Genetic architecture of subcortical brain structures in 38,851 individuals.
| Title | Genetic architecture of subcortical brain structures in 38,851 individuals. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Satizabal, CL, Adams, HHH, Hibar, DP, White, CC, Knol, MJ, Stein, JL, Scholz, M, Sargurupremraj, M, Jahanshad, N, Roshchupkin, GV, Smith, AV, Bis, JC, Jian, X, Luciano, M, Hofer, E, Teumer, A, van der Lee, SJ, Yang, J, Yanek, LR, Lee, TV, Li, S, Hu, Y, Koh, JYu, Eicher, JD, Desrivières, S, Arias-Vasquez, A, Chauhan, G, Athanasiu, L, Rentería, ME, Kim, S, Hoehn, D, Armstrong, NJ, Chen, Q, Holmes, AJ, Braber, Aden, Kloszewska, I, Andersson, M, Espeseth, T, Grimm, O, Abramovic, L, Alhusaini, S, Milaneschi, Y, Papmeyer, M, Axelsson, T, Ehrlich, S, Roiz-Santiañez, R, Kraemer, B, Håberg, AK, Jones, HJ, G Pike, B, Stein, DJ, Stevens, A, Bralten, J, Vernooij, MW, Harris, TB, Filippi, I, A Witte, V, Guadalupe, T, Wittfeld, K, Mosley, TH, Becker, JT, Doan, NTrung, Hagenaars, SP, Saba, Y, Cuellar-Partida, G, Amin, N, Hilal, S, Nho, K, Mirza-Schreiber, N, Arfanakis, K, Becker, DM, Ames, D, Goldman, AL, Lee, PH, Boomsma, DI, Lovestone, S, Giddaluru, S, Le Hellard, S, Mattheisen, M, Bohlken, MM, Kasperaviciute, D, Schmaal, L, Lawrie, SM, Agartz, I, Walton, E, Tordesillas-Gutierrez, D, Davies, GE, Shin, J, Ipser, JC, Vinke, LN, Hoogman, M, Jia, T, Burkhardt, R, Klein, M, Crivello, F, Janowitz, D, Carmichael, O, Haukvik, UK, Aribisala, BS, Schmidt, H, Strike, LT, Cheng, C-Y, Risacher, SL, Pütz, B, Fleischman, DA, Assareh, AA, Mattay, VS, Buckner, RL, Mecocci, P, Dale, AM, Cichon, S, Boks, MP, Matarin, M, Penninx, BWJH, Calhoun, VD, M Chakravarty, M, Marquand, AF, Macare, C, Masouleh, SKharabian, Oosterlaan, J, Amouyel, P, Hegenscheid, K, Rotter, JI, Schork, AJ, Liewald, DCM, de Zubicaray, GI, Wong, TYin, Shen, L, Sämann, PG, Brodaty, H, Roffman, JL, de Geus, EJC, Tsolaki, M, Erk, S, van Eijk, KR, Cavalleri, GL, van der Wee, NJA, McIntosh, AM, Gollub, RL, Bulayeva, KB, Bernard, M, Richards, JS, Himali, JJ, Loeffler, M, Rommelse, N, Hoffmann, W, Westlye, LT, Hernández, MCValdés, Hansell, NK, van Erp, TGM, Wolf, C, Kwok, JBJ, Vellas, B, Heinz, A, Loohuis, LMOlde, Delanty, N, Ho, B-C, Ching, CRK, Shumskaya, E, Singh, B, Hofman, A, van der Meer, D, Homuth, G, Psaty, BM, Bastin, ME, Montgomery, GW, Foroud, TM, Reppermund, S, Hottenga, J-J, Simmons, A, Meyer-Lindenberg, A, Cahn, W, Whelan, CD, van Donkelaar, MMJ, Yang, Q, Hosten, N, Green, RC, Thalamuthu, A, Mohnke, S, Pol, HEHulshoff, Lin, H, Jack, CR, Schofield, PR, Mühleisen, TW, Maillard, P, Potkin, SG, Wen, W, Fletcher, E, Toga, AW, Gruber, O, Huentelman, M, Smith, GDavey, Launer, LJ, Nyberg, L, Jönsson, EG, Crespo-Facorro, B, Koen, N, Greve, DN, Uitterlinden, AG, Weinberger, DR, Steen, VM, Fedko, IO, Groenewold, NA, Niessen, WJ, Toro, R, Tzourio, C, Longstreth, WT, M Ikram, K, Smoller, JW, van Tol, M-J, Sussmann, JE, Paus, T, Lemaître, H, Schroeter, ML, Mazoyer, B, Andreassen, OA, Holsboer, F, Depondt, C, Veltman, DJ, Turner, JA, Pausova, Z, Schumann, G, van Rooij, D, Djurovic, S, Deary, IJ, McMahon, KL, Müller-Myhsok, B, Brouwer, RM, Soininen, H, Pandolfo, M, Wassink, TH, Cheung, JW, Wolfers, T, Martinot, J-L, Zwiers, MP, Nauck, M, Melle, I, Martin, NG, Kanai, R, Westman, E, Kahn, RS, Sisodiya, SM, White, T, Saremi, A, van