Scherer S., Schmidt U., Schork N., Schosser A., Seitz J., Slachtova L., Slagboom P. E., Slof-Op 't Landt M., Slopien A., Sorbi S., Strober M., Stuber G., Sullivan P., Swiatkowska B., Szatkiewicz J., Tachmazidou I., Tenconi E., Thornton L., Tortorella A., Tozzi F., Treasure J., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A., van Furth E., Wade T., Wagner G., Walton E., Watson H., Werge T., Whiteman D., Widen E., Woodside D. B., Yao S., Yilmaz Z., Zeggini E., Zerwas S., Zipfel S., Anttila V., Artto V., Belin A. C., de Boer I., Boomsma D. I., Borte S., Chasman D. I., Cherkas L., Christensen A. F., Cormand B., Cuenca-Leon E., Davey-Smith G., Dichgans M., van Duijn C., Esserlind A. L., Ferrari M., Frants R. R., Freilinger T., Furlotte N., Gormley P., Griffiths L., Hamalainen E., Hiekkala M., Ikram M. A., Ingason A., Jarvelin M. -R., Kajanne R., Kallela M., Kaunisto M., Kubisch C., Kurki M., Kurth T., Launer L., Lehtimaki T., Lessel D., Ligthart L., Litterman N., Maagdenberg A., Macaya A., Malik R., Mangino M., McMahon G., Muller-Myhsok B., Neale B. M., Northover C., Nyholt D. R., Olesen J., Palta P., Pedersen L., Posthuma D., Pozo-Rosich P., Pressman A., Raitakari O., Schurks M., Sintas C., Stefansson K., Stefansson H., Steinberg S., Strachan D., Terwindt G., Vila-Pueyo M., Wessman M., Winsvold B. S., Zhao H., Zwart J. A., Agee M., Alipanahi B., Auton A., Bell R., Bryc K., Elson S., Fontanillas P., Heilbron K., Hinds D., Huber K., Kleinman A., McCreight J., McIntyre M., Mountain J., Noblin E., Pitts S., Sathirapongsasuti J., Sazonova O., Shelton J., Shringarpure S., Tian C., Tung J., Vacic V., Wilson C., Brueggeman L., Bulik C. M., Arenas E., Hjerling-Leffler J., Sullivan P. F., Functional Genomics, APH - Methodology, APH - Mental Health, Biological Psychology, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Bryois, Julien, Hansen, Thomas Folkmann, Kogelman, Lisette J A, Watson, Hunna J, Breen, Gerome, Bulik, Cynthia M, Micali, Nadia, van Duijn, C, Kas lab, Bryois, J., Skene, N. G., Hansen, T. F., Kogelman, L. J. A., Watson, H. J., Liu, Z., Adan, R., Alfredsson, L., Ando, T., Andreassen, O., Baker, J., Bergen, A., Berrettini, W., Birgegard, A., Boden, J., Boehm, I., Boni, C., Boraska Perica, V., Brandt, H., Breen, G., Buehren, K., Bulik, C., Burghardt, R., Cassina, M., Cichon, S., Clementi, M., Coleman, J., Cone, R., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U., Davis, O., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J., Dick, D., Dikeos, D., Dina, C., Dmitrzak-Weglarz, M., Docampo Martinez, E., Duncan, L., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Farmer, A., Favaro, A., Fernandez-Aranda, F., Fichter, M., Fischer, K., Focker, M., Foretova, L., Forstner, A., Forzan, M., Franklin, C., Gallinger, S., Gaspar, H., Giegling, I., Giuranna, J., Giusti-Rodriquez, P., Gonidakis, F., Gordon, S., Gorwood, P., Gratacos Mayora, M., Grove, J., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K., Hanscombe, K., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S., Henders, A., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Horwood, L. J., Hubel, C., Huckins, L., Hudson, J., Imgart, H., Inoko, H., Janout, V., Jimenez-Murcia, S., Johnson, C., Jordan, J., Julia, A., Jureus, A., Kalsi, G., Kaminska, D., Kaplan, A., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M., Kaye, W., Kennedy, J., Kennedy, M., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Kirk, K., Klareskog, L., Klump, K., Knudsen, G. P., La Via, M., Landen, M., Larsen, J., Le Hellard, S., Leppa, V., Levitan, R., Li, D., Lichtenstein, P., Lilenfeld, L., Lin, B. D., Lissowska, J., Luykx, J., Magistretti, P., Maj, M., Mannik, K., Marsal, S., Marshall, C., Martin, N., Mattheisen, M., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Medland, S., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Montgomery, G., Mortensen, P. B., Munn-Chernoff, M., Nacmias, B., Navratilova, M., Norring, C., Ntalla, I., Olsen, C., Ophoff, R., O'Toole, J., Padyukov, L., Palotie, A., Pantel, J., Papezova, H., Parker, R., Pearson, J., Pedersen, N., Petersen, L., Pinto, D., Purves, K., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ripke, S., Ritschel, F., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S., Schmidt, U., Schork, N., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op 't Landt, M., Slopien, A., Sorbi, S., Strober, M., Stuber, G., Sullivan, P., Swiatkowska, B., Szatkiewicz, J., Tachmazidou, I., Tenconi, E., Thornton, L., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A., van Furth, E., Wade, T., Wagner, G., Walton, E., Watson, H., Werge, T., Whiteman, D., Widen, E., Woodside, D. B., Yao, S., Yilmaz, Z., Zeggini, E., Zerwas, S., Zipfel, S., Anttila, V., Artto, V., Belin, A. C., de Boer, I., Boomsma, D. I., Borte, S., Chasman, D. I., Cherkas, L., Christensen, A. F., Cormand, B., Cuenca-Leon, E., Davey-Smith, G., Dichgans, M., van Duijn, C., Esserlind, A. L., Ferrari, M., Frants, R. R., Freilinger, T., Furlotte, N., Gormley, P., Griffiths, L., Hamalainen, E., Hiekkala, M., Ikram, M. A., Ingason, A., Jarvelin, M. -R., Kajanne, R., Kallela, M., Kaunisto, M., Kubisch, C., Kurki, M., Kurth, T., Launer, L., Lehtimaki, T., Lessel, D., Ligthart, L., Litterman, N., Maagdenberg, A., Macaya, A., Malik, R., Mangino, M., Mcmahon, G., Muller-Myhsok, B., Neale, B. M., Northover, C., Nyholt, D. R., Olesen, J., Palta, P., Pedersen, L., Posthuma, D., Pozo-Rosich, P., Pressman, A., Raitakari, O., Schurks, M., Sintas, C., Stefansson, K., Stefansson, H., Steinberg, S., Strachan, D., Terwindt, G., Vila-Pueyo, M., Wessman, M., Winsvold, B. S., Zhao, H., Zwart, J. A., Agee, M., Alipanahi, B., Auton, A., Bell, R., Bryc, K., Elson, S., Fontanillas, P., Heilbron, K., Hinds, D., Huber, K., Kleinman, A., Mccreight, J., Mcintyre, M., Mountain, J., Noblin, E., Pitts, S., Sathirapongsasuti, J., Sazonova, O., Shelton, J., Shringarpure, S., Tian, C., Tung, J., Vacic, V., Wilson, C., Brueggeman, L., Bulik, C. M., Arenas, E., Hjerling-Leffler, J., and Sullivan, P. F.

