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Science DOI:10.1126/science.aap8757

Analysis of shared heritability in common disorders of the brain.

Publication TypeJournal Article
Year of Publication2018
AuthorsAnttila, V, Bulik-Sullivan, B, Finucane, HK, Walters, RK, Bras, J, Duncan, L, Escott-Price, V, Falcone, GJ, Gormley, P, Malik, R, Patsopoulos, NA, Ripke, S, Wei, Z, Yu, D, Lee, PH, Turley, P, Grenier-Boley, B, Chouraki, V, Kamatani, Y, Berr, C, Letenneur, L, Hannequin, D, Amouyel, P, Boland, A, Deleuze, J-F, Duron, E, Vardarajan, BN, Reitz, C, Goate, AM, Huentelman, MJ, M Kamboh, I, Larson, EB, Rogaeva, E, St George-Hyslop, P, Hakonarson, H, Kukull, WA, Farrer, LA, Barnes, LL, Beach, TG, F Demirci, Y, Head, E, Hulette, CM, Jicha, GA, Kauwe, JSK, Kaye, JA, Leverenz, JB, Levey, AI, Lieberman, AP, Pankratz, VS, Poon, WW, Quinn, JF, Saykin, AJ, Schneider, LS, Smith, AG, Sonnen, JA, Stern, RA, Van Deerlin, VM, Van Eldik, LJ, Harold, D, Russo, G, Rubinsztein, DC, Bayer, A, Tsolaki, M, Proitsi, P, Fox, NC, Hampel, H, Owen, MJ, Mead, S, Passmore, P, Morgan, K, Nöthen, MM, Rossor, M, Lupton, MK, Hoffmann, P, Kornhuber, J, Lawlor, B, McQuillin, A, Al-Chalabi, A, Bis, JC, Ruiz, A, Boada, M, Seshadri, S, Beiser, A, Rice, K, Van der Lee, SJ, De Jager, PL, Geschwind, DH, Riemenschneider, M, Riedel-Heller, S, Rotter, JI, Ransmayr, G, Hyman, BT, Cruchaga, C, Alegret, M, Winsvold, B, Palta, P, Farh, K-H, Cuenca-León, E, Furlotte, N, Kurth, T, Ligthart, L, Terwindt, GM, Freilinger, T, Ran, C, Gordon, SD, Borck, G, Adams, HHH, Lehtimäki, T, Wedenoja, J, Buring, JE, Schürks, M, Hrafnsdottir, M, Hottenga, J-J, Penninx, B, Artto, V, Kaunisto, M, Vepsäläinen, S, Martin, NG, Montgomery, GW, Kurki, MI, Hämäläinen, E, Huang, H, Huang, J, Sandor, C, Webber, C, Müller-Myhsok, B, Schreiber, S, Salomaa, V, Loehrer, E, Göbel, H, Macaya, A, Pozo-Rosich, P, Hansen, T, Werge, T, Kaprio, J, Metspalu, A, Kubisch, C, Ferrari, MD, Belin, AC, van den Maagdenberg, AMJM, Zwart, J-A, Boomsma, D, Eriksson, N, Olesen, J, Chasman, DI, Nyholt, DR, Avbersek, A, Baum, L, Berkovic, S, Bradfield, J, Buono, R, Catarino, CB, Cossette, P, De Jonghe, P, Depondt, C, Dlugos, D, Ferraro, TN, French, J, Hjalgrim, H, Jamnadas-Khoda, J, Kälviäinen, R, Kunz, WS, Lerche, H, Leu, C, Lindhout, D, Lo, W, Lowenstein, D, McCormack, M, Møller, RS, Molloy, A, Ng, P-W, Oliver, K, Privitera, M, Radtke, R, Ruppert, A-K, Sander, T, Schachter, S, Schankin, C, Scheffer, I, Schoch, S, Sisodiya, SM, Smith, P, Sperling, M, Striano, P, Surges, R, G Thomas, N, Visscher, F, Whelan, CD, Zara, F, Heinzen, EL, Marson, A, Becker, F, Stroink, H, Zimprich, F, Gasser, T, Gibbs, R, Heutink, P, Martinez, M, Morris, HR, Sharma, M, Ryten, M, Mok, KY, Pulit, S, Bevan, S, Holliday, E, Attia, J, Battey, T, Boncoraglio, G, Thijs, V, Chen, W-M, Mitchell, B, Rothwell, P, Sharma, P, Sudlow, C, Vicente, A, Markus, H, Kourkoulis, C, Pera, J, Raffeld, M, Silliman, S, Perica, VBoraska, Thornton, LM, Huckins, LM, William Rayner, N, Lewis, CM, Gratacos, M, Rybakowski, F, Keski-Rahkonen, A, Raevuori, A, Hudson, JI, Reichborn-Kjennerud, T, Monteleone, P, Karwautz, A, Männik, K, Baker, JH, O'Toole, JK, Trace, SE, Davis, OSP, Helder, SG, Ehrlich, S, Herpertz-Dahlmann, B, Danner, UN, van Elburg, AA, Clementi, M, Forzan, M, Docampo, E, Lissowska, J, Hauser, J, Tortorella, A, Maj, M, Gonidakis, F, Tziouvas, K, Papezova, H, Yilmaz, Z, Wagner, G, Cohen-Woods, S, Herms, S, Julià, A, Rabionet, R, Dick, DM, Ripatti, S, Andreassen, OA, Espeseth, T, Lundervold, AJ, Steen, VM, Pinto, D, Scherer, SW, Aschauer, H, Schosser, A, Alfredsson, L, Padyukov, L, Halmi, KA, Mitchell, J, Strober, M, Bergen, AW, Kaye, W, Szatkiewicz, JPeng, Cormand, B, Ramos-Quiroga, JAntoni, Sánchez-Mora, C, Ribasés, M, Casas, M, Hervas, A, Arranz, MJesús, Haavik, J, Zayats, T, Johansson, S, Williams, N, Dempfle, A, Rothenberger, A, Kuntsi, J, Oades, RD, Banaschewski, T, Franke, B, Buitelaar, JK, Vasquez, AArias, Doyle, AE, Reif, A, Lesch, K-P, Freitag, C, Rivero, O, Palmason, H, Romanos, M, Langley, K, Rietschel, M, Witt, SH, Dalsgaard, S, Børglum, AD, Waldman, I, Wilmot, B, Molly, N, Bau, CHD, Crosbie, J, Schachar, R, Loo, SK, McGough, JJ, Grevet, EH, Medland, SE, Robinson, E, Weiss, LA, Bacchelli, E, Bailey, A, Bal, V, Battaglia, A, Betancur, C, Bolton, P, Cantor, R, Celestino-Soper, P, Dawson, G, De