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Dissecting the association between psychiatric disorders and neurological proteins: a genetic correlation and two-sample bidirectional Mendelian randomization study

Published online by Cambridge University Press:  28 March 2022

Huimei Huang ,
Shiqiang Cheng Open the ORCID record for Shiqiang Cheng [Opens in a new window] ,
Chun’e Li ,
Bolun Cheng ,
Li Liu ,
Xuena Yang ,
Peilin Meng ,
Yao Yao ,
Chuyu Pan  and
Jingxi Zhang
...Show all authors
Huimei Huang
Affiliation:
Department of Nephrology, Xi’an Children’s Hospital, The Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, China
Shiqiang Cheng
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Chun’e Li
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Bolun Cheng
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Li Liu
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Xuena Yang
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Peilin Meng
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yao Yao
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Chuyu Pan
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Jingxi Zhang
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Huijie Zhang
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yujing Chen
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Zhen Zhang
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yan Wen
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Yumeng Jia
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
Feng Zhang*
Affiliation:
Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission; Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education of China; Key Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
*
Author for correspondence: Feng Zhang, Email: fzhxjtu@xjtu.edu.cn
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Abstract

Objectives:

The role of neurological proteins in the development of bipolar disorder (BD) and schizophrenia (SCZ) remains elusive now. The current study aims to explore the potential genetic correlations of plasma neurological proteins with BD and SCZ.

Methods:

By using the latest genome-wide association study (GWAS) summary data of BD and SCZ (including 41,917 BD cases, 11,260 SCZ cases, and 396,091 controls) derived from the Psychiatric GWAS Consortium website (PGC) and a recently released GWAS of neurological proteins (including 750 individuals), we performed a linkage disequilibrium score regression (LDSC) analysis to detect the potential genetic correlations between the two common psychiatric disorders and each of the 92 neurological proteins. Two-sample Mendelian randomisation (MR) analysis was then applied to assess the bidirectional causal relationship between the neurological proteins identified by LDSC, BD and SCZ.

Results:

LDSC analysis identified one neurological protein, NEP, which shows suggestive genetic correlation signals for both BD (coefficient = −0.165, p value = 0.035) and SCZ (coefficient = −0.235, p value = 0.020). However, those association did not remain significant after strict Bonferroni correction. Two sample MR analysis found that there was an association between genetically predicted level of NEP protein, BD (odd ratio [OR] = 0.87, p value = 1.61 × 10−6) and SCZ (OR = 0.90, p value = 4.04 × 10−6). However, in the opposite direction, there is no genetically predicted association between BD, SCZ, and NEP protein level.

Conclusion:

This study provided novel clues for understanding the genetic effects of neurological proteins on BD and SCZ.

Keywords

bipolar disorderschizophrenialinkage disequilibrium score regressionneurological proteingenetic correlation
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 34 , Issue 6 , December 2022 , pp. 311 - 317
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Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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Footnotes

Huimei Huang and Shiqiang Cheng contributed equally to this work and share first authorship.