Subjects
Nervous system, Netherlands Twin Register (NTR), Aging, Parkinson's disease, Medizin, Genome-wide association study, Disease, Neurodegenerative, Medical and Health Sciences, ddc:616.89, Mice, 0302 clinical medicine, Malaltia de Parkinson, Monoaminergic, Eating Disorders Working Group of the Psychiatric Genomics Consortium, 2.1 Biological and endogenous factors, Aetiology, Cervell, ALZHEIMERS, NEURONS, Animals, Brain, Genome-Wide Association Study, Humans, Neurons, Parkinson Disease, Transcriptome, 11 Medical and Health Sciences, Genetics & Heredity, 0303 health sciences, Parkinson Disease/etiology/genetics/pathology, HERITABILITY, International Headache Genetics Consortium, Biological Sciences, Transcriptome/genetics, medicine.anatomical_structure, Neurological, Genome-Wide Association Study/methods, Alzheimer's disease, Life Sciences & Biomedicine, Gens, Cell type, TISSUES, 1.1 Normal biological development and functioning, Biology, IMMUNITY, 23andMe Research Team, Article, 03 medical and health sciences, ENTERIC NERVOUS-SYSTEM, SDG 3 - Good Health and Well-being, Underpinning research, medicine, Genetics, Brain/pathology, GENOME-WIDE ASSOCIATION, NUCLEUS, METAANALYSIS, 030304 developmental biology, Science & Technology, Neurons/pathology, Human Genome, Neurosciences, 06 Biological Sciences, medicine.disease, RISK LOCI, Brain Disorders, Genes, Enteric nervous system, Neuroscience, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. Eating Disorders Working Group of the Psychiatric Genomics Consortium Roger Adan17,18,19, Lars Alfredsson20, Tetsuya Ando21, Ole Andreassen22, Jessica Baker9, Andrew Bergen23,24, Wade Berrettini25, Andreas Birgegård26,27, Joseph Boden28, Ilka Boehm29, Claudette Boni30, Vesna Boraska Perica31,32, Harry Brandt33, Gerome Breen13,14, Julien Bryois1, Katharina Buehren34, Cynthia Bulik1,9,15, Roland Burghardt35, Matteo Cassina36, Sven Cichon37, Maurizio Clementi36, Jonathan Coleman13,14, Roger Cone38, Philippe Courtet39, Steven Crawford33, Scott Crow40, James Crowley16,26, unna Danner18, Oliver Davis41,42, Martina de Zwaan43, George Dedoussis44, Daniela Degortes45, Janiece DeSocio46, Danielle Dick47, Dimitris Dikeos48, Christian Dina49,50, Monika Dmitrzak-Weglarz51, Elisa Docampo Martinez52,53,54, Laramie Duncan55, Karin Egberts56, Stefan Ehrlich29, Geòrgia Escaramís52,53,54, Tõnu Esko57,58, Xavier Estivill52,53,54,59, Anne Farmer13, Angela Favaro45, Fernando Fernández-Aranda60,61, Manfred Fichter62,63, Krista Fischer57, Manuel Föcker64, Lenka Foretova65, Andreas Forstner37,66,67,68,69, Monica Forzan36, Christopher Franklin31, Steven Gallinger70, Héléna Gaspar13,14, Ina Giegling71, Johanna Giuranna64, Paola Giusti-Rodríquez16, Fragiskos Gonidakis72, Scott Gordon73, Philip Gorwood30,74, Monica Gratacos Mayora52,53,54, Jakob Grove75,76,77,78, Sébastien Guillaume39, Yiran Guo79, Hakon Hakonarson79,80, Katherine Halmi81, Ken Hanscombe82, Konstantinos Hatzikotoulas31, Joanna Hauser83, Johannes Hebebrand64, Sietske Helder13,84, Anjali Henders85, Stefan Herms37,69, Beate Herpertz-Dahlmann34, Wolfgang Herzog86, Anke Hinney64, L. John Horwood28, Christopher Hübel1,13, Laura Huckins31,87, James Hudson88, Hartmut Imgart89, Hidetoshi Inoko90, Vladimir Janout91, Susana Jiménez-Murcia60,61, Craig Johnson92, Jennifer Jordan93,94, Antonio Julià95, Anders Juréus1, Gursharan Kalsi13, Deborah Kaminská96, Allan Kaplan97, Jaakko Kaprio98,99, Leila Karhunen100, Andreas Karwautz101, Martien Kas17,102, Walter Kaye103, James Kennedy97, Martin Kennedy104, Anna Keski-Rahkonen98, Kirsty Kiezebrink105, Youl-Ri Kim106, Katherine Kirk73, Lars Klareskog107, Kelly Klump108, Gun Peggy Knudsen109, Maria La Via9, Mikael Landén1,19, Janne Larsen76,110,111, Stephanie Le Hellard112,113,114, Virpi Leppä1, Robert Levitan115, Dong Li79, Paul Lichtenstein1, Lisa Lilenfeld116, Bochao Danae Lin17, Jolanta Lissowska117, Jurjen Luykx17, Pierre Magistretti118,119, Mario Maj120, Katrin Mannik57,121, Sara Marsal95, Christian Marshall122, Nicholas Martin73, Manuel Mattheisen26,27,75,123, Morten Mattingsdal22, Sara McDevitt124,125, Peter McGuffin13, Sarah Medland73, Andres Metspalu57,126, Ingrid Meulenbelt127, Nadia Micali128,129, James Mitchell130, Karen Mitchell131, Palmiero Monteleone132, Alessio Maria Monteleone120, Grant Montgomery73,85,133, Preben Bo Mortensen76,110,111, Melissa Munn-Chernoff9, Benedetta Nacmias134, Marie Navratilova65, Claes Norring26,27, Ioanna Ntalla44, Catherine Olsen73, Roel Ophoff17,135, Julie O’Toole136, Leonid Padyukov107, Aarno Palotie58,99,137, Jacques Pantel30, Hana Papezova96, Richard Parker73, John Pearson138, Nancy Pedersen1, Liselotte Petersen76,110,111, Dalila Pinto87, Kirstin Purves13, Raquel Rabionet139,140,141, Anu Raevuori98, Nicolas Ramoz30, Ted Reichborn-Kjennerud109,142, Valdo Ricca134,143, Samuli Ripatti144, Stephan Ripke145,146,147, Franziska Ritschel29,148, Marion Roberts13, Alessandro Rotondo149, Dan Rujescu62,71, Filip Rybakowski150, Paolo Santonastaso151, André Scherag152, Stephen Scherer153, ulrike Schmidt13, Nicholas Schork154, Alexandra Schosser155, Jochen Seitz34, Lenka Slachtova156, P. Eline Slagboom127, Margarita Slof-Op ‘t Landt157,158, Agnieszka Slopien159, Sandro Sorbi134,160, Michael Strober161,162, Garret Stuber9,163, Patrick Sullivan1,16, Beata Świątkowska164, Jin Szatkiewicz16, Ioanna Tachmazidou31, Elena Tenconi45, Laura Thornton9, Alfonso Tortorella165,166, Federica Tozzi167, Janet Treasure13, Artemis Tsitsika168, Marta Tyszkiewicz-Nwafor150, Konstantinos Tziouvas169, Annemarie van Elburg18,170, Eric van Furth157,158, Tracey Wade171, Gudrun Wagner101, Esther Walton29, Hunna Watson9,10,11, Thomas Werge172, David Whiteman73, Elisabeth Widen99, D. Blake Woodside173,174, Shuyang Yao1, Zeynep Yilmaz9,16, Eleftheria Zeggini31,175, Stephanie Zerwas9 and Stephan Zipfel176 17Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands. 18Center for Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, the Netherlands. 19Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 20Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 21Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan. 22NORMENT KG Jebsen Centre, Division of Mental Health and Addiction, University of Oslo, Oslo University Hospital, Oslo, Norway. 23BioRealm, LLC, Walnut, CA, USA. 24Oregon Research Institute, Eugene, OR, USA. 25Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 26Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 27Center for Psychiatry Research, Stockholm Health Care Services, Stockholm City Council, Stockholm, Sweden. 28Christchurch Health and Development Study, University of Otago, Christchurch, New Zealand. 29Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. 30INSERM U894, Centre of Psychiatry and Neuroscience, Paris, France. 31Wellcome Sanger Institute, Hinxton, Cambridge, UK. 32Department of Medical Biology, School of Medicine, University of Split, Split, Croatia. 33The Center for Eating Disorders at Sheppard Pratt, Baltimore, MD, USA. 34Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, Germany. 35Klinikum Frankfurt/Oder, Frankfurt, Germany. 36Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padua, Italy. 37Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. 38Life Sciences Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. 39Department of Emergency Psychiatry and Post-Acute Care, CHRU Montpellier, University of Montpellier, Montpellier, France. 40Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA. 41MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. 42School of Social and Community Medicine, University of Bristol, Bristol, UK. 43Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany. 44Department of Nutrition and Dietetics, Harokopio University, Athens, Greece. 45Department of Neurosciences, University of Padova, Padua, Italy. 46College of Nursing, Seattle University, Seattle, WA, USA. 47Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA. 48Department of Psychiatry, Athens University Medical School, Athens University, Athens, Greece. 49L’institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France. 50L’institut du thorax, CHU Nantes, Nantes, France. 51Department of Psychiatric Genetics, Poznań University of Medical Sciences, Poznań, Poland. 52Barcelona Institute of Science and Technology, Barcelona, Spain. 53Universitat Pompeu Fabra, Barcelona, Spain. 54Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. 55Department of Psychiatry and Behavioral Sciences, Stanford University Stanford, CA, USA. 56Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health, Würzburg, Germany. 57Estonian Genome Center, University of Tartu, Tartu, Estonia. 58Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA. 59Genomics and Disease, Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona, Spain. 60Department of Psychiatry, University Hospital of Bellvitge –IDIBELL and CIBERobn, Barcelona, Spain. 61Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain. 62Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University (LMU), Munich, Germany. 63Schön Klinik Roseneck affiliated with the Medical Faculty of the University of Munich (LMU), Munich, Germany. 64Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 65Department of Cancer, Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. 66Institute of Human Genetics, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany. 67Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. 68Department of Psychiatry (UPK), University of Basel, Basel, Switzerland. 69Department of Biomedicine, University of Basel, Basel, Switzerland. 70Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 71Department of Psychiatry, Psychotherapy and Psychosomatics, Martin Luther University of Halle-Wittenberg, Halle, Germany. 721st Psychiatric Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece. 73QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. 74CMME (Groupe Hospitalier Sainte-Anne), Paris Descartes University, Paris, France. 75Department of Biomedicine, Aarhus University, Aarhus, Denmark. 76The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSyCH), Aarhus, Denmark. 77Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. 78Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark. 79Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA. 80Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 81Department of Psychiatry, Weill Cornell Medical College, New york, Ny, USA. 82Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, London, UK. 83Department of Adult Psychiatry, Poznań University of Medical Sciences, Poznań, Poland. 84Zorg op Orde, Leidschendam, the Netherlands. 85Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. 86Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany. 87Department of Psychiatry, and Genetics and Genomics Sciences, Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New york, Ny, USA. 88Biological Psychiatry Laboratory, McLean Hospital/Harvard Medical School, Boston, MA, USA. 89Eating Disorders Unit, Parklandklinik, Bad Wildungen, Germany. 90Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, Isehara, Japan. 91Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic. 92Eating Recovery Center, Denver, CO, USA. 93Department of Psychological Medicine, University of Otago, Christchurch, New Zealand. 94Canterbury District Health Board, Christchurch, New Zealand. 95Rheumatology Research Group, Vall d’Hebron Research Institute, Barcelona, Spain. 96Department of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic. 97Center for Addiction and Mental Health, Department of Psychiatry, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 98Department of Public Health, University of Helsinki, Helsinki, Finland. 99Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland. 100Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. 101Eating Disorders Unit, Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria. 102Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands. 103Department of Psychiatry, University of California San Diego, San Diego, CA, USA. 104Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand. 105Health Services Research Unit, University of Aberdeen, Aberdeen, UK. 106Department of Psychiatry, Seoul Paik Hospital, Inje University, Seoul, Korea. 107Rheumatology Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. 108Department of Psychology, Michigan State University, East Lansing, MI, USA. 109Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway. 110National Centre for Register-Based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark. 111Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Aarhus, Denmark. 112Department of Clinical Science, K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), University of Bergen, Bergen, Norway. 113Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. 114Department of Clinical Medicine, Laboratory Building, Haukeland University Hospital, Bergen, Norway. 115Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. 116American School of Professional Psychology, Argosy University, Northern Virginia, Arlington, VA, USA. 117Department of Cancer Epidemiology and Prevention, M Skłodowska-Curie Cancer Center - Oncology Center, Warsaw, Poland. 118BESE Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia. 119Department of Psychiatry, University of Lausanne-University Hospital of Lausanne (UNIL-CHUV), Lausanne, Switzerland. 120Department of Psychiatry, University of Campania ‘Luigi Vanvitelli’, Naples, Italy. 121Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. 122Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada. 123Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany. 124Department of Psychiatry, University College Cork, Cork, Ireland. 125Eist Linn Adolescent Unit, Bessborough, Health Service Executive South, Cork, Ireland. 126Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. 127Molecular Epidemiology Section (Department of Medical Statistics), Leiden University Medical Centre, Leiden, the Netherlands. 128Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 129Division of Child and Adolescent Psychiatry, Geneva University Hospital, Geneva, Switzerland. 130Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, Fargo, ND, USA. 131National Center for PTSD, VA Boston Healthcare System, Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. 132Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, Salerno, Italy. 133Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. 134Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy. 135Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA. 136Kartini Clinic, Portland, OR, USA. 137Center for Human Genome Research at the Massachusetts General Hospital, Boston, MA, USA. 138Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand. 139Saint Joan de Déu Research Institute, Saint Joan de Déu Barcelona Children’s Hospital, Barcelona, Spain. 140Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain. 141Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain. 142Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 143Department of Health Science, University of Florence, Florence, Italy. 144Department of Biometry, University of Helsinki, Helsinki, Finland. 145Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. 146Stanley Center for Psychiatric Research, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA. 147Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany. 148Eating Disorders Research and Treatment Center, Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. 149Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Pisa, Italy. 150Department of Psychiatry, Poznań University of Medical Sciences, Poznań, Poland. 151Department of Neurosciences, Padua Neuroscience Center, University of Padova, Padua, Italy. 152Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany. 153Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 154J. Craig Venter Institute (JCVI), La Jolla, CA, USA. 155Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. 156Department of Pediatrics and Center of Applied Genomics, First Faculty of Medicine, Charles University, Prague, Czech Republic. 157Center for Eating Disorders Ursula, Rivierduinen, Leiden, the Netherlands. 158Department of Psychiatry, Leiden University Medical Centre, Leiden, the Netherlands. 159Department of Child and Adolescent Psychiatry, Poznań University of Medical Sciences, Poznań, Poland. 160IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy. 161Department of Psychiatry and Biobehavioral Science, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA. 162David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. 163Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 164Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland. 165Department of Psychiatry, University of Naples SUN, Naples, Italy. 166Department of Psychiatry, University of Perugia, Perugia, Italy. 167Brain Sciences Department, Stremble Ventures, Limassol, Cyprus. 168Adolescent Health Unit, Second Department of Pediatrics, ‘P. & A. Kyriakou’ Children’s Hospital, University of Athens, Athens, Greece. 169Pediatric Intensive Care Unit, ‘P. & A. Kyriakou’ Children’s Hospital, University of Athens, Athens, Greece. 170Faculty of Social and Behavioral Sciences, Utrecht University, Utrecht, the Netherlands. 171School of Psychology, Flinders University, Adelaide, South Australia, Australia. 172Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 173Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 174Toronto General Hospital, Toronto, Ontario, Canada. 175Institute of Translational Genomics, Helmholtz Zentrum München, Neuherberg, Germany. 176Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Medical Hospital Tübingen, Tübingen, Germany International Headache Genetics Consortium Verneri Anttila177, Ville Artto178, Andrea Carmine Belin179, Irene de Boer180, Dorret I. Boomsma181, Sigrid Børte182, Daniel I. Chasman183, Lynn Cherkas184, Anne Francke Christensen185, Bru Cormand186, Ester Cuenca-Leon177, George Davey-Smith187, Martin Dichgans188, Cornelia van Duijn189, Tonu Esko57, Ann Louise Esserlind190, Michel Ferrari180, Rune R. Frants180, Tobias Freilinger191, Nick Furlotte192, Padhraig Gormley177, Lyn Griffiths193, Eija Hamalainen194, Thomas Folkmann Hansen6, Marjo Hiekkala195, M. Arfan Ikram189, Andres Ingason196, Marjo-Riitta Järvelin197, Risto Kajanne194, Mikko Kallela178, Jaakko Kaprio98,99, Mari Kaunisto195, Lisette J. A. Kogelman6, Christian Kubisch198, Mitja Kurki177, Tobias Kurth199, Lenore Launer200, Terho Lehtimaki201, Davor Lessel198, Lannie Ligthart181, Nadia Litterman192, Arn van den Maagdenberg180, Alfons Macaya202, Rainer Malik188, Massimo Mangino184, George McMahon187, Bertram Muller-Myhsok203, Benjamin M. Neale177, Carrie Northover192, Dale R. Nyholt193, Jes Olesen190, Aarno Palotie58,99,137, Priit Palta194, Linda Pedersen182, Nancy Pedersen1, Danielle Posthuma181, Patricia Pozo-Rosich204, Alice Pressman205, Olli Raitakari206, Markus Schürks199, Celia Sintas186, Kari Stefansson196, Hreinn Stefansson196, Stacy Steinberg196, David Strachan207, Gisela Terwindt180, Marta Vila-Pueyo202, Maija Wessman195, Bendik S. Winsvold182, Huiying Zhao193 and John Anker Zwart182 177Broad Institute of MIT and Harvard, Cambridge, MA, USA. 178Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. 179Karolinska Institutet, Stockholm, Sweden. 180Leiden University Medical Centre, Leiden, the Netherlands. 181VU University, Amsterdam, the Netherlands. 182Oslo University Hospital and University of Oslo, Oslo, Norway. 183Harvard Medical School, Cambridge, MA, USA. 184Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. 185Danish Headache Center, Copenhagen University Hospital, Copenhagen, Denmark. 186University of Barcelona, Barcelona, Spain. 187Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK. 188Institute for Stroke and Dementia Research, Munich, Germany. 189Erasmus University Medical Centre, Rotterdam, the Netherlands. 190Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup, Denmark. 191University of Tübingen, Tübingen, Germany. 19223&Me Inc., Mountain View, CA, USA. 193Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. 194Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. 195Folkhälsan Institute of Genetics, Helsinki, Finland. 196Decode genetics Inc., Reykjavik, Iceland. 197University of Oulu, Biocenter Oulu, Finland. 198University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 199Harvard Medical School, Boston, MA, USA. 200National Institute on Aging, Bethesda, MD, USA. 201School of Medicine, University of Tampere, Tampere, Finland. 202Vall d’Hebron Research Institute, Barcelona, Spain. 203Max Planck Institute of Psychiatry, Munich, Germany. 204Headache Research Group, Universitat Autònoma de Barcelona, Barcelona, Spain. 205Sutter Health, Sacramento, CA, USA. 206Department of Medicine, University of Turku, Turku, Finland. 207Population Health Research Institute, St George’s University of London, London, UK. 23andMe Research Team Michelle Agee208, Babak Alipanahi208, Adam Auton208, Robert Bell208, Katarzyna Bryc208, Sarah Elson208, Pierre Fontanillas208, Nicholas Furlotte208, Karl Heilbron208, David Hinds208, Karen Huber208, Aaron Kleinman208, Nadia Litterman208, Jennifer McCreight208, Matthew McIntyre208, Joanna Mountain208, Elizabeth Noblin208, Carrie Northover208, Steven Pitts208, J. Sathirapongsasuti208, Olga Sazonova208, Janie Shelton208, Suyash Shringarpure208, Chao Tian208, Joyce Tung208, Vladimir Vacic208 and Catherine Wilson208 20823andMe, Inc., Mountain View, CA, US