Rubeis, S, Duque, F, Green, A, Klauck, SM, Leboyer, M, Levitt, P, Maestrini, E, Mane, S, De-Luca, DMoreno-, Parr, J, Regan, R, Reichenberg, A, Sandin, S, Vorstman, J, Wassink, T, Wijsman, E, Cook, E, Santangelo, S, Delorme, R, Rogé, B, Magalhaes, T, Arking, D, Schulze, TG, Thompson, RC, Strohmaier, J, Matthews, K, Melle, I, Morris, D, Blackwood, D, McIntosh, A, Bergen, SE, Schalling, M, Jamain, S, Maaser, A, Fischer, SB, Reinbold, CS, Fullerton, JM, Guzman-Parra, J, Mayoral, F, Schofield, PR, Cichon, S, Mühleisen, TW, Degenhardt, F, Schumacher, J, Bauer, M, Mitchell, PB, Gershon, ES, Rice, J, Potash, JB, Zandi, PP, Craddock, N, I Ferrier, N, Alda, M, Rouleau, GA, Turecki, G, Ophoff, R, Pato, C, Anjorin, A, Stahl, E, Leber, M, Czerski, PM, Cruceanu, C, Jones, IR, Posthuma, D, Andlauer, TFM, Forstner, AJ, Streit, F, Baune, BT, Air, T, Sinnamon, G, Wray, NR, MacIntyre, DJ, Porteous, D, Homuth, G, Rivera, M, Grove, J, Middeldorp, CM, Hickie, I, Pergadia, M, Mehta, D, Smit, JH, Jansen, R, de Geus, E, Dunn, E, Li, QS, Nauck, M, Schoevers, RA, Beekman, ATf, Knowles, JA, Viktorin, A, Arnold, P, Barr, CL, Bedoya-Berrio, G, O Bienvenu, J, Brentani, H, Burton, C, Camarena, B, Cappi, C, Cath, D, Cavallini, M, Cusi, D, Darrow, S, Denys, D, Derks, EM, Dietrich, A, Fernandez, T, Figee, M, Freimer, N, Gerber, G, Grados, M, Greenberg, E, Hanna, GL, Hartmann, A, Hirschtritt, ME, Hoekstra, PJ, Huang, A, Huyser, C, Illmann, C, Jenike, M, Kuperman, S, Leventhal, B, Lochner, C, Lyon, GJ, Macciardi, F, Madruga-Garrido, M, Malaty, IA, Maras, A, McGrath, L, Miguel, EC, Mir, P, Nestadt, G, Nicolini, H, Okun, MS, Pakstis, A, Paschou, P, Piacentini, J, Pittenger, C, Plessen, K, Ramensky, V, Ramos, EM, Reus, V, Richter, MA, Riddle, MA, Robertson, MM, Roessner, V, Rosário, M, Samuels, JF, Sandor, P, Stein, DJ, Tsetsos, F, Van Nieuwerburgh, F, Weatherall, S, Wendland, JR, Wolanczyk, T, Worbe, Y, Zai, G, Goes, FS, McLaughlin, N, Nestadt, PS, Grabe, H-J, Depienne, C, Konkashbaev, A, Lanzagorta, N, Valencia-Duarte, A, Bramon, E, Buccola, N, Cahn, W, Cairns, M, Chong, SA, Cohen, D, Crespo-Facorro, B, Crowley, J, Davidson, M, DeLisi, L, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Haan, L, Hougaard, D, Karachanak-Yankova, S, Khrunin, A, Klovins, J, Kučinskas, V, Keong, JLee Chee, Limborska, S, Loughland, C, Lönnqvist, J, Maher, B, Mattheisen, M, McDonald, C, Murphy, KC, Nenadic, I, Van Os, J, Pantelis, C, Pato, M, Petryshen, T, Quested, D, Roussos, P, Sanders, AR, Schall, U, Schwab, SG, Sim, K, So, H-C, Stögmann, E, Subramaniam, M, Toncheva, D, Waddington, J, Walters, J, Weiser, M, Cheng, W, Cloninger, R, Curtis, D, Gejman, PV, Henskens, F, Mattingsdal, M, Oh, S-Y, Scott, R, Webb, B, Breen, G, Churchhouse, C, Bulik, CM, Daly, M, Dichgans, M, Faraone, SV, Guerreiro, R, Holmans, P, Kendler, KS, Koeleman, B, Mathews, CA, Price, A, Scharf, J, Sklar, P, Williams, J, Wood, NW, Cotsapas, C, Palotie, A, Smoller, JW, Sullivan, P, Rosand, J, Corvin, A, Neale, BM, Schott, JM, Anney, R, Elia, J, Grigoroiu-Serbanescu, M, Edenberg, HJ, Murray, R
Corporate AuthorsBrainstorm Consortium
JournalScience
Volume360
Issue6395
Date Published2018 06 22
ISSN1095-9203
KeywordsBrain Diseases, Genetic Variation, Genome-Wide Association Study, Humans, Mental Disorders, Phenotype, Quantitative Trait, Heritable, Risk Factors
Abstract

