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3. Couleur et soins dans les médecines anciennes aux époques antique et médiévale entre Orient et Occident

Author

Laurence, Moulinier, Boehm, I., Histoire, Archéologie et Littératures des mondes chrétiens et musulmans médiévaux (CIHAM), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-École des hautes études en sciences sociales (EHESS)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), Histoire et Sources des Mondes antiques (HiSoMA), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), CIHAMHisoMa, Isabelle Boehm, Laurence Moulinier-Brogi, Isabelle Boehm, Laurence Moulinier-Brogi, and Christian Rico

Subjects
Pharmacopées traditionnelles, Médecine - Histoire, Médecine ancienne, Couleur -- Terminologie, [SHS.HIST]Humanities and Social Sciences/History, Médecine médiévale -- Histoire -- Sources, [SHS]Humanities and Social Sciences
Abstract

International audience; La couleur de la maladie et la couleur du remède font partie des critères fondamentaux de diagnostic et de thérapeutique dans l’histoire de la médecine et de la pharmacologie. Les contributions réunies ici sont issues d’un colloque consacré à l’utilisation des couleurs au service du soin, aux époques antique et médiévale, et dans une perspective comparatiste, où ont été associées des traditions médicales au-delà de l’Europe, comme le Proche-Orient ou l’Égypte.

Published
2021

9. 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

10. Old Norse -yn (Proto-Germanic *-unjō-) and the Re-Analysis and Spread of Derivational Morphology through Semantic Association. On Old Norse Fjǫrgyn ‘Earth(-goddess)’ and Hlóðyn ‘id.’, Celtic Hercynia (silua) ‘Hercynian forest’, Vedic Pŕ̥śni- ‘mother of the Maruts’, and Proto-Indo-European *perḱ- ‘colourful, spotted, dark’

Author

Blanc, A, Boehm, I, Ginevra, Riccardo, Ginevra (ORCID:0000-0002-6731-6494), Blanc, A, Boehm, I, Ginevra, Riccardo, and Ginevra (ORCID:0000-0002-6731-6494)

Abstract

Nell'articolo sono discusse nuove analisi formali e interpretazioni semantiche per due nomi norreni della dea della Terra, Fjǫrgyn e Hlóðyn, i quali forniscono ulteriori prove del fatto che il suffisso proto-germanico *‐u‐njō‐ (norreno ‐yn) sia stato creato per re‐analisi da un suffisso presente in formazioni protoindoeuropee devī́‐ e che la sua diffusione all'interno del germanico sia da collegarsi a processi analogici innescati da associazioni semantiche. Fjǫrgyn è ricondotto a un derivato ereditato della radice *perḱ‐ 'essere colorato, maculato, scuro' (corrispondente alla diffusa collocazione [terra – scura]) con paralleli in germanico, indo-iranico e, possibilmente, celtico, mentre Hlóðyn viene analizzato come il risultato di una formazione analogica di origine più recente, la quale riflette però l'antichissima concezione della Terra come “portatrice” del cosmo., The paper discusses new formal analyses and semantic interpretations for two Old Norse names of the Earth‐goddess, Fjǫrgyn and Hlóðyn, providing further evidence that the Proto‐Germanic suffix *‐u‐njō‐ (Old Norse ‐yn) was created by re‐analysis from a suffix occurring in Proto‐Indo‐European devī́‐ formations and that its spread within Germanic may have been connected with analogical processes triggered by semantic association. Fjǫrgyn is thus traced back to an inherited derivative of the root *perḱ‐ ‘to be colourful, spotted, dark’ (matching the widespread collocation [dark – earth]) with parallels in Germanic, Indo‐Iranian and, possibly, Celtic, whereas Hlóðyn is analyzed as the outcome of an analogical formation of more recent origin, reflecting, however, the very ancient conception of the Earth as the “bearer” of the cosmos., Cet article traite de deux explications morphologiques et sémantiques nouvelles pour deux noms de la déesse de la terre en vieil islandais, Fjǫrgyn et Hlóðyn. Il montre avec de nouveaux arguments que le suffixe proto‐germanique *‐u‐njō‐ (vieil islandais ‐yn) a été constitué par réanalyse à partir d'un suffixe qui apparaissait dans les formations proto‐indo‐européennes du type de devī́‐ et que sa diffusion à l’intérieur du germanique a dû être liée à des développements analogiques apparus à l’occasion d’associations sémantiques. Ainsi, on rapporte Fjǫrgyn à un dérivé hérité reposant sur la racine *perḱ‐ « être coloré, être tacheté, être sombre », correspondant à la collocation largement répandue [sombre – terre], avec des parallèles en germanique, en indo‐iranien et possiblement en celtique, tandis que Hlóðyn est expliqué comme l’aboutissement d’une formation analogique d’origine plus récente qui reflète tout de même la conception très ancienne de la terre comme la « porteuse » de l’univers.