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2020
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19. Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches

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Yao, S., Kuja-Halkola, R., Martin, J., Lu, Y., Lichtenstein, P., Hubel, C., Almqvist, C., Magnusson, P. K., Bulik, C. M., Larsson, H., Norring, C., Birgegard, A., Yilmaz, Z., Watson, H., Baker, J., Thornton, L. M., Adan, R., Ando, T., Bergen, A., Berrettini, W., Boni, C., Boraska Perica, V., Brandt, H., Burghardt, R., Cassina, M., Cesta, C., Clementi, M., Coleman, J., Cone, R., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U., Davis, O., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J., Dick, D., Dikeos, D., Dmitrzak-Weglarz, M., Docampo, E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Favaro, A., Fernandez-Aranda, F., Fichter, M., Finan, C., Fischer, K., Focker, M., Foretova, L., Forzan, M., Franklin, C., Gaspar, H., Gonidakis, F., Gorwood, P., Gratacos, M., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S., Hendriks, J., Herpertz-Dahlmann, B., Herzog, W., Hilliard, C., Hinney, A., Huckins, L., Hudson, J., Huemer, J., Imgart, H., Inoko, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Jureus, A., Kalsi, G., Kaminska, D., Kaplan, A., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M., Kaye, W., Kennedy, J., Kennedy, M., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K., Knudsen, G. P., Koeleman, B., Koubek, D., La Via, M., Landen, M., Levitan, R., Li, D., Lilenfeld, L., Lissowska, J., Magistretti, P., Maj, M., Mannik, K., Martin, N., Mcdevitt, S., Mcguffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Mortensen, P., Munn-Chernoff, M., Nacmias, B., Nilsson, I., Ntalla, I., O'Toole, J., Pantel, J., Papezova, H., Parker, R., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Reichborn-Kjennerud, T., Ricca, V., Ripke, S., Ritschel, F., Roberts, M., Rotondo, A., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M., Slopien, A., Smith, T., Sorbi, S., Strengman, E., Strober, M., Sullivan, P., Szatkiewicz, J., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Thornton, L., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tziouvas, K., van Elburg, A., van Furth, E., Wade, T., Wagner, G., Walton, E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Alfredsson, L., Andreassen, O., Aschauer, H., Barrett, J., Bencko, V., Carlberg, L., Cichon, S., Cohen-Woods, S., Dina, C., Ding, B., Espeseth, T., Floyd, J., Gallinger, S., Gambaro, G., Giegling, I., Herms, S., Janout, V., Julia, A., Klareskog, L., Le Hellard, S., Leboyer, M., Lundervold, A., Marsal, S., Mattingsdal, M., Navratilova, M., Ophoff, R., Palotie, A., Pinto, D., Ripatti, S., Rujescu, D., Scherer, S., Scott, L., Sladek, R., Soranzo, N., Southam, L., Steen, V., Wichmann, H. -E., Widen, E., Breen, G., Bulik, C., Yao, S., Kuja-Halkola, R., Martin, J., Lu, Y., Lichtenstein, P., Hubel, C., Almqvist, C., Magnusson, P. K., Bulik, C. M., Larsson, H., Norring, C., Birgegard, A., Yilmaz, Z., Watson, H., Baker, J., Thornton, L. M., Adan, R., Ando, T., Bergen, A., Berrettini, W., Boni, C., Boraska Perica, V., Brandt, H., Burghardt, R., Cassina, M., Cesta, C., Clementi, M., Coleman, J., Cone, R., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U., Davis, O., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J., Dick, D., Dikeos, D., Dmitrzak-Weglarz, M., Docampo, E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Favaro, A., Fernandez-Aranda, F., Fichter, M., Finan, C., Fischer, K., Focker, M., Foretova, L., Forzan, M., Franklin, C., Gaspar, H., Gonidakis, F., Gorwood, P., Gratacos, M., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S., Hendriks, J., Herpertz-Dahlmann, B., Herzog, W., Hilliard, C., Hinney, A., Huckins, L., Hudson, J., Huemer, J., Imgart, H., Inoko, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Jureus, A., Kalsi, G., Kaminska, D., Kaplan, A., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M., Kaye, W., Kennedy, J., Kennedy, M., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K., Knudsen, G. P., Koeleman, B., Koubek, D., La Via, M., Landen, M., Levitan, R., Li, D., Lilenfeld, L., Lissowska, J., Magistretti, P., Maj, M., Mannik, K., Martin, N., Mcdevitt, S., Mcguffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Mortensen, P., Munn-Chernoff, M., Nacmias, B., Nilsson, I., Ntalla, I., O'Toole, J., Pantel, J., Papezova, H., Parker, R., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Reichborn-Kjennerud, T., Ricca, V., Ripke, S., Ritschel, F., Roberts, M., Rotondo, A., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M., Slopien, A., Smith, T., Sorbi, S., Strengman, E., Strober, M., Sullivan, P., Szatkiewicz, J., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Thornton, L., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tziouvas, K., van Elburg, A., van Furth, E., Wade, T., Wagner, G., Walton, E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Alfredsson, L., Andreassen, O., Aschauer, H., Barrett, J., Bencko, V., Carlberg, L., Cichon, S., Cohen-Woods, S., Dina, C., Ding, B., Espeseth, T., Floyd, J., Gallinger, S., Gambaro, G., Giegling, I., Herms, S., Janout, V., Julia, A., Klareskog, L., Le Hellard, S., Leboyer, M., Lundervold, A., Marsal, S., Mattingsdal, M., Navratilova, M., Ophoff, R., Palotie, A., Pinto, D., Ripatti, S., Rujescu, D., Scherer, S., Scott, L., Sladek, R., Soranzo, N., Southam, L., Steen, V., Wichmann, H. -E., Widen, E., Breen, G., Bulik, C., Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff], 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), Oregon Research Institute (ORI), Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Stockholm County Council, Analyse Phenotypique, Developpementale et Genetique des Comportements Addictifs, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), University of Split, Azienda Ospedaliera di Padova, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Nutrition-Dietetics, Harokopio University of Athens, University of Athens Medical School [Athens], MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Medstar Research Institute, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, National and Kapodistrian University of Athens (NKUA), 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), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Weill Medical College of Cornell University [New York], Department of Genomics, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Universität Duisburg-Essen [Essen], Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Tokai University, Institute for Marine and Antarctic Studies [Horbat] (IMAS), University of Tasmania [Hobart, Australia] (UTAS), National Institute for Health and Welfare [Helsinki], Medizinische Universität Wien = Medical University of Vienna, University of California [San Diego] (UC San Diego), University of California, Psychiatric Neurogenetics Section, Centre for Addiction and Mental Health, School of Computing [Dublin], Dublin City University [Dublin] (DCU), University of Helsinki, University Medical Center [Utrecht], Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Oak Ridge National Laboratory [Oak Ridge] (ORNL), UT-Battelle, LLC, The M Sklodowska-Curie Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Università degli studi della Campania 'Luigi Vanvitelli', Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Queensland Institute of Medical Research, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, Estonian Genome and Medicine, University of Tartu, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, Università degli Studi di Salerno (UNISA), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Vanderbilt University School of Medicine [Nashville], Charles University [Prague] (CU), Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K, Norwegian Institute of Public Health [Oslo] (NIPH), Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Institute of Medical Informatics, Biometry and Epidemiology, The Scripps Translational Science Institute and The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, Leiden University Medical Center (LUMC), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, The Jackson Laboratory [Bar Harbor] (JAX), The Nofer Institute of Occupational Medicine, Università degli Studi di Perugia (UNIPG), 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)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department Biostatistics University of North Carolina, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Sachs' Children's Hospital, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Institute of Hygiene and Epidemiology, Charles University and General University Hospital-First Faculty of Medicine, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, 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), University of Oslo (UiO), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Department of Optics [Univ Palacký], Faculty of Science [Univ Palacký], Palacky University Olomouc-Palacky University Olomouc, Vall d'Hebron University Hospital [Barcelona], Rheumatology Unit, University of Bergen (UiB), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Masaryk Memorial Cancer Institute (RECAMO), Department of Psychiatry, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, 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), Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München (LMU)-Chair of Epidemiology, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Institute of Psychiatry-King‘s College London, Cardiff University-Medical Research Council, and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Adult, Male, Multifactorial Inheritance, Adolescent, behavioral disciplines and activities, Article, Feeding and Eating Disorders, Young Adult, [SCCO]Cognitive science, Polygenic risk score, Risk Factors, mental disorders, Humans, ADHD, Genetic epidemiology, Registries, Child, Sweden, [SDV.GEN]Life Sciences [q-bio]/Genetics, Eating disorder, Anorexia nervosa, Bulimia nervosa, Eating disorders, Attention Deficit Disorder with Hyperactivity, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

International audience; BACKGROUND:Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa.METHODS:We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472).RESULTS:Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes.CONCLUSIONS:We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.

Published
2019
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22. A meta-analysis and transmission disequilibrium study of association between the dopamine D3 receptor gene and schizophrenia

Author

Williams, J, Spurlock, G, Holmans, P, Mant, R, Murphy, K, Jones, L, Cardno, A, Asherson, P, Blackwood, D, Muir, W, Meszaros, K, Aschauer, H, Mallet, J, Laurent, C, Pekkarinen, P, Seppala, J, Stefanis, C N, Papadimitriou, G N, Macciardi, F, Verga, M, Pato, C, Azevedo, H, Crocq, M-A, Gurling, H, Kalsi, G, Curtis, D, McGuffin, P, and Owen, M J

Published
1998
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24. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

