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The CHRM3 gene is implicated in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia

Published online by Cambridge University Press:  09 March 2016


Q. Wang
Affiliation:
Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China State Key Laboratory of Biotherapy, Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
W. Cheng
Affiliation:
Centre for Computational Systems Biology, Fudan University, Shanghai, People's Republic of China
M. Li
Affiliation:
State Key Laboratory of Brain and Cognitive Sciences, Centre for Genomic Sciences and Department of Psychiatry, University of Hong Kong, Pokfulam, S.A.R. China
H. Ren
Affiliation:
Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
X. Hu
Affiliation:
Biobank, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
W. Deng
Affiliation:
Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
M. Li
Affiliation:
Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
X. Ma
Affiliation:
State Key Laboratory of Biotherapy, Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
L. Zhao
Affiliation:
State Key Laboratory of Biotherapy, Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
Y. Wang
Affiliation:
State Key Laboratory of Biotherapy, Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
B. Xiang
Affiliation:
Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
H.-M. Wu
Affiliation:
State Key Laboratory of Brain and Cognitive Sciences, Centre for Genomic Sciences and Department of Psychiatry, University of Hong Kong, Pokfulam, S.A.R. China
P. C. Sham
Affiliation:
State Key Laboratory of Brain and Cognitive Sciences, Centre for Genomic Sciences and Department of Psychiatry, University of Hong Kong, Pokfulam, S.A.R. China
J. Feng
Affiliation:
Centre for Computational Systems Biology, Fudan University, Shanghai, People's Republic of China
T. Li
Affiliation:
Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China State Key Laboratory of Biotherapy, Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
Corresponding
E-mail address:

Abstract

Background

The genetic influences in human brain structure and function and impaired functional connectivities are the hallmarks of the schizophrenic brain. To explore how common genetic variants affect the connectivities in schizophrenia, we applied genome-wide association studies assaying the abnormal neural connectivities in schizophrenia as quantitative traits.

Method

We recruited 161 first-onset and treatment-naive patients with schizophrenia and 150 healthy controls. All the participants underwent scanning with a 3 T-magnetic resonance imaging scanner to acquire structural and functional imaging data and genotyping using the HumanOmniZhongHua-8 BeadChip. The brain-wide association study approach was employed to account for the inherent modular nature of brain connectivities.

Results

We found differences in four abnormal functional connectivities [left rectus to left thalamus (REC.L–THA.L), left rectus to right thalamus (REC.L–THA.R), left superior orbital cortex to left thalamus (ORBsup.L–THA.L) and left superior orbital cortex to right thalamus (ORBsup.L–THA.R)] between the two groups. Univariate single nucleotide polymorphism (SNP)-based association revealed that the SNP rs6800381, located nearest to the CHRM3 (cholinergic receptor, muscarinic 3) gene, reached genomic significance (p = 1.768 × 10−8) using REC.L–THA.R as the phenotype. Multivariate gene-based association revealed that the FAM12A (family with sequence similarity 12, member A) gene nearly reached genomic significance (nominal p = 2.22 × 10–6, corrected p = 0.05).

Conclusions

Overall, we identified the first evidence that the CHRM3 gene plays a role in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia. Identification of these genetic variants using neuroimaging genetics provides insights into the causes of variability in human brain development, and may help us determine the mechanisms of dysfunction in schizophrenia.