Published
2021

11. 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

15. 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

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

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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

21. 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

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

22. 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

23. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes

Author

Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR, Josse RG, Califf RM, Goldstein BJ, Shapiro DR, Silverman R, Bethel A, Green J, Hayden S, Hannan K, Quintero K, Rorick T, Berdan L, Leloudis D, Califf S, Wilson M, McFarron D, Trollinger K, Pesarchick J, Eskenazi L, Campbell C, Townes O, Tolsma D, Keenan J, Milton J, Athwal R, Darbyshire J, Doran Z, Kennedy I, Gregory V, Lokhnygina Y, Prather K, Wolfley A, Usman M, Tajjar A, Gray R, Pfeffer MA, Gerstein HC, Groop L, McMurray JJ, Pocock SJ, Clayton T, Sinay I, Brieger D, Stranks S, Scheen A, Lopes R, Tankova T, Hramiak I, Grado CR, Wenying Y, Ge J, Aschner P, Skrha J, Ambos A, Strandberg T, Travert F, Hanefeld M, Riefflin A, Chan JC, Ofner P, Reddy NK, Christopher J, Mathur A, Arambam P, Mittal S, Manchanda M, Wainstein J, Ambrosio G, Pirags V, Jakuboniene N, Mohamed M, Scott R, White H, Cornel J, Halvorsen S, Tykarski A, Veresiu IA, Dreval AV, Misinkova I, Tai E, Krahulec B, Distiller L, Park Y, Rovira A, Alversson M, Chuang LM, Delibasi T, Adler A, Rodbard HW, Marre M, Goff D, Chacra A, DeVore A, Beaven A, Shah B, Hirsch B, Batch B, Bushnell C, Patel C, Melloni C, Henshaw C, Kong D, Bernecki G, Tillman H, Kang HJ, Hawes J, Strickler J, Piccini J, Wilder J, Alexander K, Mahaffey K, Patel K, Hyland K, Newby K, Jackson L, Cooper L, Armaganijan L, Szczeh L, Koshizaka M, Roe M, Morse M, Guimaraes P, Hess P, Tricoci P, Mehta R, Mathews R, Kociol R, Harrison R, Mentz R, Pokorney S, Leblanc T, Lazzarini V, Eapen Z, Truffa A, Fosbol E, Brito F, Katz M, Bahit M, Santos M, Barros P, Bernardez S, Alvarisqueta AF, Arias P, Cagide AL, Calella PR, Cantero MC, Canella JP, Cipullo MA, de Loredo L, Gelersztein ES, Gorban de Lapertosa SB, Klyver MI, Maffei LE, Maldonado N, Oviedo AI, Piskorz DL, Ridruejo MC, Saavedra SS, Sessa HA, Sinay IR, Sposetti GD, Ulla MR, Vico ML, Waitman JN, Binnekamp M, Carroll P, Cheung W, Colman P, Davis T, De Looze F, dEmden M, Fulcher G, Gerstman M, Hamilton A, Lehman S, Moses R, Proietto J, Roberts A, Shaw J, Simpson R, Sinha A, Tan Y, Topliss D, Vora P, Waites J, Crenier L, Descamps O, Keymeulen B, Mathieu C, Nobels F, Van den Bruel A, Van Gaal L, Borges JL, Costa e Forti A, Eliaschewitz FG, Felício JS, Griz LH, Hissa MN, Leite S, Panarotto D, Pimentel Filho P, Rassi N, Saraiva JK, Sgarbi JA, Silva RP, Tambascia M, Weber Silva DM, Bobeva R, Bostandzhieva R, Cinlikov I, Georgieva M, Iliev D, Ilieva E, Kovacheva S, Liubenova L, Nikitov Z, SHeinikova G, Slavcheva A, Spasova V, Temelkova-Kurktschiev T, Velichka D, Yakov A, Carpentier A, Chiasson JL, Constance C, Dumas R, Filteau P, Garceau C, Huynh T, Kaiser S, Kornder J, Leiter L, Mereu L, Miller D, Pandey S, Punthakee Z, Rabasa-Lhoret R, Robitaille Y, Saunders K, Sigal R, Sigalas J, Vizel S, Weisnagel S, Woo V, Yale JF, Yared K, Zinman B, Bunster Balocchi LB, Escobar Cerda 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Bostandzhieva R, Cinlikov