Author

Bryois, J. Skene, N.G. Hansen, T.F. Kogelman, L.J.A. Watson, H.J. Liu, Z. Adan, R. Alfredsson, L. Ando, T. Andreassen, O. Baker, J. Bergen, A. Berrettini, W. Birgegård, A. Boden, J. Boehm, I. Boni, C. Boraska Perica, V. Brandt, H. Breen, G. Bryois, J. Buehren, K. Bulik, C. Burghardt, R. Cassina, M. Cichon, S. Clementi, M. Coleman, J. Cone, R. Courtet, P. Crawford, S. Crow, S. Crowley, J. Danner, U. Davis, O. de Zwaan, M. Dedoussis, G. Degortes, D. DeSocio, J. Dick, D. Dikeos, D. Dina, C. Dmitrzak-Weglarz, M. Docampo Martinez, E. Duncan, L. Egberts, K. Ehrlich, S. Escaramís, G. Esko, T. Estivill, X. Farmer, A. Favaro, A. Fernández-Aranda, F. Fichter, M. Fischer, K. Föcker, M. Foretova, L. Forstner, A. Forzan, M. Franklin, C. Gallinger, S. Gaspar, H. Giegling, I. Giuranna, J. Giusti-Rodríquez, P. Gonidakis, F. Gordon, S. Gorwood, P. Gratacos Mayora, M. Grove, J. Guillaume, S. Guo, Y. Hakonarson, H. Halmi, K. Hanscombe, K. Hatzikotoulas, K. Hauser, J. Hebebrand, J. Helder, S. Henders, A. Herms, S. Herpertz-Dahlmann, B. Herzog, W. Hinney, A. Horwood, L.J. Hübel, C. Huckins, L. Hudson, J. Imgart, H. Inoko, H. Janout, V. Jiménez-Murcia, S. Johnson, C. Jordan, J. Julià, A. Juréus, A. Kalsi, G. Kaminská, D. Kaplan, A. Kaprio, J. Karhunen, L. Karwautz, A. Kas, M. Kaye, W. Kennedy, J. Kennedy, M. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Kirk, K. Klareskog, L. Klump, K. Knudsen, G.P. La Via, M. Landén, M. Larsen, J. Le Hellard, S. Leppä, V. Levitan, R. Li, D. Lichtenstein, P. Lilenfeld, L. Lin, B.D. Lissowska, J. Luykx, J. Magistretti, P. Maj, M. Mannik, K. Marsal, S. Marshall, C. Martin, N. Mattheisen, M. Mattingsdal, M. McDevitt, S. McGuffin, P. Medland, S. Metspalu, A. Meulenbelt, I. Micali, N. Mitchell, J. Mitchell, K. Monteleone, P. Monteleone, A.M. Montgomery, G. Mortensen, P.B. Munn-Chernoff, M. Nacmias, B. Navratilova, M. Norring, C. Ntalla, I. Olsen, C. Ophoff, R. O’Toole, J. Padyukov, L. Palotie, A. Pantel, J. Papezova, H. Parker, R. Pearson, J. Pedersen, N. Petersen, L. Pinto, D. Purves, K. Rabionet, R. Raevuori, A. Ramoz, N. Reichborn-Kjennerud, T. Ricca, V. Ripatti, S. Ripke, S. Ritschel, F. Roberts, M. Rotondo, A. Rujescu, D. Rybakowski, F. Santonastaso, P. Scherag, A. Scherer, S. Schmidt, U. Schork, N. Schosser, A. Seitz, J. Slachtova, L. Slagboom, P.E. Slof-Op ‘t Landt, M. Slopien, A. Sorbi, S. Strober, M. Stuber, G. Sullivan, P. Świątkowska, B. Szatkiewicz, J. Tachmazidou, I. Tenconi, E. Thornton, L. Tortorella, A. Tozzi, F. Treasure, J. Tsitsika, A. Tyszkiewicz-Nwafor, M. Tziouvas, K. van Elburg, A. van Furth, E. Wade, T. Wagner, G. Walton, E. Watson, H. Werge, T. Whiteman, D. Widen, E. Woodside, D.B. Yao, S. Yilmaz, Z. Zeggini, E. Zerwas, S. Zipfel, S. Anttila, V. Artto, V. Belin, A.C. de Boer, I. Boomsma, D.I. Børte, S. Chasman, D.I. Cherkas, L. Christensen, A.F. Cormand, B. Cuenca-Leon, E. Davey-Smith, G. Dichgans, M. van Duijn, C. Esko, T. Esserlind, A.L. Ferrari, M. Frants, R.R. Freilinger, T. Furlotte, N. Gormley, P. Griffiths, L. Hamalainen, E. Hiekkala, M. Ikram, M.A. Ingason, A. Järvelin, M.-R. Kajanne, R. Kallela, M. Kaprio, J. Kaunisto, M. Kogelman, L.J.A. Kubisch, C. Kurki, M. Kurth, T. Launer, L. Lehtimaki, T. Lessel, D. Ligthart, L. Litterman, N. Maagdenberg, A. Macaya, A. Malik, R. Mangino, M. McMahon, G. Muller-Myhsok, B. Neale, B.M. Northover, C. Nyholt, D.R. Olesen, J. Palotie, A. Palta, P. Pedersen, L. Pedersen, N. Posthuma, D. Pozo-Rosich, P. Pressman, A. Raitakari, O. Schürks, M. Sintas, C. Stefansson, K. Stefansson, H. Steinberg, S. Strachan, D. Terwindt, G. Vila-Pueyo, M. Wessman, M. Winsvold, B.S. Zhao, H. Zwart, J.A. Agee, M. Alipanahi, B. Auton, A. Bell, R. Bryc, K. Elson, S. Fontanillas, P. Furlotte, N. Heilbron, K. Hinds, D. Huber, K. Kleinman, A. Litterman, N. McCreight, J. McIntyre, M. Mountain, J. Noblin, E. Northover, C. Pitts, S. Sathirapongsasuti, J. Sazonova, O. Shelton, J. Shringarpure, S. Tian, C. Tung, J. Vacic, V. Wilson, C. Brueggeman, L. Bulik, C.M. Arenas, E. Hjerling-Leffler, J. Sullivan, P.F. International Headache Genetics Consortium Eating Disorders Working Group of the Psychiatric Genomics Consortium

Abstract

Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

Published
2020

31. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Author

Watson, H.J., Yilmaz, Z., Thorntont, L.M., Hubel, C., Coleman, J.R.I., Gaspar, H.A., Bryois, J., Hinney, A., Leppa, V.M., Mattheisen, M., Medland, S.E., Ripke, S., Yao, S.Y., Giusti-Rodriguez, P., Hanscombe, K.B., Purves, K.L., Adan, R.A.H., Alfredsson, L., Ando, T., Andreassen, O.A., Baker, J.H., Berrettini, W.H., Boehm, I., Boni, C., Perica, V.B., 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., Zwaan, M. de, 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., Eskos, 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., Mayora, M.G., Guillaume, S., Guo, Y.R., 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., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M.J.H., Kennedy, J.L., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y.R., Klareskog, L., Klump, K.L., Knudsen, G.P.S., Via, M.C. la, Hellard, S. le, 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., Munn-Chernoff, M.A., 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., Landt, M.C.T.S.O. '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., Elbur, A.A. van, Furth, E.F. van, 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.E., Olsen, C.M., Pearson, J.F., Pedersen, N.L., Strober, M., Werge, T., Whiteman, D.C., Woodside, D.B., Stuber, G.D., Gordon, S., Grove, J., Henders, A.K., Jureus, A., Kirk, K.M., Larsen, J.T., Parker, R., Petersen, L., Jordan, J., Kennedy, M., Montgomery, G.W., Wade, T.D., Birgegard, A., Lichtenstein, P., Norring, C., Landen, M., Martin, N.G., Mortensen, P.B., Sullivan, P.F., Breen, G., Bulik, C.M., Anorexia Nervosa Genetics Initiati, and Psychiat Genomics Consortium

Published
2019

35. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

Author

Bryois, J. Skene, N.G. Hansen, T.F. Kogelman, L.J.A. Watson, H.J. Liu, Z. Adan, R. Alfredsson, L. Ando, T. Andreassen, O. Baker, J. Bergen, A. Berrettini, W. Birgegård, A. Boden, J. Boehm, I. Boni, C. Boraska Perica, V. Brandt, H. Breen, G. Bryois, J. Buehren, K. Bulik, C. Burghardt, R. Cassina, M. Cichon, S. Clementi, M. Coleman, J. Cone, R. Courtet, P. Crawford, S. Crow, S. Crowley, J. Danner, U. Davis, O. de Zwaan, M. Dedoussis, G. Degortes, D. DeSocio, J. Dick, D. Dikeos, D. Dina, C. Dmitrzak-Weglarz, M. Docampo Martinez, E. Duncan, L. Egberts, K. Ehrlich, S. Escaramís, G. Esko, T. Estivill, X. Farmer, A. Favaro, A. Fernández-Aranda, F. Fichter, M. Fischer, K. Föcker, M. Foretova, L. Forstner, A. Forzan, M. Franklin, C. Gallinger, S. Gaspar, H. Giegling, I. Giuranna, J. Giusti-Rodríquez, P. Gonidakis, F. Gordon, S. Gorwood, P. Gratacos Mayora, M. Grove, J. Guillaume, S. Guo, Y. Hakonarson, H. Halmi, K. Hanscombe, K. Hatzikotoulas, K. Hauser, J. Hebebrand, J. Helder, S. Henders, A. Herms, S. Herpertz-Dahlmann, B. Herzog, W. Hinney, A. Horwood, L.J. Hübel, C. Huckins, L. Hudson, J. Imgart, H. Inoko, H. Janout, V. Jiménez-Murcia, S. Johnson, C. Jordan, J. Julià, A. Juréus, A. Kalsi, G. Kaminská, D. Kaplan, A. Kaprio, J. Karhunen, L. Karwautz, A. Kas, M. Kaye, W. Kennedy, J. Kennedy, M. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Kirk, K. Klareskog, L. Klump, K. Knudsen, G.P. La Via, M. Landén, M. Larsen, J. Le Hellard, S. Leppä, V. Levitan, R. Li, D. Lichtenstein, P. Lilenfeld, L. Lin, B.D. Lissowska, J. Luykx, J. Magistretti, P. Maj, M. Mannik, K. Marsal, S. Marshall, C. Martin, N. Mattheisen, M. Mattingsdal, M. McDevitt, S. McGuffin, P. Medland, S. Metspalu, A. Meulenbelt, I. Micali, N. Mitchell, J. Mitchell, K. Monteleone, P. Monteleone, A.M. Montgomery, G. Mortensen, P.B. Munn-Chernoff, M. Nacmias, B. Navratilova, M. Norring, C. Ntalla, I. Olsen, C. Ophoff, R. O’Toole, J. Padyukov, L. Palotie, A. Pantel, J. Papezova, H. Parker, R. Pearson, J. Pedersen, N. Pete and Bryois, J. Skene, N.G. Hansen, T.F. Kogelman, L.J.A. Watson, H.J. Liu, Z. Adan, R. Alfredsson, L. Ando, T. Andreassen, O. Baker, J. Bergen, A. Berrettini, W. Birgegård, A. Boden, J. Boehm, I. Boni, C. Boraska Perica, V. Brandt, H. Breen, G. Bryois, J. Buehren, K. Bulik, C. Burghardt, R. Cassina, M. Cichon, S. Clementi, M. Coleman, J. Cone, R. Courtet, P. Crawford, S. Crow, S. Crowley, J. Danner, U. Davis, O. de Zwaan, M. Dedoussis, G. Degortes, D. DeSocio, J. Dick, D. Dikeos, D. Dina, C. Dmitrzak-Weglarz, M. Docampo Martinez, E. Duncan, L. Egberts, K. Ehrlich, S. Escaramís, G. Esko, T. Estivill, X. Farmer, A. Favaro, A. Fernández-Aranda, F. Fichter, M. Fischer, K. Föcker, M. Foretova, L. Forstner, A. Forzan, M. Franklin, C. Gallinger, S. Gaspar, H. Giegling, I. Giuranna, J. Giusti-Rodríquez, P. Gonidakis, F. Gordon, S. Gorwood, P. Gratacos Mayora, M. Grove, J. Guillaume, S. Guo, Y. Hakonarson, H. Halmi, K. Hanscombe, K. Hatzikotoulas, K. Hauser, J. Hebebrand, J. Helder, S. Henders, A. Herms, S. Herpertz-Dahlmann, B. Herzog, W. Hinney, A. Horwood, L.J. Hübel, C. Huckins, L. Hudson, J. Imgart, H. Inoko, H. Janout, V. Jiménez-Murcia, S. Johnson, C. Jordan, J. Julià, A. Juréus, A. Kalsi, G. Kaminská, D. Kaplan, A. Kaprio, J. Karhunen, L. Karwautz, A. Kas, M. Kaye, W. Kennedy, J. Kennedy, M. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Kirk, K. Klareskog, L. Klump, K. Knudsen, G.P. La Via, M. Landén, M. Larsen, J. Le Hellard, S. Leppä, V. Levitan, R. Li, D. Lichtenstein, P. Lilenfeld, L. Lin, B.D. Lissowska, J. Luykx, J. Magistretti, P. Maj, M. Mannik, K. Marsal, S. Marshall, C. Martin, N. Mattheisen, M. Mattingsdal, M. McDevitt, S. McGuffin, P. Medland, S. Metspalu, A. Meulenbelt, I. Micali, N. Mitchell, J. Mitchell, K. Monteleone, P. Monteleone, A.M. Montgomery, G. Mortensen, P.B. Munn-Chernoff, M. Nacmias, B. Navratilova, M. Norring, C. Ntalla, I. Olsen, C. Ophoff, R. O’Toole, J. Padyukov, L. Palotie, A. Pantel, J. Papezova, H. Parker, R. Pearson, J. Pedersen, N. Pete