References

Arango, C, Diazcaneja, CM, Mcgorry, PD, Rapoport, JL, Sommer, IEC, Vorstman, J, Mcdaid, D, Marin, O, Serranodrozdowskyj, E, Freedman, R (2018) Preventive strategies for mental health. The Lancet Psychiatry 5(7), 591–604.CrossRefGoogle ScholarPubMed
Boules, M, Shaw, A, Fredrickson, P and Richelson, E (2007) Neurotensin agonists: potential in the treatment of schizophrenia. CNS Drugs 21(1), 13–23.CrossRefGoogle ScholarPubMed
Brion, MJ, Shakhbazov, K and Visscher, PM (2013) Calculating statistical power in Mendelian randomization studies. International Journal of Epidemiology 42(5), 1497–1501.CrossRefGoogle ScholarPubMed
Bulik-Sullivan, B, Finucane, HK, Anttila, V, Gusev, A, Day, FR, ReproGen Consortium; Psychiatric Genomics Consortium; Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3, Duncan, L, Perry, JRB, Patterson, N, Robinson, E, Daly, MJ, Price, AL and Neale, BM (2015) An atlas of genetic correlations across human diseases and traits. Nature Genetics 47(11), 1236–1241.CrossRefGoogle ScholarPubMed
Burgess, S, Butterworth, A and Thompson, SG (2013) Mendelian randomization analysis with multiple genetic variants using summarized data. Genetic Epidemiology 37(7), 658–665.CrossRefGoogle ScholarPubMed
Burgess, S, Small, DS and Thompson, SG (2015) A review of instrumental variable estimators for Mendelian randomization. Statistical Methods in Medical Research 26(5), 2333–2355.CrossRefGoogle ScholarPubMed
Consortium, SWGOTPG (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511(7510), 421–427.Google Scholar
Finseth, PI, Sønderby, IE, Djurovic, S, Agartz, I, Malt, UF, Melle, I, Morken, G, Andreassen, OA, Vaaler, AE, Tesli, M (2014) Association analysis between suicidal behaviour and candidate genes of bipolar disorder and schizophrenia. Journal of Affective Disorders 163, 110–114.CrossRefGoogle ScholarPubMed
Gaunt, TR, Shihab, HA, Hemani, G, Min, JL, Woodward, G, Lyttleton, O, Zheng, J, Duggirala, A, Mcardle, WL, Ho, K, Ring, SM, Evans, DM, Davey Smith, G, Relton, CL (2016) Systematic identification of genetic influences on methylation across the human life course. Genome Biology 17, 61.CrossRefGoogle ScholarPubMed
Gratacòs, M, Costas, J, de Cid, R, Bayés, M, González, JR, Baca-García, E, de Diego, Y, Fernández-Aranda, F, Fernández-Piqueras, J, Guitart, M, Martín-Santos, R, Martorell, L, Menchón, JM, Roca, M, Sáiz-Ruiz, J, Sanjuán, J, Torrens, M, Urretavizcaya, M, Valero, J, Vilella, E, Estivill, X and Carracedo, Á (2009) Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment. American Journal of Medical Genetics. Part B 150B(6), 808–816.CrossRefGoogle ScholarPubMed
Gürel, Ç., Kuşçu, GC, Yavaşoğlu, A and Biray Avcı, Ç. (2020) The clues in solving the mystery of major psychosis: the epigenetic basis of schizophrenia and bipolar disorder. Neuroscience & Biobehavioral Reviews 113(519), 51–61.CrossRefGoogle ScholarPubMed
Hillary, RF, Mccartney, DL, Harris, SE, Stevenson, AJ, Seeboth, A, Zhang, Q, Liewald, DC, Evans, KL, Ritchie, CW, Tucker-Drob, EM, Wray, NR, Mcrae, AF, Visscher, PM, Deary, IJ, Marioni, RE (2019) Genome and epigenome wide studies of neurological protein biomarkers in the Lothian Birth Cohort 1936. Nature Communications 10, 3160.CrossRefGoogle ScholarPubMed