I, Georgieva M, Iliev D, Ilieva E, Kovacheva S, Liubenova L, Nikitov Z, SHeinikova G, Slavcheva A, Spasova V, Tankova T, Temelkova-Kurktschiev T, Velichka D, Yakov A, Carpentier A, Chiasson JL, Constance C, Dumas R, Filteau P, Garceau C, Hramiak I, Huynh T, Kaiser S, Kornder J, Leiter L, Mereu L, Miller D, Pandey S, Punthakee Z, Rabasa-Lhoret R, Robitaille Y, Saunders K, Sigal R, Sigalas J, Vizel S, Weisnagel S, Woo V, Yale JF, Yared K, Zinman B, Bunster Balocchi LB, Escobar Cerda EE, Garces Flores EE, Lanas Zanetti FT, Larrazabal Miranda Adel P, Morales Alvarado JM, Olivares Cañon CM, Potthoff Cárdenas SH, Raffo Grado CA, Rodriguez Venegas ME, Saavedra Gajardo VA, Westerberg Maldonado BH, Chen LL, Dong J, Guo X, Li QM, Shi B, Tang XL, Yang T, Yang WY, Zheng SX, Aschner Montoya P, Botero Lopez R, Coronel Arroyo JA, Cure CA, Gómez Medina AM, Molina DI, Perez Amador GA, Reyes Rincon A, Urina Triana MA, Valenzuela Rincon A, Vélez Pelaez S, Yupanqui Lozno H, Brabec T, Brychta T, Hasalova Zapletalova J, Havelkova J, Hejnicova K, Hola O, Hornackova M, Hrdina T, Kafkova D, Kellnerova I, Krystl T, Kutejova V, Mikulkova I, Nevrla J, Pantlikova C, Petr M, Racicka E, Sarbochova R, Skrha J, Smolenakova K, Turcinek R, Urbancova K, Vejvodova J, Vondrakova M, Zachoval R, Alt I, Ambos A, Kaasik Ü, Kiiroja K, Lanno R, Märtsin K, Past M, Vides H, Viitas L, Kantola I, Nieminen S, Perhonen M, Strand J, Strandberg T, Valle T, Clergeot A, Couffinhal T, Courreges JP, Gouet D, Moulin P, Travert F, Ziegler O, Badenhoop K, Behnke T, Bender G, Braun M, Dshabrailov J, Hamann A, Hanefeld M, Himpel-Boenninghoff A, Kamke W, Kasperk C, Luedemann J, Mayr P, Merkel M, Oerter EM, Ohlow MA, Ott P, Overhoff U, Paschen B, Remppis R, Riefflin A, Rose L, Schumm-Draeger PM, Segiet T, Strotmann HJ, Stuchlik G, Stürmer W, Thinesse-Mallwitz M, Tytko A, Wendisch U, Wurziger J, Ho AY, Kam G, Kong AP, Lam YY, Lau EY, Lee S, Siu SC, Tomlinson B, Tsang CC, Yeung VT, Dezső E, Dudás M, Földesi I, Fülöp T, Késmárki N, Koranyi L, Nagy K, Ofner P, Oroszlán T, Pécsvárady Z, Ples Z, Taller A, Agarwal P, Ambulkar S, Aravind S, Balaji V, Christopher J, Kalra S, Kesavadev J, Kudalkar H, Kumar A, Misra A, Mithal A, Mohan V, Pitale S, Ramu M, Reddy N, Shah S, Shamanna P, Sharda A, Sharma A, Shunmugavelu M, Srikanta S, Suryaprakash G, Abramov G, Adawi F, Bashkin A, Darawsha M, Fuchs S, Harman-Boehm I, Hayek T, Jaffe A, Knobler H, Minuchin O, Mosseri M, Shechter M, Shimon I, Stern N, Tsur A, Vishlitzky V, Wainstein J, Alfonsi F, Cavalot F, Del Vecchio L, Frisinghelli A, Gambardella S, Lauro D, Lembo G, Leotta S, Mondillo S, Novo S, Pedrinelli R, Piatti P, Salvioni A, Tritto I, Zavaroni DZ, Ahn KJ, Choi KM, Chung C, Han SJ, Kim DM, Kim IJ, Kim MH, Lee IK, Nam M, Park IeB, Park KS, Park TS, Park Y, Rhee EJ, Yoo SJ, Andersone I, Balode A, Eglite R, Gersamija A, Kakurina N, Jegere B, Leitane I, Pastare S, Pirags V, Stalte V, Teterovska D, Baltramonaitiene K, Barsiene L, Ceponis J, Jakuboniene N, Lasiene J, Levinger A, Sirutaviciene A, Sulskiene M, Urbanaviciene L, Valius L, Varanauskiene E, Velickiene D, Mahendran KA, Abu Hassan MR, Aziz NA, Hussein Z, Ismail IS, Kamaruddin NA, Mohamed M, Nordin Z, Nayar SK, Ramanathan GR, Sothiratnam R, Beijerbacht H, Breedveld R, Cornel JH, Den Hartog F, Hermans W, Kietselaer B, Kooy A, Lenderink T, Nierop P, Remmen J, Rojas Lingan G, Ronner E, Van der Heijden R, Van Hessen M, van Kempen W, Voors-Pette C, Westendorp I, Baker J, Benatar