Abstract

Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

Published
2020

36. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Author

Huckins, L. M., Hatzikotoulas, K., Curtis, C., Esko, T., Espeseth, T., Estivill, X., Favaro, A., Fernández-Aranda, F., Fichter, M. M., Finan, C., Fischer, K., Floyd, J. A. B., Foretova, L., Rhodes, D., Forzan, M., Franklin, C. S., Gallinger, S., Gambaro, G., Gaspar, H. A., Giegling, I., Gonidakis, F., Gorwood, P., Gratacos, M., Guillaume, S., Moens, J., Guo, Y., Hakonarson, H., Halmi, K. A., Hauser, J., Hebebrand, J., Helder, S., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Kalsi, G., Hilliard, C. E., Hinney, A., Hübel, C., Hudson, J. I., Huemer, J., Inoko, H., Janout, V., Jiménez-Murcia, S., Johnson, C., Dempster, D., Julià, A., Juréus, A., Kaminska, D., Kaplan, A. S., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M. J. H., Kaye, W., Leung, R., Kennedy, J. L., Keski-Rahkonen, A., Kiezebrink, K., Klareskog, L., Klump, K. L., Knudsen, G. P. S., Koeleman, B. P. C., Koubek, D., La Via, M. C., Landén, M., Keohane, A., Le Hellard, S., Levitan, R. D., Li, D., Lichtenstein, P., Lilenfeld, L., Lissowska, J., Lundervold, A., Magistretti, P., Maj, M., Mannik, K., Burghardt, R., Marsal, S., Martin, N., Mattingsdal, M., McDevitt, S., McGuffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Ehrlich, S., Mitchell, K., Monteleone, P., Monteleone, A. M., Mortensen, P., Munn-Chernoff, M. A., Navratilova, M., Nilsson, I., Norring, C., Ntalla, I., Ophoff, R. A., O'Toole, J. K., Palotie, A., Pante, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Southam, L., Reichborn-Kjennerud, T., Ripatti, S., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schmidt, U., Ludolph, A., Schork, N. J., Schosser, A., Slachtova, L., Sladek, R., Slagboom, P. E., Slof-Op 't Landt, M. C. T., Slopien, A., Soranzo, N., Steen, V. M., Walton, E., Strengman, E., Strober, M., Sullivan, P. F., Szatkiewicz, J. P., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Thornton, L. M., Tortorella, A., Tozzi, F., Deloukas, P., Treasure, J., Tsitsika, A., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wagner, G., Watson, H., Wichmann, H-E, Widen, E., Hofman, A., Woodside, D. B., Yanovski, J., Yao, S., Yilmaz, Z., Zeggini, E., Zerwas, S., Zipfel, S., Palta, P., van Rooij, F. J. A., Stirrups, K., Adan, R., Boni, C., Cone, R., Dedoussis, G., van Furth, E., Hudson, J., Kas, M., Keski-Rahonen, A., Steinberg, J., Knudsen, G-P, Raevuori, A. H., Aguilera-McKay, F., van Elburg, A., Consortium, Eating Disorder Working Group of the Psychiatric Genomics, Collier, D. A., Breen, G., Bulik, C. M., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Aschauer, H., Baker, J. H., Barrett, J. C., Bencko, V., Bergen, A. W., Berrettini, W. H., Birgegard, A., Boraska Perica, V., Brandt, H., Carlberg, L., Cassina, M., Cichon, S., Clementi, M., Cohen-Woods, S., Coleman, J., Cone, R. D., Gunasinghe, C., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Degortes, D., DeSocio, J. E., Romero, A., Dick, D. M., Dikeos, D., Dina, C., Ding, B., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L., Egberts, K., Escaramís, G., Inconnu, Institut Pasteur de Côte d'Ivoire, Réseau International des Instituts Pasteur (RIIP), Laboratoire de bactériologie-virologie, CHU de Yopougon, Department of Nutrition Science & Dietetics, Harokopio University, Analyse Phenotypique, Developpementale et Genetique des Comportements Addictifs, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Clinicum, University of Helsinki, Department of Public Health, Anna Keski-Rahkonen / Principal Investigator, HUS Children and Adolescents, Genomics of Neurological and Neuropsychiatric Disorders, Genetic Epidemiology, Eating Disorder Working Group of the Psychiatric Genomics Consortium, Epidemiology, Kas lab, Huckins, L. M., Hatzikotoulas, K., Southam, L., Thornton, L. M., Steinberg, J., Aguilera-Mckay, F., Treasure, J., Schmidt, U., Gunasinghe, C., Romero, A., Curtis, C., Rhodes, D., Moens, J., Kalsi, G., Dempster, D., Leung, R., Keohane, A., Burghardt, R., Ehrlich, S., Hebebrand, J., Hinney, A., Ludolph, A., Walton, E., Deloukas, P., Hofman, A., Palotie, A., Palta, P., van Rooij, F. J. A., Stirrups, K., Adan, R., Boni, C., Cone, R., Dedoussis, G., van Furth, E., Gonidakis, F., Gorwood, P., Hudson, J., Kaprio, J., Kas, M., Keski-Rahonen, A., Kiezebrink, K., Knudsen, G. -P., Slof-Op 'T Landt, M. C. T., Maj, M., Monteleone, A. M., Monteleone, P., Raevuori, A. H., Reichborn-Kjennerud, T., Tozzi, F., Tsitsika, A., Elburg, A., Collier, D. A., Sullivan, P. F., Breen, G., Bulik, C. M., Zeggini, E., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Aschauer, H., Baker, J. H., Barrett, J. C., Bencko, V., Bergen, A. W., Berrettini, W. H., Birgegard, A., Perica, V. B., Brandt, H., Carlberg, L., Cassina, M., Cichon, S., Clementi, M., Cohen-Woods, S., Coleman, J., Cone, R. D., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U. N., Davis, O. S. P., Zwaan, M., Degortes, D., Desocio, J. E., Dick, D. M., Dikeos, D., Dina, C., Ding, B., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L., Egberts, K., Escaramis, G., Esko, T., Espeseth, T., Estivill, X., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Finan, C., Fischer, K., Floyd, J. A. B., Foretova, L., Forzan, M., Franklin, C. S., Gallinger, S., Gambaro, G., Gaspar, H. A., Giegling, I., Gratacos, M., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K. A., Hauser, J., Helder, S., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Hilliard, C. E., Hubel, C., Hudson, J. I., Huemer, J., Inoko, H., Janout, V., Jimenez-Murcia, S., Johnson, C., Julia, A., Jureus, A., Kaminska, D., Kaplan, A. S., Karhunen, L., Karwautz, A., Kas, M. J. H., Kaye, W., Kennedy, J. L., Keski-Rahkonen, A., Klareskog, L., Klump, K. L., Knudsen, G. P. S., Koeleman, B. P. C., Koubek, D., Via, M. C. L., Landen, M., Hellard, S. L., Levitan, R. D., Li, D., Lichtenstein, P., Lilenfeld, L., Lissowska, J., Lundervold, A., Magistretti, P., Mannik, K., Marsal, S., Martin, N., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Mortensen, P., Munn-Chernoff, M. A., Navratilova, M., Nilsson, I., Norring, C., Ntalla, I., Ophoff, R. A., O'Toole, J. K., Pantel, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Ripatti, S., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schork, N. J., Schosser, A., Slachtova, L., Sladek, R., Slagboom, P. E., Slopien, A., Soranzo, N., Steen, V. M., Strengman, E., Strober, M., Szatkiewicz, J. P., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Tortorella, A., Tziouvas, K., Elburg, A. A., Furth, E. F., Wagner, G., Watson, H., Wichmann, H. -E., Widen, E., Woodside, D. B., Yanovski, J., Yao, S., Yilmaz, Z., Zerwas, S., and Zipfel, S.