Type
Original Articles
Copyright
Copyright © Cambridge University Press 2016 

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References

Andersson, MA, Ek, F, Olsson, R (2015). Using visual lateralization to model learning and memory in zebrafish larvae. Scientific Reports 5, 8667.CrossRefGoogle ScholarPubMed
Andreasen, NC, O'Leary, DS, Cizadlo, T, Arndt, S, Rezai, K, Ponto, LL, Watkins, GL, Hichwa, RD (1996). Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal–thalamic–cerebellar circuitry. Proceedings of the National Academy of Sciences 93, 99859990.CrossRefGoogle ScholarPubMed
Andrews, J, Wang, L, Csernansky, JG, Gado, MH, Barch, DM (2006). Abnormalities of thalamic activation and cognition in schizophrenia. American Journal of Psychiatry 163, 463469.CrossRefGoogle ScholarPubMed
Anticevic, A, Cole, MW, Repovs, G, Murray, JD, Brumbaugh, MS, Winkler, AM, Savic, A, Krystal, JH, Pearlson, GD, Glahn, DC (2014). Characterizing thalamo-cortical disturbances in schizophrenia and bipolar illness. Cerebral Cortex 24, 31163130.CrossRefGoogle ScholarPubMed
Anticevic, A, Hu, X, Xiao, Y, Hu, J, Li, F, Bi, F, Cole, MW, Savic, A, Yang, GJ, Repovs, G, Murray, JD, Wang, XJ, Huang, X, Lui, S, Krystal, JH, Gong, Q (2015). Early-course unmedicated schizophrenia patients exhibit elevated prefrontal connectivity associated with longitudinal change. Journal of Neuroscience 35, 267286.CrossRefGoogle Scholar
Arnedo, J, Svrakic, DM, Del Val, C, Romero-Zaliz, R, Hernández-Cuervo, H; Molecular Genetics of Schizophrenia Consortium, Fanous, AH, Pato, MT, Pato, CN, de Erausquin, GA, Cloninger, CR, Zwir, I (2015). Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies. American Journal of Psychiatry 172, 139153.CrossRefGoogle ScholarPubMed
Aulchenko, YS, Ripke, S, Isaacs, A, van Duijn, CM (2007). GenABEL: an R library for genome-wide association analysis. Bioinformatics 23, 12941296.CrossRefGoogle Scholar
Basson, J, Sung, YJ, Schwander, K, Kume, R, Simino, J, de las Fuentes, L, Rao, D (2014). Gene–education interactions identify novel blood pressure loci in the Framingham Heart Study. American Journal of Hypertension 27, 431444.CrossRefGoogle ScholarPubMed
Blumberg, HP, Stern, E, Ricketts, S, Martinez, D, de Asis, J, White, T, Epstein, J, Isenberg, N, McBride, PA, Kemperman, I, Emmerich, S, Dhawan, V, Eidelberg, D, Kocsis, JH, Silbersweig, DA (1999). Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder. American Journal of Psychiatry 156, 19861988.Google ScholarPubMed
Broyd, SJ, Demanuele, C, Debener, S, Helps, SK, James, CJ, Sonuga-Barke, EJ (2009). Default-mode brain dysfunction in mental disorders: a systematic review. Neuroscience and Biobehavioral Reviews 33, 279296.CrossRefGoogle ScholarPubMed
Byne, W, Buchsbaum, MS, Mattiace, LA, Hazlett, EA, Kemether, E, Elhakem, SL, Purohit, DP, Haroutunian, V, Jones, L (2002). Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia. American Journal of Psychiatry 159, 5965.CrossRefGoogle ScholarPubMed
Celada, P, Llado-Pelfort, L, Santana, N, Kargieman, L, Troyano-Rodriguez, E, Riga, MS, Artigas, F (2013). Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action. International Journal of Neuropsychopharmacology 16, 21452163.CrossRefGoogle ScholarPubMed