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

DOI10.1126/science.aap8757
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29930110?dopt=Abstract

Alternate JournalScience
PubMed ID29930110
PubMed Central IDPMC6097237
Grant ListR01 NS017950 / NS / NINDS NIH HHS / United States
K01 MH109782 / MH / NIMH NIH HHS / United States
R01 AG058501 / AG / NIA NIH HHS / United States
MR/L501529/1 / / Medical Research Council / United Kingdom
UL1 TR001863 / TR / NCATS NIH HHS / United States
UL1 TR002369 / TR / NCATS NIH HHS / United States
R25 MH077823 / MH / NIMH NIH HHS / United States
U01 AG016976 / AG / NIA NIH HHS / United States
P01 AG003991 / AG / NIA NIH HHS / United States
P50 AG005681 / AG / NIA NIH HHS / United States
P01 AG026276 / AG / NIA NIH HHS / United States
MC_G1000735 / / Medical Research Council / United Kingdom
MR/K026992/1 / / Medical Research Council / United Kingdom
P50 AG005136 / AG / NIA NIH HHS / United States
MR/L501554/1 / / Medical Research Council / United Kingdom
P30 AG008017 / AG / NIA NIH HHS / United States
U01 MH109536 / MH / NIMH NIH HHS / United States
R01 MH106490 / MH / NIMH NIH HHS / United States
G0800637 / / Medical Research Council / United Kingdom
P50 AG005133 / AG / NIA NIH HHS / United States
T32 MH076694 / MH / NIMH NIH HHS / United States
J-0901 / / Parkinson's UK / United Kingdom
R00 MH101367 / MH / NIMH NIH HHS / United States
R01 AG030653 / AG / NIA NIH HHS / United States
R01 MH107649 / MH / NIMH NIH HHS / United States
R01 MH092293 / MH / NIMH NIH HHS / United States
R01 AG041718 / AG / NIA NIH HHS / United States
U01 MH094432 / MH / NIMH NIH HHS / United States
Z99 AG999999 / NULL / Intramural NIH HHS / United States