J, Cutfield R, Krebs J, Leikis R, Lunt H, Manning P, Scott R, Williams M, Birkeland K, Claudi T, Halvorsen S, Istad H, Karlsson T, Ossum Gronert J, Arciszewska M, Artemiuk E, Blach E, Blicharski T, Cypryk K, Dabrowska M, Górny G, Górska M, Jakubowska I, Jazwinska-Tarnawska E, Karczmarczyk A, Kitowska-Koterla J, Koltowski L, Krzyzagorska E, Pasternak D, Pentela-Nowicka J, Piesiewicz W, Przekwas-Jaruchowska M, Rajzer M, Salamon-Ferenc A, Sawicki A, Skowron T, Śmiałowski A, Tykarski A, Albota A, Alexandru C, Crisan C, Dumitrescu A, Ferariu IE, Lupusoru DA, Munteanu M, Negru D, Nicolau A, Pintiliei E, Popescu A, Serban G, Veresiu IA, Voitec M, Babenko A, Barbarash O, Bondar I, Chizhov P, Demin A, Dora S, Dreval A, Ershova O, Gratsiansky N, Ketova G, Kotelnikov M, Levashov S, Morugova T, Mustafina S, Pekarskiy S, Raskina T, Rechkova E, Samoylova Y, Sazonova O, Sherenkov A, Shilkina N, Stetsyuk O, Tretyakova T, Turova E, Valeeva F, Zadionchenko V, Dalan R, Tan RS, Tay L, Buganova I, Fabry J, Jan C, Krahulec B, Toserova E, Zak R, Zimanova J, Badat A, Bester F, Burgess L, De Jong D, Distiller L, Ellis G, Fouche L, Govender P, Govind U, Naidoo V, Nieuwoudt G, Nortje H, Rheeder P, Robertson L, Siddique N, Stapelberg AM, Trinder Y, Van Der Merwe A, Van Zyl L, Viljoen M, Wilhase A, Botella M, Civeira Murillo F, de Teresa L, Del Cañizo FJ, Extremera BG, Gimeno EJ, Martin-Hidalgo A, Morales C, Nubiola A, Rovira A, Tinahones Madueño F, Tranche S, Trescolí Serrano C, Alvarsson M, Eizyk E, Gillblad A, Johansson P, Löndahl M, Ohlsson-Önerud Å, Rautio A, Sundström U, Torstensson I, Chen JF, Chou CW, Chuang LM, Ho LT, Hsieh IC, Huang BH, Huang CL, Huang CN, Lai WT, Lo PH, Pei D, Sheu WH, Wang SY, Araz M, Bakiner O, Comlekci A, Delibasi T, Guler S, Sahin I, Sarac F, Tarkun I, Ukinc K, Yilmaz M, Abdulhakim E, Abraham P, Adamson K, Adler A, Blagden M, Bundy C, Daly M, Davies M, Deshpande M, Gillings S, Harvey P, Horvathova V, Horvathova V, Hristova D, Jaap A, Johnson A, Jones H, Kerrane J, Kilvert A, Ko T, Kumar J, Lindsay R, Litchfield J, McCrimmon R, McKnight J, Millward B, Oyesile B, Purewal T, Ravikumar C, Robinson A, Sathyapalan T, Simpson H, Thomas H, Turner W, Weaver J, Wilding J, Wiles P, Adkins K, Akpunonu B, Albu J, Anagnostis G, Anastasi L, Argoud G, Aroda V, Azizad M, Banerji MA, Bartkowiak A Jr, Bays H, Behn P, Bergenstal R, Bhargava A, Bias D, Bolster E, Buchanan P, Busch R, Chadha C, Chang M, Cheng C, Cohen A, Cohen J, Cole B, Connery L, Cooperman M, Cushman W, DAgostino R, Davies M, Dayamani P, De Lemos J, De Meireles M, Dean J, DeHart D, Detweiler R, Donovan D, Dugano-Daphnis P, Dulin M, Dunn F, Eaton C, Erickson B, Estevez R, Feinglos M, Fonseca V, Force R, Forker A, Fox D, Gabriel J, Garcia R, Garvey T, Gaudiani L, Getaneh A, Goff D, Goldberg A, Goldman S, Hairston K, Harris R, Haught W, Hidalgo H Jr, Higgins A, Houchin V, Ison R, Jacobs G, Jaffrani N, Jafry B, Kapsner P, Kaye W, Labroo A, Levinson L, Lewis S, Lillestol M, Luttrell L, Madu I, McNeill R, Merrick B, Metzger F, Nadar V, Nagelberg S, Nash S, Oparil S, Osei K, Papademetriou V, Patel N, Pedley C, Prentiss A, Radbill M, Raisinghani A, Rassouli N, Reddy R, Rees P, Rendell M, Robbins D, Rodbard H, Rohlf J, Roseman H, Rudolph L, Sadler L, Schnall A, Schramm R, Schubart U, Seneviratne T, Shanik M, Snyder H, Sorli C, Stich M, Sweeney ME, Tsao J, Ukwade P, Viswanath D, Vo A, Vogel C, Voyce S, Weintraub H, White J, Wood M, Wu P, Wysham C, Zimmerman R