Cheng, W, Palaniyappan, L, Li, M, Kendrick, KM, Zhang, J, Luo, Q, Liu, Z, Yu, R, Deng, W, Wang, Q, Ma, X, Guo, W, Francis, S, Liddle, P, Mayer, AR, Schumann, G, Li, T, Feng, J (2015). Voxel-based, brain-wide association study of aberrant functional connectivity in schizophrenia implicates thalamocortical circuitry. npj Schizophrenia 1, 15016.CrossRefGoogle ScholarPubMed
Chun, S, Westmoreland, JJ, Bayazitov, IT, Eddins, D, Pani, AK, Smeyne, RJ, Yu, J, Blundon, JA, Zakharenko, SS (2014). Specific disruption of thalamic inputs to the auditory cortex in schizophrenia models. Science 344, 11781182.CrossRefGoogle ScholarPubMed
Cross-Disorder Group of the Psychiatric Genomics Consortium, Lee, SH, Ripke, S, Neale, BM, Faraone, SV, Purcell, SM, Perlis, RH, Mowry, BJ, Thapar, A, Goddard, ME, Witte, JS, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, OA, Anjorin, A, Anney, R, Anttila, V, Arking, DE, Asherson, P, Azevedo, MH, Backlund, L, Badner, JA, Bailey, AJ, Banaschewski, T, Barchas, JD, Barnes, MR, Barrett, TB, Bass, N, Battaglia, A, Bauer, M, Bayés, M, Bellivier, F, Bergen, SE, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, EB, Black, DW, Blackwood, DH, Bloss, CS, Boehnke, M, Boomsma, DI, Breen, G, Breuer, R, Bruggeman, R, Cormican, P, Buccola, NG, Buitelaar, JK, Bunney, WE, Buxbaum, JD, Byerley, WF, Byrne, EM, Caesar, S, Cahn, W, Cantor, RM, Casas, M, Chakravarti, A, Chambert, K, Choudhury, K, Cichon, S, Cloninger, CR, Collier, DA, Cook, EH, Coon, H, Cormand, B, Corvin, A, Coryell, WH, Craig, DW, Craig, IW, Crosbie, J, Cuccaro, ML, Curtis, D, Czamara, D, Datta, S, Dawson, G, Day, R, De Geus, EJ, Degenhardt, F, Djurovic, S, Donohoe, GJ, Doyle, AE, Duan, J, Dudbridge, F, Duketis, E, Ebstein, RP, Edenberg, HJ, Elia, J, Ennis, S, Etain, B, Fanous, A, Farmer, AE, Ferrier, IN, Flickinger, M, Fombonne, E, Foroud, T, Frank, J, Franke, B, Fraser, C, Freedman, R, Freimer, NB, Freitag, CM, Friedl, M, Frisén, L, Gallagher, L, Gejman, PV, Georgieva, L, Gershon, ES, Geschwind, DH, Giegling, I, Gill, M, Gordon, SD, Gordon-Smith, K, Green, EK, Greenwood, TA, Grice, DE, Gross, M, Grozeva, D, Guan, W, Gurling, H, De Haan, L, Haines, JL, Hakonarson, H, Hallmayer, J, Hamilton, SP, Hamshere, ML, Hansen, TF, Hartmann, AM, Hautzinger, M, Heath, AC, Henders, AK, Herms, S, Hickie, IB, Hipolito, M, Hoefels, S, Holmans, PA, Holsboer, F, Hoogendijk, WJ, Hottenga, JJ, Hultman, CM, Hus, V, Ingason, A, Ising, M, Jamain, S, Jones, EG, Jones, I, Jones, L, Tzeng, JY, Kähler, AK, Kahn, RS, Kandaswamy, R, Keller, MC, Kennedy, JL, Kenny, E, Kent, L, Kim, Y, Kirov, GK, Klauck, SM, Klei, L, Knowles, JA, Kohli, MA, Koller, DL, Konte, B, Korszun, A, Krabbendam, L, Krasucki, R, Kuntsi, J, Kwan, P, Landén, M, Långström, N, Lathrop, M, Lawrence, J, Lawson, WB, Leboyer, M, Ledbetter, DH, Lee, PH, Lencz, T, Lesch, KP, Levinson, DF, Lewis, CM, Li, J, Lichtenstein, P, Lieberman, JA, Lin, DY, Linszen, DH, Liu, C, Lohoff, FW, Loo, SK, Lord, C, Lowe, JK, Lucae, S, MacIntyre, DJ, Madden, PA, Maestrini, E, Magnusson, PK, Mahon, PB, Maier, W, Malhotra, AK, Mane, SM, Martin, CL, Martin, NG, Mattheisen, M, Matthews, K, Mattingsdal, M, McCarroll, SA, McGhee, KA, McGough, JJ, McGrath, PJ, McGuffin, P, McInnis, MG, McIntosh, A, McKinney, R, McLean, AW, McMahon, FJ, McMahon, WM, McQuillin, A, Medeiros, H, Medland, SE, Meier, S, Melle, I, Meng, F, Meyer, J, Middeldorp, CM, Middleton, L, Milanova, V, Miranda, A, Monaco, AP, Montgomery, GW, Moran, JL, Moreno-De-Luca, D, Morken, G, Morris, DW, Morrow, EM, Moskvina, V, Muglia, P, Mühleisen, TW, Muir, WJ, Müller-Myhsok, B, Murtha, M, Myers, RM, Myin-Germeys, I, Neale, MC, Nelson, SF, Nievergelt, CM, Nikolov, I, Nimgaonkar, V, Nolen, WA, Nöthen, MM, Nurnberger, JI, Nwulia, EA, Nyholt, DR, O'Dushlaine, C, Oades, RD, Olincy, A, Oliveira, G, Olsen, L, Ophoff, RA, Osby, U, Owen, MJ, Palotie, A, Parr, JR, Paterson, AD, Pato, CN, Pato, MT, Penninx, BW, Pergadia, ML, Pericak-Vance, MA, Pickard, BS, Pimm, J, Piven, J, Posthuma, D, Potash, JB, Poustka, F, Propping, P, Puri, V, Quested, DJ, Quinn, EM, Ramos-Quiroga, JA, Rasmussen, HB, Raychaudhuri, S, Rehnström, K, Reif, A, Ribasés, M, Rice, JP, Rietschel, M, Roeder, K, Roeyers, H, Rossin, L, Rothenberger, A, Rouleau, G, Ruderfer, D, Rujescu, D, Sanders, AR, Sanders, SJ, Santangelo, SL, Sergeant, JA, Schachar, R, Schalling, M, Schatzberg, AF, Scheftner, WA, Schellenberg, GD, Scherer, SW, Schork, NJ, Schulze, TG, Schumacher, J, Schwarz, M, Scolnick, E, Scott, LJ, Shi, J, Shilling, PD, Shyn, SI, Silverman, JM, Slager, SL, Smalley, SL, Smit, JH, Smith, EN, Sonuga-Barke, EJ, St Clair, D, State, M, Steffens, M, Steinhausen, HC, Strauss, JS, Strohmaier, J, Stroup, TS, Sutcliffe, JS, Szatmari, P, Szelinger, S, Thirumalai, S, Thompson, RC, Todorov, AA, Tozzi, F, Treutlein, J, Uhr, M, van den Oord, EJ, Van Grootheest, G, Van Os, J, Vicente, AM, Vieland, VJ, Vincent, JB, Visscher, PM, Walsh, CA, Wassink, TH, Watson, SJ, Weissman, MM, Werge, T, Wienker, TF, Wijsman, EM, Willemsen, G, Williams, N, Willsey, AJ, Witt, SH, Xu, W, Young, AH, Yu, TW, Zammit, S, Zandi, PP, Zhang, P, Zitman, FG, Zöllner, S, Devlin, B, Kelsoe, JR, Sklar, P, Daly, MJ, O'Donovan, MC, Craddock, N, Sullivan, PF, Smoller, JW, Kendler, KS, Wray, NR; International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics 45, 984994.CrossRefGoogle Scholar
Cutting, JC, Shepherd, M (1987). The Clinical Roots of the Schizophrenia Concept: Translations of Seminal European Contributions on Schizophrenia. Cambridge University Press: New York.Google Scholar
Damyanova, V, Dimitrova-Dikanarova, D, Hadjidekova, S, Savov, A, Nesheva, D, Rukova, B, Vatev, I, Toncheva, D (2013). [Genomic study in patients with idiopathic azoospermia and oligoasthenoteratozoospermia] [article in Bulgarian]. Akusherstvo i Ginekologiia 52, 2734.Google Scholar
Delaneau, O, Marchini, J, Zagury, JF (2012). A linear complexity phasing method for thousands of genomes. Nature Methods 9, 179181.CrossRefGoogle ScholarPubMed
EPICURE Consortium, EMINet Consortium, Steffens, M, Leu, C, Ruppert, AK, Zara, F, Striano, P, Robbiano, A, Capovilla, G, Tinuper, P, Gambardella, A, Bianchi, A, La Neve, A, Crichiutti, G, de Kovel, CG, Kasteleijn-Nolst Trenite, D, de Haan, GJ, Lindhout, D, Gaus, V, Schmitz, B, Janz, D, Weber, YG, Becker, F, Lerche, H, Steinhoff, BJ, Kleefuss-Lie, AA, Kunz, WS, Surges, R, Elger, CE, Muhle, H, von