James, SL, Abate, D, Abate, KH, Abay, SM, Abbafati, C, Abbasi, N, Abbastabar, H, Abd-Allah, F, Abdela, J, Abdelalim, A, Abdollahpour, I, Abdulkader, RS, Abebe, Z, Abera, SF, Abil, OZ, Abraha, HN, Abu-Raddad, LJ, Abu-Rmeileh, NME, Accrombessi, MMK, Acharya, D, Acharya, P, Ackerman, IN, Adamu, AA, Adebayo, OM, Adekanmbi, V, Adetokunboh, OO, Adib, MG, Adsuar, JC, Afanvi, KA, Afarideh, M, Afshin, A, Agarwal, G, Agesa, KM, Aggarwal, R, Aghayan, SA, Agrawal, S, Ahmadi, A, Ahmadi, M, Ahmadieh, H, Ahmed, MB, Aichour, AN, Aichour, I, Aichour, MTE, Akinyemiju, T, Akseer, N, Al-Aly, Z, Al-Eyadhy, A, Al-Mekhlafi, HM, Al-Raddadi, RM, Alahdab, F, Alam, K, Alam, T, Alashi, A, Alavian, SM, Alene, KA, Alijanzadeh, M, Alizadeh-Navaei, R, Aljunid, SM, Alkerwi, AA, Alla, F, Allebeck, P, Alouani, MML, Altirkawi, K, Alvis-Guzman, N, Amare, AT, Aminde, LN, Ammar, W, Amoako, YA, Anber, NH, Andrei, CL, Androudi, S, Animut, MD, Anjomshoa, M, Ansha, MG, Antonio, CAT, Anwari, P, Arabloo, J, Arauz, A, Aremu, O, Ariani, F, Armoon, B, Ärnlöv, J, Arora, A, Artaman, A, Aryal, KK, Asayesh, H, Asghar, RJ, Ataro, Z, Atre, SR, Ausloos, M, Avila-Burgos, L, Avokpaho, EFGA, Awasthi, A, Ayala Quintanilla, BP, Ayer, R, Azzopardi, PS, Babazadeh, A, Badali, H, Badawi, A, Bali, AG, et al. (2018) Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet 392(10159), 1789–1858.CrossRefGoogle Scholar
Kappelmann, N, Arloth, J, Georgakis, MK, Czamara, D, Rost, N, Ligthart, S, Khandaker, GM and Binder, EB (2021) Dissecting the association between inflammation, metabolic dysregulation, and specific depressive symptoms: a genetic correlation and 2-sample Mendelian randomization study. JAMA Psychiatry 78(2), 161–170.CrossRefGoogle ScholarPubMed
Lee, JJ and Chow, CCJB (2017) LD Score regression as an estimator of confounding and genetic correlations in genome-wide association studies. bioRxiv, 234815.CrossRefGoogle Scholar
Li, M, Shen, L, Chen, L, Huai, C, Huang, H, Wu, X, Yang, C, Ma, J, Zhou, W, Du, H, Fan, L, He, L, Wan, C, Qin, S (2020) Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients. Translational Psychiatry 10(1), 5.CrossRefGoogle ScholarPubMed
Lichtenstein, P, Yip, BH, Björk, C, Pawitan, Y, Cannon, TD, Sullivan, PF and Hultman, CM (2009) Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. The Lancet 373(9659), 234–239.CrossRefGoogle ScholarPubMed
Mullins, N, Forstner, AJ, O’connell, KS, Coombes, B, Coleman, JRI, Qiao, Z, Als, TD, Bigdeli, TB, Børte, S, Bryois, J, Charney, AW, Drange, OK, Gandal, MJ, Hagenaars, SP, Ikeda, M, Kamitaki, N, Kim, M, Krebs, K, Panagiotaropoulou, G, Schilder, BM, Sloofman, LG, Steinberg, S, Trubetskoy, V, Winsvold, BS, Won, HH, Abramova, L, Adorjan, K, Agerbo, E, Al Eissa, M, Albani, D, Alliey-Rodriguez, N, Anjorin, A, Antilla, V, Antoniou, A, Awasthi, S, Baek, JH, Bækvad-Hansen, M, Bass, N, Bauer, M, Beins, EC, Bergen, SE, Birner, A, BØCKER Pedersen, C, Bøen, E, Boks, MP, Bosch, R, Brum, M, Brumpton, BM, Brunkhorst-Kanaan, N, Budde, M, Bybjerg-Grauholm, J, Byerley, W, Cairns, M, Casas, M, Cervantes, P, Clarke, TK, Cruceanu, C, Cuellar-Barboza, A, Cunningham, J, Curtis, D, Czerski, PM, Dale, AM, Dalkner, N, David, FS, Degenhardt, F, Djurovic, S, Dobbyn, AL, Douzenis, A, Elvsåshagen, T, Escott-Price, V, Ferrier, IN, Fiorentino, A, Foroud, TM, Forty, L, Frank, J, Frei, O, Freimer, NB, Frisén, L, Gade, K, Garnham, J, Gelernter, J, Giørtz Pedersen, M, Gizer, IR, Gordon, SD, Gordon-Smith, K, Greenwood, TA, Grove, J, Guzman-Parra, J, Ha, K, Haraldsson, M, Hautzinger, M, Heilbronner, U, Hellgren, D, Herms, S, Hoffmann, P, Holmans, PA, Huckins, L, Jamain, S, Johnson, JS, Kalman, JL, et al. (2021) Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature Genetics 53, 817–829.CrossRefGoogle ScholarPubMed