Subjects
Oral, medicine.medical_specialty, Heart diseases, Glycosylated, Administration, Oral, heart failure, Type 2 diabetes, Dipeptidyl peptidase-4 inhibitor, Kaplan-Meier Estimate, Placebo, Sitagliptin Phosphate, Sitagliptin, Cardiovascular Outcomes, chemistry.chemical_compound, Drug Therapy, Double-Blind Method, Internal medicine, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, Glycated Hemoglobin, Hemoglobin A, Glycosylated, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Follow-Up Studies, Heart Diseases, Heart Failure, Hospitalization, Pyrazines, Triazoles, Medicine (all), business.industry, Semaglutide, Hemoglobin A, General Medicine, ta3121, medicine.disease, Surgery, Cardiovascular diseases, chemistry, Sitagliptin, Administration, Combination, Glycated hemoglobin, business, Type 2, Alogliptin, medicine.drug
Abstract

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to-0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P

Published
2015
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35. Subliminal and supraliminal processing of reward-related stimuli in anorexia nervosa

Author

Boehm, I., King, J. A., Bernardoni, F., Geisler, D., Seidel, M., Ritschel, F., Goschke, T., Haynes, J.-D., Roessner, V., Ehrlich, S., Boehm, I., King, J. A., Bernardoni, F., Geisler, D., Seidel, M., Ritschel, F., Goschke, T., Haynes, J.-D., Roessner, V., and Ehrlich, S.

Abstract

Background. Previous studies have highlighted the role of the brain reward and cognitive control systems in the etiology of anorexia nervosa (AN). In an attempt to disentangle the relative contribution of these systems to the disorder, we used functional magnetic resonance imaging (fMRI) to investigate hemodynamic responses to reward-related stimuli presented both subliminally and supraliminally in acutely underweight AN patients and age-matched healthy controls (HC). Methods. fMRI data were collected from a total of 35 AN patients and 35 HC, while they passively viewed subliminally and supraliminally presented streams of food, positive social, and neutral stimuli. Activation patterns of the group × stimulation condition × stimulus type interaction were interrogated to investigate potential group differences in processing different stimulus types under the two stimulation conditions. Moreover, changes in functional connectivity were investigated using generalized psychophysiological interaction analysis. Results. AN patients showed a generally increased response to supraliminally presented stimuli in the inferior frontal junction (IFJ), but no alterations within the reward system. Increased activation during supraliminal stimulation with food stimuli was observed in the AN group in visual regions including superior occipital gyrus and the fusiform gyrus/parahippocampal gyrus. No group difference was found with respect to the subliminal stimulation condition and functional connectivity. Conclusion. Increased IFJ activation in AN during supraliminal stimulation may indicate hyperactive cognitive control, which resonates with clinical presentation of excessive self-control in AN patients. Increased activation to food stimuli in visual regions may be interpreted in light of an attentional food bias in AN.

Published
2017

36. Serotonin-assoziierte Metaboliten bei jugendlichen Patientinnen mit Anorexia nervosa

Author

Seidel, M, Ritschel, F, Kaiser, S, Boehm, I, Repplinger, S, Geisler, D, King, JA, Bernardoni, F, Henle, T, Roessner, V, and Ehrlich, S

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund: Vorbefunde deuten an, dass eine nahrungsbedingte reduzierte Verfügbarkeit des Präkursors Tryptophan den Serotoningehalt bei Patientinnen mit Anorexia nervosa (AN) senkt. Auch noch im gewichtsrehabilitierten Zustand scheinen Veränderungen des serotonergen Systems eine Rolle[zum vollständigen Text gelangen Sie über die oben angegebene URL], 5. Wissenschaftlicher Kongress der Deutschen Gesellschaft für Essstörungen