Spiczak, S, Ostertag, P, Helbig, I, Stephani, U, Moller, RS, Hjalgrim, H, Dibbens, LM, Bellows, S, Oliver, K, Mullen, S, Scheffer, IE, Berkovic, SF, Everett, KV, Gardiner, MR, Marini, C, Guerrini, R, Lehesjoki, AE, Siren, A, Guipponi, M, Malafosse, A, Thomas, P, Nabbout, R, Baulac, S, Leguern, E, Guerrero, R, Serratosa, JM, Reif, PS, Rosenow, F, Morzinger, M, Feucht, M, Zimprich, F, Kapser, C, Schankin, CJ, Suls, A, Smets, K, De Jonghe, P, Jordanova, A, Caglayan, H, Yapici, Z, Yalcin, DA, Baykan, B, Bebek, N, Ozbek, U, Gieger, C, Wichmann, HE, Balschun, T, Ellinghaus, D, Franke, A, Meesters, C, Becker, T, Wienker, TF, Hempelmann, A, Schulz, H, Ruschendorf, F, Leber, M, Pauck, SM, Trucks, H, Toliat, MR, Nurnberg, P, Avanzini, G, Koeleman, BP, Sander, T (2012). Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32. Human Molecular Genetics 21, 53595372.Google ScholarPubMed
Fabregat-Traver, D, Sharapov, SZh, Hayward, C, Rudan, I, Campbell, H, Aulchenko, Y, Bientinesi, P (2014). High-performance mixed models based genome-wide association analysis with omicABEL software. F1000Res 3, 200.Google ScholarPubMed
Ferrarelli, F, Peterson, MJ, Sarasso, S, Riedner, BA, Murphy, MJ, Benca, RM, Bria, P, Kalin, NH, Tononi, G (2010). Thalamic dysfunction in schizophrenia suggested by whole-night deficits in slow and fast spindles. American Journal of Psychiatry 167, 13391348.CrossRefGoogle ScholarPubMed
Gibbons, AS, Scarr, E, McLean, C, Sundram, S, Dean, B (2009). Decreased muscarinic receptor binding in the frontal cortex of bipolar disorder and major depressive disorder subjects. Journal of Affective Disorders 116, 184191.CrossRefGoogle ScholarPubMed
Hibar, DP, Stein, JL, Renteria, ME, Arias-Vasquez, A, Desrivières, S, Jahanshad, N, Toro, R, Wittfeld, K, Abramovic, L, Andersson, M, Aribisala, BS, Armstrong, NJ, Bernard, M, Bohlken, MM, Boks, MP, Bralten, J, Brown, AA, Mallar Chakravarty, M, Chen, Q, Ching, CR, Cuellar-Partida, G, den Braber, A, Giddaluru, S, Goldman, AL, Grimm, O, Guadalupe, T, Hass, J, Woldehawariat, G, Holmes, AJ, Hoogman, M, Janowitz, D, Jia, T, Kim, S, Klein, M, Kraemer, B, Lee, PH, Olde Loohuis, LM, Luciano, M, Macare, C, Mather, KA, Mattheisen, M, Milaneschi, Y, Nho, K, Papmeyer, M, Ramasamy, A, Risacher, SL, Roiz-Santiañez, R, Rose, EJ, Salami, A, Sämann, PG, Schmaal, L, Schork, AJ, Shin, J, Strike, LT, Teumer, A, van Donkelaar, MM, van Eijk, KR, Walters, RK, Westlye, LT, Whelan, CD, Winkler, AM, Zwiers, MP, Alhusaini, S, Athanasiu, L, Ehrlich, S, Hakobjan, MM, Hartberg, CB, Haukvik, UK, Heister, AJ, Hoehn, D, Kasperaviciute, D, Liewald, DC, Lopez, LM, Makkinje, RRR, Matarin, M, Naber, MA, Reese McKay, D, Needham, M, Nugent, AC, Pütz, B, Royle, NA, Shen, L, Sprooten, E, Trabzuni, D, van der Marel, SS, van Hulzen, KJ, Walton, E, Wolf, C, Almasy, L, Ames, D, Arepalli, S, Assareh, AA, Bastin, ME, Brodaty, H, Bulayeva, KB, Carless, MA, Cichon, S, Corvin, A, Curran, JE, Czisch, M (2015). Common genetic variants influence human subcortical brain structures. Nature 520, 224229.CrossRefGoogle ScholarPubMed
Howie, BN, Donnelly, P, Marchini, J (2009). A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genetics 5, e1000529.CrossRefGoogle ScholarPubMed
Joel, SE, Caffo, BS, van Zijl, P, Pekar, JJ (2011). On the relationship between seed-based and ICA-based measures of functional connectivity. Magnetic Resonance in Medicine 66, 644657.CrossRefGoogle ScholarPubMed