Subjects
Male, 0301 basic medicine, Anorexia Nervosa, [SDV]Life Sciences [q-bio], Intron, Medizin, Genome-wide association study, Genome, 3124 Neurology and psychiatry, Intergenic region, Molecular Biology, Psychiatry and Mental Health, Cellular and Molecular Neuroscience, Exome, HYPOGONADOTROPIC HYPOGONADISM, GENE-EXPRESSION, Genetics, Bulimia nervosa, ASSOCIATION, GPI-Linked Protein, 3. Good health, CONTROLLED-TRIALS, Psychiatry and Mental health, Eating disorders, Phenotype, CONTROLLED FAMILY, Female, Original Article, Human, Genotype, In silico, European Continental Ancestry Group, Locus (genetics), Biology, GPI-Linked Proteins, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, BULIMIA-NERVOSA, medicine, Journal Article, Humans, Family, Genetic Predisposition to Disease, ddc:610, Genetic association, AUTISM SPECTRUM DISORDER, 3112 Neurosciences, Genetic Variation, Correction, EATING-DISORDERS, ARACHIDONIC-ACID, medicine.disease, Introns, 030104 developmental biology, Cell Adhesion Molecule, RISK-FACTORS, 3111 Biomedicine, Cell Adhesion Molecules, Genome-Wide Association Study
Abstract

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10−6), and rs7700147, an intergenic variant (P=2.93 × 10−5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Published
2017
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37. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Author

Watson HJ, Yilmaz Z, Thornton LM, Hübel C, Coleman JRI, Gaspar HA, Bryois J, Hinney A, Leppä VM, Mattheisen M, Medland SE, Ripke S, Yao S, Giusti-Rodríguez P, Anorexia Nervosa Genetics Initiative, Hanscombe KB, Purves KL, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Adan RAH, Alfredsson L, Ando T, Andreassen OA, Baker JH, Berrettini WH, Boehm I, Boni C, Perica VB, Buehren K, Burghardt R, Cassina M, Cichon S, Clementi M, Cone RD, Courtet P, Crow S, Crowley JJ, Danner UN, Davis OSP, de Zwaan M, Dedoussis G, Degortes D, DeSocio JE, Dick DM, Dikeos D, Dina C, Dmitrzak-Weglarz M, Docampo E, Duncan LE, Egberts K, Ehrlich S, Escaramís G, Esko T, Estivill X, Farmer A, Favaro A, Fernández-Aranda F, Fichter MM, Fischer K, Föcker M, Foretova L, Forstner AJ, Forzan M, Franklin CS, Gallinger S, Giegling I, Giuranna J, Gonidakis F, Gorwood P, Mayora MG, Guillaume S, Guo Y, Hakonarson H, Hatzikotoulas K, Hauser J, Hebebrand J, Helder SG, Herms S, Herpertz-Dahlmann B, Herzog W, Huckins LM, Hudson JI, Imgart H, Inoko H, Janout V, Jiménez-Murcia S, Julià A, Kalsi G, Kaminská D, Kaprio J, Karhunen L, Karwautz A, Kas MJH, Kennedy JL, Keski-Rahkonen A, Kiezebrink K, Kim YR, Klareskog L, Klump KL, Knudsen GPS, La Via MC, Le Hellard S, Levitan RD, Li D, Lilenfeld L, Lin BD, Lissowska J, Luykx J, Magistretti PJ, Maj M, Mannik K, Marsal S, Marshall CR, Mattingsdal M, McDevitt S, McGuffin P, Metspalu A, Meulenbelt I, Micali N, Mitchell K, Monteleone AM, Monteleone P, Munn-Chernoff MA, Nacmias B, Navratilova M, Ntalla I, O'Toole JK, Ophoff RA, Padyukov L, Palotie A, Pantel J, Papezova H, Pinto D, Raquel Rabionet Janssen, 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 SW, Schmidt U, Schork NJ, Schosser A, Seitz J, Slachtova L, Slagboom PE, Slof-Op 't Landt MCT, Slopien A, Sorbi S, Swiatkowska B, Szatkiewicz JP, Tachmazidou I, Tenconi E, Tortorella A, Tozzi F, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, Tziouvas K, van Elburg AA, van Furth EF, Wagner G, Walton E, Widen E, Zeggini E, Zerwas S, Zipfel S, Bergen AW, Boden JM, Brandt H, Crawford S, Halmi KA, Horwood LJ, Johnson C, Kaplan AS, Kaye WH, Mitchell JE, Olsen CM, Pearson JF, Pedersen NL, Strober M, Werge T, Whiteman DC, Woodside DB, Stuber GD, Gordon S, Grove J, Henders AK, Juréus A, Kirk KM, Larsen JT, Parker R, Petersen L, Jordan J, Kennedy M, Montgomery GW, Wade TD, Birgegård A, Lichtenstein P, Norring C, Landén M, Martin NG, Mortensen PB, Sullivan PF, Breen G, and Bulik CM

Subjects
mental disorders
Abstract

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness 1 , affecting 0.9-4% of women and 0.3% of men 2-4 , with twin-based heritability estimates of 50-60% 5 . Mortality rates are higher than those in other psychiatric disorders 6 , and outcomes are unacceptably poor 7 . Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI) 8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

Published
2019

38. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Author

Watson, H.J. Yilmaz, Z. Thornton, L.M. Hübel, C. Coleman, J.R.I. Gaspar, H.A. Bryois, J. Hinney, A. Leppä, V.M. Mattheisen, M. Medland, S.E. Ripke, S. Yao, S. Giusti-Rodríguez, P. Hanscombe, K.B. Purves, K.L. Adan, R.A.H. Alfredsson, L. Ando, T. Andreassen, O.A. Baker, J.H. Berrettini, W.H. Boehm, I. Boni, C. Perica, V.B. 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. Mayora, M.G. 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. Kaprio, J. Karhunen, L. Karwautz, A. Kas, M.J.H. Kennedy, J.L. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Klareskog, L. 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. Munn-Chernoff, M.A. 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.E. Olsen, C.M. Pearson, J.F. Pedersen, N.L. Strober, M. Werge, T. Whiteman, D.C. Woodside, D.B. Stuber, G.D. Gordon, S. Grove, J. Henders, A.K. Juréus, A. Kirk, K.M. Larsen, J.T. Parker, R. Petersen, L. Jordan, J. Kennedy, M. Montgomery, G.W. Wade, T.D. Birgegård, A. Lichtenstein, P. Norring, C. Landén, M. Martin, N.G. Mortensen, P.B. Sullivan, P.F. Breen, G. Bulik, C.M. Anorexia Nervosa Genetics Initiative Eating Disorders Working Group of the Psychiatric Genomics Consortium

Subjects
mental disorders
Abstract

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9–4% of women and 0.3% of men2–4, with twin-based heritability estimates of 50–60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Published
2019

41. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa

Author

Watson, H.J. Yilmaz, Z. Thornton, L.M. Hübel, C. Coleman, J.R.I. Gaspar, H.A. Bryois, J. Hinney, A. Leppä, V.M. Mattheisen, M. Medland, S.E. Ripke, S. Yao, S. Giusti-Rodríguez, P. Hanscombe, K.B. Purves, K.L. Adan, R.A.H. Alfredsson, L. Ando, T. Andreassen, O.A. Baker, J.H. Berrettini, W.H. Boehm, I. Boni, C. Perica, V.B. 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. Mayora, M.G. 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. Kaprio, J. Karhunen, L. Karwautz, A. Kas, M.J.H. Kennedy, J.L. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Klareskog, L. 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. Munn-Chernoff, M.A. 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 and Watson, H.J. Yilmaz, Z. Thornton, L.M. Hübel, C. Coleman, J.R.I. Gaspar, H.A. Bryois, J. Hinney, A. Leppä, V.M. Mattheisen, M. Medland, S.E. Ripke, S. Yao, S. Giusti-Rodríguez, P. Hanscombe, K.B. Purves, K.L. Adan, R.A.H. Alfredsson, L. Ando, T. Andreassen, O.A. Baker, J.H. Berrettini, W.H. Boehm, I. Boni, C. Perica, V.B. 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. Mayora, M.G. 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. Kaprio, J. Karhunen, L. Karwautz, A. Kas, M.J.H. Kennedy, J.L. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Klareskog, L. 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. Munn-Chernoff, M.A. 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

Abstract

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9–4% of women and 0.3% of men2–4, with twin-based heritability estimates of 50–60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Published
2019

45. Correction to: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa (Molecular Psychiatry, (2018), 23, 5, (1169-1180), 10.1038/mp.2017.88)

Author

Huckins, L.M. Hatzikotoulas, K. Southam, L. Thornton, L.M. Steinberg, J. Aguilera-McKay, F. Treasure, J. Schmidt, U. Gunasinghe, C. Romero, A. Curtis, C. Rhodes, D. Moens, J. Kalsi, G. Dempster, D. Leung, R. Keohane, A. Burghardt, R. Ehrlich, S. Hebebrand, J. Hinney, A. Ludolph, A. Walton, E. Deloukas, P. Hofman, A. Palotie, A. Palta, P. van Rooij, F.J.A. Stirrups, K. Adan, R. Boni, C. Cone, R. Dedoussis, G. van Furth, E. Gonidakis, F. Gorwood, P. Hudson, J. Kaprio, J. Kas, M. Keski-Rahonen, A. Kiezebrink, K. Knudsen, G.-P. Maj, M. Monteleone, A.M. Monteleone, P. Raevuori, A.H. Reichborn-Kjennerud, T. Tozzi, F. Tsitsika, A. van Elburg, A. Collier, D.A. Sullivan, P.F. Breen, G. Bulik, C.M. Zeggini, E. MCT Slof-Op 't Landt Eating Disorder Working Group of the Psychiatric Genomics Consortium

Subjects
GeneralLiterature_INTRODUCTORYANDSURVEY
Abstract

The fortieth author’s name was listed incorrectly. The correct presentation is A Keski-Rahkonen. © 2018, Springer Nature Limited.