Published
2016
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40. Efficacy of CPX-351, (cytarabine: DAunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program

Author

Carol, H, Fan, MMY, Harasym, TO, Boehm, I, Mayer, LD, Houghton, P, Smith, MA, Lock, RB, Carol, H, Fan, MMY, Harasym, TO, Boehm, I, Mayer, LD, Houghton, P, Smith, MA, and Lock, RB

Abstract

Background: CPX-351, a liposomal formulation of cytarabine and daunorubicin co-encapsulated at an optimized synergistic 5:1 molar ratio, has demonstrated improved clinical outcomes over conventional cytarabine/daunorubicin treatment in a randomized phase 2 trial in patients with AML as well as superior efficacy against preclinical leukemia models when compared to the free drugs in combination. Procedures: Given the promising phase 2 data, limited toxicities observed, and the known clinical activities of cytarabine/daunorubicin, we assessed the efficacy of CPX-351 against a panel of childhood ALL xenograft models. Plasma pharmacokinetics of cytarabine and daunorubicin following CPX-351 treatment were determined by HPLC in order to correlate efficacy with drug exposure. Results: CPX-351, at a dose of 5units/kg (corresponding to 5mg/kg cytarabine and 2.2mg/kg daunorubicin), was highly efficacious against all xenografts tested, inducing complete responses in four B-lineage xenografts and partial response in one T-lineage xenograft. These therapeutic responses were achieved with CPX-351 doses that provided drug exposures (based on Cmax and AUC) comparable to those observed in patients with AML. Conclusions: These results suggest that CPX-351 may be a promising chemotherapeutic to be utilized in the treatment of ALL and support its testing in pediatric patients with leukemia.

Published
2015

41. Subliminal and supraliminal processing of reward-related stimuli in anorexia nervosa.

Author

Boehm, I., King, J. A., Bernardoni, F., Geisler, D., Seidel, M., Ritschel, F., Goschke, T., Haynes, J.-D., Roessner, V., and Ehrlich, S.

Subjects
*ANOREXIA nervosa, *CONTROL (Psychology), *AGE distribution, *COGNITION, *EVOKED potentials (Electrophysiology), *FOOD, *HEMODYNAMICS, *LEANNESS, *MAGNETIC resonance imaging, *OCCIPITAL lobe, *PSYCHOPHYSIOLOGY, *REWARD (Psychology), *TEMPORAL lobe, *ATTENTIONAL bias, *DIAGNOSIS
Abstract

BackgroundPrevious studies have highlighted the role of the brain reward and cognitive control systems in the etiology of anorexia nervosa (AN). In an attempt to disentangle the relative contribution of these systems to the disorder, we used functional magnetic resonance imaging (fMRI) to investigate hemodynamic responses to reward-related stimuli presented both subliminally and supraliminally in acutely underweight AN patients and age-matched healthy controls (HC).MethodsfMRI data were collected from a total of 35 AN patients and 35 HC, while they passively viewed subliminally and supraliminally presented streams of food, positive social, and neutral stimuli. Activation patterns of the group×stimulation condition×stimulus type interaction were interrogated to investigate potential group differences in processing different stimulus types under the two stimulation conditions. Moreover, changes in functional connectivity were investigated using generalized psychophysiological interaction analysis.ResultsAN patients showed a generally increased response to supraliminally presented stimuli in the inferior frontal junction (IFJ), but no alterations within the reward system. Increased activation during supraliminal stimulation with food stimuli was observed in the AN group in visual regions including superior occipital gyrus and the fusiform gyrus/parahippocampal gyrus. No group difference was found with respect to the subliminal stimulation condition and functional connectivity.ConclusionIncreased IFJ activation in AN during supraliminal stimulation may indicate hyperactive cognitive control, which resonates with clinical presentation of excessive self-control in AN patients. Increased activation to food stimuli in visual regions may be interpreted in light of an attentional food bias in AN. [ABSTRACT FROM AUTHOR]

Published
2018
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42. Monitoring of Individual Needs in Diabetes (MIND)-2: follow-up data from the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) MIND study

Author

Snoek, F, Kersch, N, Eldrup, E, Harman-Boehm, I, Hermanns, N, Kokoszka, A, Matthews, D, McGuire, B, Pibernik-Okanović, M, Singer, J, de Wit, M, Skovlund, SE, Academic Medical Center, Medical psychology, and EMGO - Lifestyle, overweight and diabetes

Subjects
scale, validity, quality-of-life, randomized controlled-trial, depression, adults, distress, care, diabetes, monitoring patients' well-being, psychological outcomes, metaanalysis
Abstract