Nohesara, S, Ghadirivasfi, M, Mostafavi, S, Eskandari, M-R, Ahmadkhaniha, H, Thiagalingam, S and Abdolmaleky, HM (2011) DNA hypomethylation of MB-COMT promoter in the DNA derived from saliva in schizophrenia and bipolar disorder. Journal of Psychiatric Research 45(11), 1432–1438.CrossRefGoogle ScholarPubMed
Pai, S, P., LI, Killinger, B, Marshall, L, Jia, P, Liao, J, Petronis, A, Szabó, PE and Labrie, V (2019) Differential methylation of enhancer at IGF2 is associated with abnormal dopamine synthesis in major psychosis. Nature Communications 10, 2046.CrossRefGoogle ScholarPubMed
Pardiñas, AF, Holmans, P, Pocklington, AJ, Escott-Price, V, Ripke, S, Carrera, N, Legge, SE, Bishop, S, Cameron, D, Hamshere, ML, Han, J, Hubbard, L, Lynham, A, Mantripragada, K, Rees, E, Maccabe, JH, Mccarroll, SA, Baune, BT, Breen, G, Byrne, EM, Dannlowski, U, Eley, TC, Hayward, C, Martin, NG, Mcintosh, AM, Plomin, R, Porteous, DJ, Wray, NR, Caballero, A, Geschwind, DH, Huckins, LM, Ruderfer, DM, Santiago, E, Sklar, P, Stahl, EA, Won, H, Agerbo, E, Als, TD, Andreassen, OA, Bækvad-Hansen, M, Mortensen, PB, Pedersen, CB, Børglum, AD, Bybjerg-Grauholm, J, Djurovic, S, Durmishi, N, Pedersen, MG, Golimbet, V, Grove, J, Hougaard, DM, Mattheisen, M, Molden, E, Mors, O, Nordentoft, M, Pejovic-Milovancevic, M, Sigurdsson, E, Silagadze, T, Hansen, CS, Stefansson, K, Stefansson, H, Steinberg, S, Tosato, S, Werge, T, Harold, D, Sims, R, Gerrish, A, Chapman, J, Escott-Price, V, Abraham, R, Hollingworth, P, Pahwa, J, Denning, N, Thomas, C, Taylor, S, Powell, J, Proitsi, P, Lupton, M, Lovestone, S, Passmore, P, Craig, D, Mcguinness, B, Johnston, J, Todd, S, Maier, W, Jessen, F, Heun, R, Schurmann, B, Ramirez, Z, Becker, T, Herold, C, Lacour, A, Drichel, D, Nothen, M, Goate, A, Cruchaga, C, Nowotny, P, Morris, JC, Mayo, K, Holmans, P, O’donovan, M, et al. (2018) Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nature Genetics 50, 381–389.CrossRefGoogle ScholarPubMed
Perreault, ML, Hasbi, A, Alijaniaram, M, Fan, T, Varghese, G, Fletcher, PJ, Seeman, P, O’dowd, BF and George, SR (2010) The dopamine D1-D2 receptor heteromer localizes in dynorphin/enkephalin neurons: increased high affinity state following amphetamine and in schizophrenia. Journal of Biological Chemistry 285(47), 36625–36634.CrossRefGoogle Scholar
Pierce, BL, Ahsan, H and Vanderweele, TJ (2011) Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants. International Journal of Epidemiology 40(3), 740–752.CrossRefGoogle ScholarPubMed
Porcu, E, Rüeger, S, Lepik, K, Agbessi, M, Ahsan, H, Alves, I, Andiappan, A, Arindrarto, W, Awadalla, P, Battle, A, Beutner, F, Jan Bonder, M, Boomsma, D, Christiansen, M, Claringbould, A, Deelen, P, Esko, T, Favé, M-J, Franke, L, Frayling, T, Gharib, S A, Gibson, G, Heijmans, B T, Hemani, G, Jansen, R, Kähönen, M, Kalnapenkis, A, Kasela, S, Kettunen, J, Kim, Y, Kirsten, H, Kovacs, P, Krohn, K, Kronberg-Guzman, J, Kukushkina, V, Lee, B, Lehtimäki, T, Loeffler, M, Marigorta, U M, Mei, H, Milani, L, Montgomery, G W, Müller-Nurasyid, M, Nauck, M, Nivard, M, Penninx, B, Perola, M, Pervjakova, N, Pierce, B L, Powell, J, Prokisch, H, Psaty, B M, Raitakari, O T, Ripatti, S, Rotzschke, O, Saha, A, Scholz, M, Schramm, K, Seppälä, I, Slagboom, E P, Stehouwer, C D A, Stumvoll, M, Sullivan, P, ‘t Hoen, P A C, Teumer, A, Thiery, J, Tong, L, Tönjes, A, van Dongen, J, van