Published
2018

48. Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Author

Huckins, L.M. (L. M.), Hatzikotoulas, K. (K.), Southam, L. (Lorraine), Thornton, L.M. (L. M.), Steinberg, J. (J.), Aguilera-McKay, F. (F.), Treasure, J. (J.), Schmidt, U. (U.), Gunasinghe, C. (C.), Romero, A. (A.), Curtis, C. (C.), Rhodes, D. (D.), Moens, J. (J.), Kalsi, G. (G.), Dempster, D. (D.), Leung, R. (R.), Keohane, A. (A.), Burghardt, R. (R.), Ehrlich, S.M. (Stefan), Hebebrand, J. (Johannes), Hinney, A. (Anke), Ludolph, A.C. (Albert), Walton, E. (Esther), Deloukas, P. (Panagiotis), Hofman, A. (Albert), Palotie, A. (Aarno), Palta, P. (Priit), Rooij, F.J.A. (Frank) van, Stirrups, K. (Kathy), Adan, R.A.H. (Roger), Boni, C. (C.), Cone, R. (R.), Dedoussis, G.V. (George), Furth, E.F. (Eric) van, Gonidakis, F. (F.), Gorwood, P. (P.), Hudson, J. (J.), Kaprio, J. (J.), Kas, M.J.H. (Martien), Keski-Rahonen, A. (A.), Kiezebrink, K. (K.), Knudsen, G.-P. (G-P), Maj, M. (M.), Monteleone, A.M. (Alessio Maria), Monteleone, P. (P.), Raevuori, A.H. (A. H.), Reichborn-Kjennerud, T. (T.), Tozzi, F. (F.), Tsitsika, A. (Artemis), Elburg, A.A. (Annemarie) van, Collier, D.A. (David), Sullivan, P.F. (Patrick), Breen, G. (Gerome), Bulik, C.M. (C. M.), Zeggini, E. (E.), Huckins, L.M. (L. M.), Hatzikotoulas, K. (K.), Southam, L. (Lorraine), Thornton, L.M. (L. M.), Steinberg, J. (J.), Aguilera-McKay, F. (F.), Treasure, J. (J.), Schmidt, U. (U.), Gunasinghe, C. (C.), Romero, A. (A.), Curtis, C. (C.), Rhodes, D. (D.), Moens, J. (J.), Kalsi, G. (G.), Dempster, D. (D.), Leung, R. (R.), Keohane, A. (A.), Burghardt, R. (R.), Ehrlich, S.M. (Stefan), Hebebrand, J. (Johannes), Hinney, A. (Anke), Ludolph, A.C. (Albert), Walton, E. (Esther), Deloukas, P. (Panagiotis), Hofman, A. (Albert), Palotie, A. (Aarno), Palta, P. (Priit), Rooij, F.J.A. (Frank) van, Stirrups, K. (Kathy), Adan, R.A.H. (Roger), Boni, C. (C.), Cone, R. (R.), Dedoussis, G.V. (George), Furth, E.F. (Eric) van, Gonidakis, F. (F.), Gorwood, P. (P.), Hudson, J. (J.), Kaprio, J. (J.), Kas, M.J.H. (Martien), Keski-Rahonen, A. (A.), Kiezebrink, K. (K.), Knudsen, G.-P. (G-P), Maj, M. (M.), Monteleone, A.M. (Alessio Maria), Monteleone, P. (P.), Raevuori, A.H. (A. H.), Reichborn-Kjennerud, T. (T.), Tozzi, F. (F.), Tsitsika, A. (Artemis), Elburg, A.A. (Annemarie) van, Collier, D.A. (David), Sullivan, P.F. (Patrick), Breen, G. (Gerome), Bulik, C.M. (C. M.), and Zeggini, E. (E.)

Abstract

The fortieth author's name was listed incorrectly. The correct presentation is A Keski-Rahkonen.

Published
2018
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49. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Author

Huckins, L.M. (L. M.), Hatzikotoulas, K. (K.), Southam, L. (Lorraine), Thornton, L.M. (L. M.), Steinberg, J. (J.), Aguilera-Mckay, F. (F.), Treasure, J. (J.), Schmidt, U. (U.), Gunasinghe, C. (C.), Romero, A. (Atocha), Curtis, C. (C.), Rhodes, D. (D.), Moens, J. (J.), Kalsi, G. (G.), Dempster, D. (D.), Leung, R. (R.), Keohane, A. (A.), Burghardt, R. (R.), Ehrlich, S.M. (Stefan), Hebebrand, J. (Johannes), Hinney, A. (Anke), Ludolph, A.C. (Albert), Walton, E. (Esther), Deloukas, P. (P.), Hofman, A. (A.), Palotie, A. (A.), Palta, P. (Priit), Rooij, F.J.A. (Frank) van, Stirrups, K. (Kathy), Adan, R. (R.), Boni, C. (C.), Cone, R. (R.), Dedoussis, G.V. (George), Furth, E.F. (Eric) van, Gonidakis, F. (F.), Gorwood, P. (P.), Hudson, J. (J.), Kaprio, J. (J.), Kas, M.J.H. (Martien), Keski-Rahonen, A. (A.), Kiezebrink, K. (K.), Knudsen, G.-P. (G. P.), Slof-Op 'T Landt, M.C.T. (M. C.T.), Maj, M. (M.), Monteleone, A.M. (Alessio Maria), Monteleone, P. (P.), Raevuori, A.H. (A. H.), Reichborn-Kjennerud, T. (T.), Tozzi, F. (F.), Tsitsika, A. (A.), Elburg, A.A. (Annemarie) van, Collier, D.A. (David), Sullivan, P.F. (Patrick), Breen, G. (Gerome), Bulik, C.M. (C. M.), Zeggini, E. (E.), Huckins, L.M. (L. M.), Hatzikotoulas, K. (K.), Southam, L. (Lorraine), Thornton, L.M. (L. M.), Steinberg, J. (J.), Aguilera-Mckay, F. (F.), Treasure, J. (J.), Schmidt, U. (U.), Gunasinghe, C. (C.), Romero, A. (Atocha), Curtis, C. (C.), Rhodes, D. (D.), Moens, J. (J.), Kalsi, G. (G.), Dempster, D. (D.), Leung, R. (R.), Keohane, A. (A.), Burghardt, R. (R.), Ehrlich, S.M. (Stefan), Hebebrand, J. (Johannes), Hinney, A. (Anke), Ludolph, A.C. (Albert), Walton, E. (Esther), Deloukas, P. (P.), Hofman, A. (A.), Palotie, A. (A.), Palta, P. (Priit), Rooij, F.J.A. (Frank) van, Stirrups, K. (Kathy), Adan, R. (R.), Boni, C. (C.), Cone, R. (R.), Dedoussis, G.V. (George), Furth, E.F. (Eric) van, Gonidakis, F. (F.), Gorwood, P. (P.), Hudson, J. (J.), Kaprio, J. (J.), Kas, M.J.H. (Martien), Keski-Rahonen, A. (A.), Kiezebrink, K. (K.), Knudsen, G.-P. (G. P.), Slof-Op 'T Landt, M.C.T. (M. C.T.), Maj, M. (M.), Monteleone, A.M. (Alessio Maria), Monteleone, P. (P.), Raevuori, A.H. (A. H.), Reichborn-Kjennerud, T. (T.), Tozzi, F. (F.), Tsitsika, A. (A.), Elburg, A.A. (Annemarie) van, Collier, D.A. (David), Sullivan, P.F. (Patrick), Breen, G. (Gerome), Bulik, C.M. (C. M.), and Zeggini, E. (E.)

Abstract

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10 -6), and rs7700147, an intergenic variant (P=2.93 × 10 -5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Published
2018
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50. Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Author

TN groep Adan, Circulatory Health, Brain, Huckins, L M, Hatzikotoulas, K, Southam, L, Thornton, L M, Steinberg, J, Aguilera-McKay, F, Treasure, J, Schmidt, U, Gunasinghe, C, Romero, A, Curtis, C, Rhodes, D, Moens, J, Kalsi, G, Dempster, D, Leung, R, Keohane, A, Burghardt, R, Ehrlich, S, Hebebrand, J, Hinney, A, Ludolph, A, Walton, E, Deloukas, P, Hofman, A, Palotie, A, Palta, P, van Rooij, F J A, Stirrups, K, Adan, R, Boni, C, Cone, R, Dedoussis, G, van Furth, E, Gonidakis, F, Gorwood, P, Hudson, J, Kaprio, J, Kas, M, Keski-Rahonen, A, Kiezebrink, K, Knudsen, G-P, Maj, M, Monteleone, A M, Monteleone, P, Raevuori, A H, Reichborn-Kjennerud, T, Tozzi, F, Tsitsika, A, van Elburg, A, MCT Slof-Op ’t Landt, TN groep Adan, Circulatory Health, Brain, Huckins, L M, Hatzikotoulas, K, Southam, L, Thornton, L M, Steinberg, J, Aguilera-McKay, F, Treasure, J, Schmidt, U, Gunasinghe, C, Romero, A, Curtis, C, Rhodes, D, Moens, J, Kalsi, G, Dempster, D, Leung, R, Keohane, A, Burghardt, R, Ehrlich, S, Hebebrand, J, Hinney, A, Ludolph, A, Walton, E, Deloukas, P, Hofman, A, Palotie, A, Palta, P, van Rooij, F J A, Stirrups, K, Adan, R, Boni, C, Cone, R, Dedoussis, G, van Furth, E, Gonidakis, F, Gorwood, P, Hudson, J, Kaprio, J, Kas, M, Keski-Rahonen, A, Kiezebrink, K, Knudsen, G-P, Maj, M, Monteleone, A M, Monteleone, P, Raevuori, A H, Reichborn-Kjennerud, T, Tozzi, F, Tsitsika, A, van Elburg, A, and MCT Slof-Op ’t Landt

Published
2018

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