OBJECTIVE-To test the effects of implementing computer-assisted Monitoring of Individual Needs in Diabetes (MIND) in routine diabetes care on psychological status and glycemic control, identify predictors of poor psychological outcomes, and evaluate care providers' experiences. RESEARCH DESIGN AND METHODS-The MIND procedure was implemented as part of the annual review in diabetes clinics across eight countries in a prospective observational study with a 1-year follow-up. MIND encompasses well-being (World Health Organization Five Well-Being Index [WHO-5]), diabetes-related distress (Problem Areas in Diabetes [PAID]), a Life Event Inventory, and the patient's agenda for their consultation. Medical data and agreed case- management actions were retrieved from the charts. RESULTS-Of the total 1,567 patients, 891 patients (57%) were monitored at a 1-year follow-up. Twenty-eight percent of the patients screened positive for depression and/or diabetes distress at baseline and considered cases, 17% of whom were receiving psychological care. Cases were significantly more often female and had type 2 diabetes and worse glycemic control compared with noncases. Clinically relevant improvements in WHO-5 and PAID were observed over time in cases, irrespective of referral (effects sizes 0.59 and 0.48, respectively; P < 0.0001). Glycemic control did not change. Female sex, life events, and concomitant chronic diseases were predictors of poor psychological outcomes. MIND was well received by patients and staff. CONCLUSIONS-MIND appears suitable for screening and discussion of emotional distress as part of the annual review. Broader dissemination in diabetes care is recommendable, but sustainability will depend on reimbursement and availability of support services.

Published
2012
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43. Archéosismicité et tsunamis en Méditerranée, approches croisées

Author

Rebe‑marichal, I., Laurenti, A., Boehm, I., Goiran, Jean-Philippe, Histoire et Sources des Mondes antiques (HiSoMA), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), ARCHEORIENT - Environnements et sociétés de l'Orient ancien (Archéorient), Université Lumière - Lyon 2 (UL2)-Centre National de la Recherche Scientifique (CNRS), I. Rebe‑marichal, A. Laurenti, I. Boehm, Jean-Philippe Goiran, École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), and Goiran, Jean-Philippe

Subjects
[SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, [SHS.ENVIR] Humanities and Social Sciences/Environmental studies, Tsunamis, [SHS.GEO] Humanities and Social Sciences/Geography, [SHS.HIST] Humanities and Social Sciences/History, [SHS.ENVIR]Humanities and Social Sciences/Environmental studies, Mediterranée, tsunami, [SHS.GEO]Humanities and Social Sciences/Geography, Mediterranean, [SHS.HIST]Humanities and Social Sciences/History, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2012

45. Espace civil, espace religieux en Grèce mycénienne. Apports et limites d'une approche interdisciplinaire

Author

Müller Celka, Sylvie, Boehm, I., MÜLLER CELKA, Sylvie, ARCHEORIENT - Environnements et sociétés de l'Orient ancien (Archéorient), Université Lumière - Lyon 2 (UL2)-Centre National de la Recherche Scientifique (CNRS), Histoire et Sources des Mondes antiques (HiSoMA), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2010

46. Espace civil, espace religieux en Egée durant la période mycénienne: Approches épigraphique, linguistique et archéologique

Author

Boehm, I., MÜLLER CELKA, Sylvie, Histoire et Sources des Mondes antiques (HiSoMA), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), ARCHEORIENT - Environnements et sociétés de l'Orient ancien (Archéorient), Université Lumière - Lyon 2 (UL2)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), and Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)

Subjects
Mycenaean world, religion mycénienne, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, linéaire A, Linear A, linéaire B, Mycenaen Thebes, mycenaean religion, Akrotiri, Aegean frescoes, fresques égéennes, Thèbes mycéniennes, rituels, rituals, Période mycénienne, Linear B
Abstract

International audience; Y a-t-il une distinction entre civil et religieux en Grèce à l’âge du Bronze ? Les auteurs des contributions réunies dans ce volume abordent cette délicate question en suivant une démarche originale, croiser les points de vue de l'archéologue, de l'épigraphiste et du linguiste. Leur approche innovante de matériaux tels que fresques, archives en linéaire A et linéaire B, espaces construits et non construits, met en évidence les problèmes de définition et fait table rase des idées reçues. Ils montrent comment civil et religieux sont imbriqués dans certaines pratiques collectives assimilables à des rituels et font apparaître ces derniers comme une clé d'interprétation indépendante d’une dichotomie civil/religieux parfois plus réductrice que fructueuse.