Iterson, M, van Meurs, J, Veldink, J H, Verlouw, J, Visscher, P M, Völker, U, Võsa, U, Westra, H-J, Wijmenga, C, Yaghootkar, H, Yang, J, Zeng, B, Zhang, F, Arindrarto, W, Beekman, M, Boomsma, D I, Bot, J, Deelen, J, Deelen, P, Franke, L, Heijmans, B T, ’t Hoen, P A C, Hofman, B A, Hottenga, J J, Isaacs, A, Bonder, M J, Jhamai, P M, Jansen, R, Kielbasa, S M, Lakenberg, N, Luijk, R, et al. (2019) Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits. Nature Communications 10, 3300.CrossRefGoogle ScholarPubMed
Qi, X, Wen, Y, P., LI, Liang, C, Cheng, B, Ma, M, Cheng, S, Zhang, L, Liu, L, Kafle, OP, Zhang, F (2020) An integrative analysis of genome-wide association study and regulatory SNP annotation datasets identified candidate genes for bipolar disorder. International Journal of Bipolar Disorders 8(1), 6.CrossRefGoogle ScholarPubMed
Ripke, S, O’dushlaine, C, Chambert, K, Moran, JL, Kähler, AK, Akterin, S, Bergen, SE, Collins, AL, Crowley, JJ, Fromer, M, Kim, Y, Lee, SH, Magnusson, PK, Sanchez, N, Stahl, EA, Williams, S, Wray, NR, Xia, K, Bettella, F, Borglum, AD, Bulik-Sullivan, BK, Cormican, P, Craddock, N, De Leeuw, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, ML, Holmans, P, Hougaard, DM, Kendler, KS, Lin, K, Morris, DW, Mors, O, Mortensen, PB, Neale, BM, O’neill, FA, Owen, MJ, Milovancevic, MP, Posthuma, D, Powell, J, Richards, AL, Riley, BP, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, AB, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, S, Verhage, M, Walters, JT, Levinson, DF, Gejman, PV, Kendler, KS, Laurent, C, Mowry, BJ, O’donovan, MC, Owen, MJ, Pulver, AE, Riley, BP, Schwab, SG, Wildenauer, DB, Dudbridge, F, Alexander, M, Holmans, P, Shi, J, Albus, M, Campion, D, Cohen, D, Dikeos, D, Duan, J, Eichhammer, P, Godard, S, Lerer, FM, Hansen, M, Liang, KY, Maier, W, Mallet, J, Nertney, DA, Nestadt, G, Nestadt, G, Norton, N, O’neill, FA, Papadimitriou, GN, Ribble, R, Sanders, AR, Silverman, JM, Walsh, D, Williams, NM, Wormley, B, Arranz, MJ, Bakker, S, Bender, S, Bramon, E, Collier, D, Crespo-Facorro, B, Hall, J, Iyegbe, C, et al. (2013) Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics 45, 1150–1159.CrossRefGoogle Scholar
Shi, H, Kichaev, G and Pasaniuc, B (2016) Contrasting the genetic architecture of 30 complex traits from summary association data. American Journal of Human Genetics 99, 139–153.CrossRefGoogle ScholarPubMed
Sklar, P, Ripke, S, Scott, LJ, Andreassen, OA, Cichon, S, Craddock, N, Edenberg, HJ, Nurnberger, JI, Rietschel, M, Blackwood, D, Corvin, A, Flickinger, M, Guan, W, Mattingsdal, M, Mcquillin, A, Kwan, P, Wienker, TF, Daly, M, Dudbridge, F, Holmans, PA, Lin, D, Burmeister, M, Greenwood, TA, Hamshere, ML, Muglia, P, Smith, EN, Zandi, PP, Nievergelt, CM, Mckinney, R, Shilling, PD, Schork, NJ, Bloss, CS, Foroud, T, Koller, DL, Gershon, ES, Liu, C, Badner, JA, Scheftner, WA, Lawson, WB, Nwulia, EA, Hipolito, M, Coryell, W, Rice, J, Byerley, W, Mcmahon, FJ, Schulze, TG, Berrettini, W, Lohoff, FW, Potash, JB, Mahon, PB, Mcinnis, MG, Zöllner, S, Zhang, P, Craig, DW, Szelinger, S, Barrett, TB, Breuer, R, Meier, S, Strohmaier, J, Witt, SH, Tozzi, F, Farmer, A, Mcguffin, P, Strauss, J, W., XU, Kennedy, JL, Vincent, JB, Matthews, K, Day, R, Ferreira, MA, O’dushlaine, C, Perlis, R, Raychaudhuri, S, Ruderfer, D, Lee, PH, Smoller, JW, Li, J, Absher, D, Bunney, WE, Barchas, JD, Schatzberg, AF, Jones, EG, Meng, F, Thompson, RC, Watson, SJ, Myers, RM, Akil, H, Boehnke, M, Chambert, K, Moran, J, Scolnick, E, Djurovic, S, Melle, I, Morken, G, Gill, M, Morris, D, Quinn, E, Mühleisen, TW, Degenhardt, FA, Mattheisen, M, et al. (2011) Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nature Genetics 43, 977–983.Google Scholar