Kim, DI, Manoach, DS, Mathalon, DH, Turner, JA, Mannell, M, Brown, GG, Ford, JM, Gollub, RL, White, T, Wible, C (2009). Dysregulation of working memory and default-mode networks in schizophrenia using independent component analysis, an fBIRN and MCIC study. Human Brain Mapping 30, 37953811.CrossRefGoogle ScholarPubMed
Klingner, CM, Langbein, K, Dietzek, M, Smesny, S, Witte, OW, Sauer, H, Nenadic, I (2014). Thalamocortical connectivity during resting state in schizophrenia. European Archives of Psychiatry and Clinical Neuroscience 264, 111119.CrossRefGoogle Scholar
Li, MX, Gui, HS, Kwan, JS, Sham, PC (2011). GATES: a rapid and powerful gene-based association test using extended Simes procedure. American Journal of Human Genetics 88, 283293.CrossRefGoogle ScholarPubMed
McGuffin, P, Farmer, AE, Gottesman, II, Murray, RM, Reveley, AM (1984). Twin concordance for operationally defined schizophrenia: confirmation of familiality and heritability. Archives of General Psychiatry 41, 541545.CrossRefGoogle ScholarPubMed
Morten, LK (2005). The human orbitofrontal cortex: linking reward to hedonic experience. Nature Reviews Neuroscience 6, 691702.Google Scholar
Nakamura, M, Nestor, PG, Levitt, JJ, Cohen, AS, Kawashima, T, Shenton, ME, McCarley, RW (2008). Orbitofrontal volume deficit in schizophrenia and thought disorder. Brain 131, 180195.CrossRefGoogle Scholar
O'Donovan, MC, Craddock, N, Norton, N, Williams, H, Peirce, T, Moskvina, V, Nikolov, I, Hamshere, M, Carroll, L, Georgieva, L (2008). Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nature Genetics 40, 10531055.CrossRefGoogle ScholarPubMed
O'Reilly, PF, Hoggart, CJ, Pomyen, Y, Calboli, FC, Elliott, P, Jarvelin, MR, Coin, LJ (2012). MultiPhen: joint model of multiple phenotypes can increase discovery in GWAS. PLOS ONE 7, e34861.CrossRefGoogle ScholarPubMed
Petersen, AK, Ahmad, A, Shafiq, M, Brown-Kipphut, B, Fong, CT, Anwar Iqbal, M (2013). Deletion 1q43 encompassing only CHRM3 in a patient with autistic disorder. European Journal of Medical Genetics 56, 118122.CrossRefGoogle Scholar
Pettersson-Yeo, W, Allen, P, Benetti, S, McGuire, P, Mechelli, A (2011). Dysconnectivity in schizophrenia: where are we now? Neuroscience and Biobehavioral Reviews 35, 11101124.CrossRefGoogle ScholarPubMed
Pirastu, N, Kooyman, M, Traglia, M, Robino, A, Willems, SM, Pistis, G, Amin, N, Sala, C, Karssen, LC, van Duijn, CM, Toniolo, D, Gasparini, P (2015). Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking. European Journal of Human Genetics 23, 17171722.CrossRefGoogle Scholar
Potkin, S, Turner, J, Brown, G, McCarthy, G, Greve, D, Glover, G, Manoach, D, Belger, A, Diaz, M, Wible, C (2009 a). Working memory and DLPFC inefficiency in schizophrenia: the FBIRN study. Schizophrenia Bulletin 35, 1931.CrossRefGoogle ScholarPubMed
Potkin, SG, Turner, JA, Guffanti, G, Lakatos, A, Fallon, JH, Nguyen, DD, Mathalon, D, Ford, J, Lauriello, J, Macciardi, F (2009 b). A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype. Schizophrenia Bulletin 35, 96108.CrossRefGoogle Scholar