Published
2010

47. Espace civil, espace religieux en Egée durant la période mycénienne

Author

Boehm, I., Müller Celka, Sylvie, and MÜLLER CELKA, Sylvie

Subjects
[SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, Mycenaean world, religion mycénienne, linéaire A, Linear A, linéaire B, Mycenaen Thebes, mycenaean religion, Akrotiri, Aegean frescoes, fresques égéennes, Thèbes mycéniennes, rituels, rituals, Période mycénienne, Linear B
Abstract

Y a-t-il une distinction entre civil et religieux en Grèce à l’âge du Bronze ? Les auteurs des contributions réunies dans ce volume abordent cette délicate question en suivant une démarche originale, croiser les points de vue de l'archéologue, de l'épigraphiste et du linguiste. Leur approche innovante de matériaux tels que fresques, archives en linéaire A et linéaire B, espaces construits et non construits, met en évidence les problèmes de définition et fait table rase des idées reçues. Ils montrent comment civil et religieux sont imbriqués dans certaines pratiques collectives assimilables à des rituels et font apparaître ces derniers comme une clé d'interprétation indépendante d’une dichotomie civil/religieux parfois plus réductrice que fructueuse.

Published
2010

48. Cell and molecular determinants of in vivo efficacy of the BH3 mimetic ABT-263 against pediatric acute lymphoblastic leukemia xenografts

Author

Suryani, S, Carol, H, Chonghaile, TN, Frismantas, V, Sarmah, C, High, L, Bornhauser, B, Cowley, MJ, Szymanska, B, Evans, K, Boehm, I, Tonna, E, Jones, L, Manesh, DM, Kurmasheva, RT, Billups, C, Kaplan, W, Letai, A, Bourquin, JP, Houghton, PJ, Smith, MA, Lock, RB, Suryani, S, Carol, H, Chonghaile, TN, Frismantas, V, Sarmah, C, High, L, Bornhauser, B, Cowley, MJ, Szymanska, B, Evans, K, Boehm, I, Tonna, E, Jones, L, Manesh, DM, Kurmasheva, RT, Billups, C, Kaplan, W, Letai, A, Bourquin, JP, Houghton, PJ, Smith, MA, and Lock, RB

Abstract

PURPOSE: Predictive biomarkers are required to identify patients who may benefit from the use of BH3 mimetics such as ABT-263. This study investigated the efficacy of ABT-263 against a panel of patient-derived pediatric acute lymphoblastic leukemia (ALL) xenografts and utilized cell and molecular approaches to identify biomarkers that predict in vivo ABT-263 sensitivity. EXPERIMENTAL DESIGN: The in vivo efficacy of ABT-263 was tested against a panel of 31 patient-derived ALL xenografts composed of MLL-, BCP-, and T-ALL subtypes. Basal gene expression profiles of ALL xenografts were analyzed and confirmed by quantitative RT-PCR, protein expression and BH3 profiling. An in vitro coculture assay with immortalized human mesenchymal cells was utilized to build a predictive model of in vivo ABT-263 sensitivity. RESULTS: ABT-263 demonstrated impressive activity against pediatric ALL xenografts, with 19 of 31 achieving objective responses. Among BCL2 family members, in vivo ABT-263 sensitivity correlated best with low MCL1 mRNA expression levels. BH3 profiling revealed that resistance to ABT-263 correlated with mitochondrial priming by NOXA peptide, suggesting a functional role for MCL1 protein. Using an in vitro coculture assay, a predictive model of in vivo ABT-263 sensitivity was built. Testing this model against 11 xenografts predicted in vivo ABT-263 responses with high sensitivity (50%) and specificity (100%). CONCLUSION: These results highlight the in vivo efficacy of ABT-263 against a broad range of pediatric ALL subtypes and shows that a combination of in vitro functional assays can be used to predict its in vivo efficacy.

Published
2014

49. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study

Author

Pratley, Richard E, Nauck, Michael A, Barnett, A H, Feinglos, M N, Ovalle, F, Harman-Boehm, I, Ye, J, Scott, R, Johnson, S, Stewart, M, Nolan, Christopher, Pratley, Richard E, Nauck, Michael A, Barnett, A H, Feinglos, M N, Ovalle, F, Harman-Boehm, I, Ye, J, Scott, R, Johnson, S, Stewart, M, and Nolan, Christopher

Published
2014

50. Connaissance et diffusion du traité De facultatibus naturalibus à la Renaissance

Author

Boehm, I., Histoire et Sources des Mondes antiques (HiSoMA), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), V. Boudon-Millot, G. Cobolet (éds.), MOM, Bibliothèque, École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Galien, [SHS.CLASS] Humanities and Social Sciences/Classical studies, manuscrit, [SHS.CLASS]Humanities and Social Sciences/Classical studies
Published
2004

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