Bokhoven, H, Brunner, HG, Völzke, H, Wright, MJ, Ent, Dvan 't, Nöthen, MM, Ophoff, RA, Buitelaar, JK, Fernández, G, Sachdev, PS, Rietschel, M, van Haren, NEM, Fisher, SE, Beiser, AS, Francks, C, Saykin, AJ, Mather, KA, Romanczuk-Seiferth, N, Hartman, CA, DeStefano, AL, Heslenfeld, DJ, Weiner, MW, Walter, H, Hoekstra, PJ, Nyquist, PA, Franke, B, Bennett, DA, Grabe, HJ, Johnson, AD, Chen, C, van Duijn, CM, Lopez, OL, Fornage, M, Wardlaw, JM, Schmidt, R, DeCarli, C, De Jager, PL, Villringer, A, Debette, S, Gudnason, V, Medland, SE, Shulman, JM, Thompson, PM, Seshadri, S, M Ikram, A |
| Journal | Nat Genet |
| Volume | 51 |
| Issue | 11 |
| Pagination | 1624-1636 |
| Date Published | 2019 11 |
| ISSN | 1546-1718 |
| Keywords | Adult, Aged, Animals, Brain, Cohort Studies, Drosophila melanogaster, Genetic Variation, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Middle Aged, Neurodevelopmental Disorders, Organ Size |
| Abstract | Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease. |
| DOI | 10.1038/s41588-019-0511-y |
| Alternate Journal | Nat Genet |
| PubMed ID | 31636452 |
| PubMed Central ID | PMC7055269 |
| Grant List | UH3 NS100605 / NS / NINDS NIH HHS / United States R01 NS087541 / NS / NINDS NIH HHS / United States U01 HL120393 / HL / NHLBI NIH HHS / United States UL1 TR000153 / TR / NCATS NIH HHS / United States MR/S015132/1 / MRC_ / Medical Research Council / United Kingdom P30 AG010161 / AG / NIA NIH HHS / United States R01AG059874 / / U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) / International R00 MH101367 / MH / NIMH NIH HHS / United States U01 AG052409 / AG / NIA NIH HHS / United States U01 AG049505 / AG / NIA NIH HHS / United States R01 AG054076 / AG / NIA NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States MC_QA137853 / MRC_ / Medical Research Council / United Kingdom U01 HL130114 / HL / NHLBI NIH HHS / United States MR/M013111/1 / MRC_ / Medical Research Council / United Kingdom G1001245 / MRC_ / Medical Research Council / United Kingdom MC_UU_00011/1 / MRC_ / Medical Research Council / United Kingdom R01 AG017917 / AG / NIA NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States R01MH111671 / / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) / International MR/N027558/1 / MRC_ / Medical Research Council / United Kingdom T32 AG058507 / AG / NIA NIH HHS / United States MC_UU_00011/1 / / RCUK | MRC | Medical Research Foundation / International R01MH117601 / / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) / International C06RR029965 / / U.S. Department of Health & Human Services | NIH | National Center for Research Resources (NCRR) / International K99MH116115 / / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) / International P30 AG010129 / AG / NIA NIH HHS / United States MC_PC_17228 / MRC_ / Medical Research Council / United Kingdom BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom K99MH102357 / / U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) / International R03 AG054936 / AG / NIA NIH HHS / United States R01 MH119243 / MH / NIMH NIH HHS / United States R01 AG015819 / AG / NIA NIH HHS / United States |