Poulin, B, Butcher, A, McWilliams, P, Bourgognon, JM, Pawlak, R, Kong, KC, Bottrill, A, Mistry, S, Wess, J, Rosethorne, EM, Charlton, SJ, Tobin, AB (2010). The M3-muscarinic receptor regulates learning and memory in a receptor phosphorylation/arrestin-dependent manner. Proceedings of the National Academy of Science USA 107, 94409445.CrossRefGoogle Scholar
Pruim, RJ, Welch, RP, Sanna, S, Teslovich, TM, Chines, PS, Gliedt, TP, Boehnke, M, Abecasis, GR, Willer, CJ (2010). LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26, 23362337.CrossRefGoogle ScholarPubMed
Sawa, A, Snyder, SH (2002). Schizophrenia: diverse approaches to a complex disease. Science 296, 692695.CrossRefGoogle ScholarPubMed
Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (2011). Genome-wide association study identifies five new schizophrenia loci. Nature Genetics 43, 969976.CrossRefGoogle ScholarPubMed
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421427.CrossRefGoogle ScholarPubMed
Shi, Y, Li, Z, Xu, Q, Wang, T, Li, T, Shen, J, Zhang, F, Chen, J, Zhou, G, Ji, W, Li, B, Xu, Y, Liu, D, Wang, P, Yang, P, Liu, B, Sun, W, Wan, C, Qin, S, He, G, Steinberg, S, Cichon, S, Werge, T, Sigurdsson, E, Tosato, S, Palotie, A, Nothen, MM, Rietschel, M, Ophoff, RA, Collier, DA, Rujescu, D, Clair, DS, Stefansson, H, Stefansson, K, Ji, J, Wang, Q, Li, W, Zheng, L, Zhang, H, Feng, G, He, L (2011). Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. Nature Genetics 43, 12241227.CrossRefGoogle ScholarPubMed
Stein, JL, Medland, SE, Vasquez, AA, Hibar, DP, Senstad, RE, Winkler, AM, Toro, R, Appel, K, Bartecek, R, Bergmann, O, Bernard, M, Brown, AA, Cannon, DM, Chakravarty, MM, Christoforou, A, Domin, M, Grimm, O, Hollinshead, M, Holmes, AJ, Homuth, G, Hottenga, JJ, Langan, C, Lopez, LM, Hansell, NK, Hwang, KS, Kim, S, Laje, G, Lee, PH, Liu, X, Loth, E, Lourdusamy, A, Mattingsdal, M, Mohnke, S, Maniega, SM, Nho, K, Nugent, AC, O'Brien, C, Papmeyer, M, Putz, B, Ramasamy, A, Rasmussen, J, Rijpkema, M, Risacher, SL, Roddey, JC, Rose, EJ, Ryten, M, Shen, L, Sprooten, E, Strengman, E, Teumer, A, Trabzuni, D, Turner, J, van Eijk, K, van Erp, TG, van Tol, MJ, Wittfeld, K, Wolf, C, Woudstra, S, Aleman, A, Alhusaini, S, Almasy, L, Binder, EB, Brohawn, DG, Cantor, RM, Carless, MA, Corvin, A, Czisch, M, Curran, JE, Davies, G, de Almeida, MA, Delanty, N, Depondt, C, Duggirala, R, Dyer, TD, Erk, S, Fagerness, J, Fox, PT, Freimer, NB, Gill, M, Goring, HH, Hagler, DJ, Hoehn, D, Holsboer, F, Hoogman, M, Hosten, N, Jahanshad, N, Johnson, MP, Kasperaviciute, D, Kent, JW Jr., Kochunov, P, Lancaster, JL, Lawrie, SM, Liewald, DC, Mandl, R, Matarin, M, Mattheisen, M, Meisenzahl, E, Melle, I, Moses, EK, Muhleisen, TW, Nauck, M, Nothen, MM, Olvera, RL, Pandolfo, M, Pike, GB, Puls, R, Reinvang, I, Renteria, ME, Rietschel, M, Roffman, JL, Royle, NA, Rujescu, D, Savitz, J, Schnack, HG, Schnell, K, Seiferth, N, Smith, C, Steen, VM, Valdes Hernandez, MC, Van den Heuvel, M, van der Wee, NJ, Van Haren, NE, Veltman, JA, Volzke, H, Walker, R, Westlye, LT, Whelan, CD, Agartz, I, Boomsma, DI, Cavalleri, GL, Dale, AM, Djurovic, S, Drevets, WC, Hagoort, P, Hall, J, Heinz, A, Jack, CR Jr., Foroud, TM, Le Hellard, S, Macciardi, F, Montgomery, GW, Poline, JB, Porteous, DJ, Sisodiya, SM, Starr, JM, Sussmann, J, Toga, AW, Veltman, DJ, Walter, H, Weiner, MW, Bis, JC, Ikram, MA, Smith, AV, Gudnason, V, Tzourio, C, Vernooij, MW, Launer, LJ, DeCarli, C, Seshadri, S, Andreassen, OA, Apostolova, LG, Bastin, ME, Blangero, J, Brunner, HG, Buckner, RL, Cichon, S, Coppola, G, de