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Nat Genet DOI:10.1038/ng.3725

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects.

Publication TypeJournal Article
Year of Publication2017
AuthorsMarshall, CR, Howrigan, DP, Merico, D, Thiruvahindrapuram, B, Wu, W, Greer, DS, Antaki, D, Shetty, A, Holmans, PA, Pinto, D, Gujral, M, Brandler, WM, Malhotra, D, Wang, Z, Fajarado, KVFuentes, Maile, MS, Ripke, S, Agartz, I, Albus, M, Alexander, M, Amin, F, Atkins, J, Bacanu, SA, Belliveau, RA, Bergen, SE, Bertalan, M, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Bulik-Sullivan, B, Byerley, W, Cahn, W, Cai, G, Cairns, MJ, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Cheng, W, C Cloninger, R, Cohen, D, Cormican, P, Craddock, N, Crespo-Facorro, B, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, DeLisi, LE, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farh, K-H, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedman, JI, Forstner, AJ, Fromer, M, Genovese, G, Georgieva, L, Gershon, ES, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Gratten, J, De Haan, L, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Huang, H, Ikeda, M, Joa, I, Kähler, AK, Kahn, RS, Kalaydjieva, L, Karjalainen, J, Kavanagh, D, Keller, MC, Kelly, BJ, Kennedy, JL, Kim, Y, Knowles, JA, Konte, B, Laurent, C, Lee, P, S Lee, H, Legge, SE, Lerer, B, Levy, DL, Liang, K-Y, Lieberman, J, Lönnqvist, J, Loughland, CM, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Müller-Myhsok, B, Murphy, KC, Murray, RM, Myin-Germeys, I, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, Oh, S-Y, Olincy, A, Olsen, L, F O'Neill, A, Van Os, J, Pantelis, C, Papadimitriou, GN, Parkhomenko, E, Pato, MT, Paunio, T, Perkins, DO, Pers, TH, Pietilainen, O, Pimm, J, Pocklington, AJ, Powell, J, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Savitz, A, Schall, U, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Silverman, JM, Smoller, JW, Söderman, E, Spencer, CCA, Stahl, EA, Strengman, E, Strohmaier, J, T Stroup, S, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Thirumalai, S, Tooney, PA, Veijola, J, Visscher, PM, Waddington, J, Walsh, D, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wormley, BK, Wray, NR, Wu, JQin, Zai, CC, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Bramon, E, Buxbaum, JD, Cichon, S, Collier, DA, Corvin, A, Daly, MJ, Darvasi, A, Domenici, E, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jönsson, EG, Kendler, KS, Kirov, G, Knight, J, Levinson, DF, Li, QS, McCarroll, SA, McQuillin, A, Moran, JL, Mowry, BJ, Nöthen, MM, Ophoff, RA, Owen, MJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, D, Rietschel, M, Riley, BP, Rujescu, D, Sklar, P, St Clair, D, Walters, JTR, Werge, T, Sullivan, PF, O'Donovan, MC, Scherer, SW, Neale, BM, Sebat, J
Corporate AuthorsPsychosis Endophenotypes International Consortium, CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium
JournalNat Genet
Volume49
Issue1
Pages27-35
Date Published2017 01
ISSN1546-1718
KeywordsCase-Control Studies, DNA Copy Number Variations, Female, Genetic Loci, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Risk Factors, Schizophrenia
Abstract

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.

DOI10.1038/ng.3725
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/27869829?dopt=Abstract

Alternate JournalNat. Genet.
PubMed ID27869829
PubMed Central IDPMC5737772
Grant ListR01 MH095034 / MH / NIMH NIH HHS / United States
MR/K013807/1 / / Medical Research Council / United Kingdom
U01 MH094411 / MH / NIMH NIH HHS / United States
RP-PG-0606-1049 / / Department of Health / United Kingdom
G1100583 / / Medical Research Council / United Kingdom
G0700995 / / Medical Research Council / United Kingdom
MR/K004867/1 / / Medical Research Council / United Kingdom
U01 MH109536 / MH / NIMH NIH HHS / United States
U01 MH109501 / MH / NIMH NIH HHS / United States
U01 MH109514 / MH / NIMH NIH HHS / United States
G0600972 / / Medical Research Council / United Kingdom
G0901310 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom
U01 MH109539 / MH / NIMH NIH HHS / United States
U01 MH094421 / MH / NIMH NIH HHS / United States
PDA/02/06/016 / / Department of Health / United Kingdom
U01 MH109528 / MH / NIMH NIH HHS / United States