Zubicaray, GI, Deary, IJ, Donohoe, G, de Geus, EJ, Espeseth, T, Fernandez, G, Glahn, DC, Grabe, HJ, Hardy, J, Hulshoff Pol, HE, Jenkinson, M, Kahn, RS, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Meyer-Lindenberg, A, Morris, DW, Muller-Myhsok, B, Nichols, TE, Ophoff, RA, Paus, T, Pausova, Z, Penninx, BW, Potkin, SG, Samann, PG, Saykin, AJ, Schumann, G, Smoller, JW, Wardlaw, JM, Weale, ME, Martin, NG, Franke, B, Wright, MJ, Thompson, PM (2012). Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics 44, 552561.CrossRefGoogle ScholarPubMed
Svishcheva, GR, Axenovich, TI, Belonogova, NM, van Duijn, CM, Aulchenko, YS (2012). Rapid variance components-based method for whole-genome association analysis. Nature Genetics 44, 11661170.CrossRefGoogle ScholarPubMed
Van der Sluis, S, Dolan, CV, Li, J, Song, Y, Sham, P, Posthuma, D, Li, MX (2015). MGAS: a powerful tool for multivariate gene-based genome-wide association analysis. Bioinformatics 31, 10071015.CrossRefGoogle ScholarPubMed
van der Sluis, S, Posthuma, D, Dolan, CV (2013). TATES: efficient multivariate genotype–phenotype analysis for genome-wide association studies. PLoS Genetics 9, e1003235.CrossRefGoogle ScholarPubMed
van Os, J, Kapur, S (2009). Schizophrenia. Lancet 374, 635645.CrossRefGoogle ScholarPubMed
Wang, Q, Xiang, B, Deng, W, Wu, J, Li, M, Ma, X, Wang, Y, Jiang, L, McAlonan, G, Chua, SE, Sham, PC, Hu, X, Li, T (2013). Genome-wide association analysis with gray matter volume as a quantitative phenotype in first-episode treatment-naive patients with schizophrenia. PLOS One 8, e75083.Google ScholarPubMed
Weinberger, DR, Egan, MF, Bertolino, A, Callicott, JH, Mattay, VS, Lipska, BK, Berman, KF, Goldberg, TE (2001). Prefrontal neurons and the genetics of schizophrenia. Biological Psychiatry 50, 825844.CrossRefGoogle Scholar
Welsh, RC, Chen, AC, Taylor, SF (2008). Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in schizophrenia. Schizophrenia Bulletin 36, 713722.CrossRefGoogle Scholar
Woodward, ND, Karbasforoushan, H, Heckers, S (2012). Thalamocortical dysconnectivity in schizophrenia. American Journal of Psychiatry 169, 10921099.CrossRefGoogle Scholar
Yue, WH, Wang, HF, Sun, LD, Tang, FL, Liu, ZH, Zhang, HX, Li, WQ, Zhang, YL, Zhang, Y, Ma, CC, Du, B, Wang, LF, Ren, YQ, Yang, YF, Hu, XF, Wang, Y, Deng, W, Tan, LW, Tan, YL, Chen, Q, Xu, GM, Yang, GG, Zuo, XB, Yan, H, Ruan, YY, Lu, TL, Han, X, Ma, XH, Cai, LW, Jin, C, Zhang, HY, Yan, J, Mi, WF, Yin, XY, Ma, WB, Liu, Q, Kang, L, Sun, W, Pan, CY, Shuang, M, Yang, FD, Wang, CY, Yang, JL, Li, KQ, Ma, X, Li, LJ, Yu, X, Li, QZ, Huang, X, Lv, LX, Li, T, Zhao, GP, Huang, W, Zhang, XJ, Zhang, D (2011). Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. Nature Genetics 43, 12281231.CrossRefGoogle Scholar

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The CHRM3 gene is implicated in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia
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The CHRM3 gene is implicated in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia
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