Smith, GD and Ebrahim, S (2005) What can mendelian randomisation tell us about modifiable behavioural and environmental exposures? BMJ 330(7499), 1076–1079.CrossRefGoogle Scholar
Stahl, EA, Breen, G, Forstner, AJ, Mcquillin, A, Ripke, S, Trubetskoy, V, Mattheisen, M, Wang, Y, Coleman, JRI, Gaspar, HA, de Leeuw, CA, Steinberg, S, Pavlides, JMW, Trzaskowski, M, Byrne, EM, Pers, TH, Holmans, PA, Richards, AL, Abbott, L, Agerbo, E, Akil, H, Albani, D, Alliey-Rodriguez, N, T.D., ALS, Anjorin, A, Antilla, V, Awasthi, S, Badner, JA, Bækvad-Hansen, M, Barchas, JD, Bass, N, Bauer, M, Belliveau, R, Bergen, SE, Pedersen, CB, Bøen, E, Boks, MP, Boocock, J, Budde, M, Bunney, W, Burmeister, M, Bybjerg-Grauholm, J, Byerley, W, Casas, M, Cerrato, F, Cervantes, P, Chambert, K, Charney, AW, Chen, D, Churchhouse, C, Clarke, T-K, Coryell, W, Craig, DW, Cruceanu, C, Curtis, D, Czerski, PM, Dale, AM, de Jong, S, Degenhardt, F, Del-Favero, J, Depaulo, JR, Djurovic, S, Dobbyn, AL, Dumont, A, Elvsåshagen, T, Escott-Price, V, Fan, CC, Fischer, SB, Flickinger, M, Foroud, TM, Forty, L, Frank, J, Fraser, C, Freimer, NB, Frisén, L, Gade, K, Gage, D, Garnham, J, Giambartolomei, C, Pedersen, MG, Goldstein, J, Gordon, SD, Gordon-Smith, K, Green, EK, Green, MJ, Greenwood, TA, Grove, J, Guan, W, Guzman-Parra, J, Hamshere, ML, Hautzinger, M, Heilbronner, U, Herms, S, Hipolito, M, Hoffmann, P, Holland, D, Huckins, L, Jamain, S, Johnson, JS, Juréus, A, et al. (2019) Genome-wide association study identifies 30 loci associated with bipolar disorder. Nature Genetics 51, 793–803.CrossRefGoogle ScholarPubMed
Sun, BB, Maranville, JC, Peters, JE, Stacey, D, Staley, JR, Blackshaw, J, Burgess, S, Jiang, T, Paige, E, Surendran, P, Oliver-Williams, C, Kamat, MA, Prins, BP, Wilcox, SK, Zimmerman, ES, Chi, A, Bansal, N, Spain, SL, Wood, AM, Morrell, NW, Bradley, JR, Janjic, N, Roberts, DJ, Ouwehand, WH, Todd, JA, Soranzo, N, Suhre, K, Paul, DS, Fox, CS, Plenge, RM, Danesh, J, Runz, H and Butterworth, AS (2018) Genomic atlas of the human plasma proteome. Nature 558(7708), 73–79.CrossRefGoogle ScholarPubMed
van Battum, EY, Brignani, S and Pasterkamp, RJ (2015) Axon guidance proteins in neurological disorders. The Lancet Neurology 14(5), 532–546.CrossRefGoogle ScholarPubMed
Witt, SH, Juraeva, D, Sticht, C, Strohmaier, J, Meier, S, Treutlein, J, Dukal, H, Frank, J, Lang, M, Deuschle, M, Schulze, TG, Degenhardt, F, Mattheisen, M, Brors, B, Cichon, S, Nöthen, MM, Witt, CC, Rietschel, M (2014) Investigation of manic and euthymic episodes identifies state- and trait-specific gene expression and STAB1 as a new candidate gene for bipolar disorder. Translational Psychiatry 4(8), e426.CrossRefGoogle ScholarPubMed
Wolf, SS, Hyde, TM, Saunders, RC, Herman, MM, Weinberger, DR and Kleinman, JE (1995) Autoradiographic characterization of neurotensin receptors in the entorhinal cortex of schizophrenic patients and control subjects. Journal of Neural Transmission 102(1), 55–65.CrossRefGoogle ScholarPubMed
Yuji, Y, Madoka, M, Kazuki, I and Tomiki, S (2020) Specificity and continuity of schizophrenia and bipolar disorder: relation to biomarkers. Current Pharmaceutical Design 26(2), 191–200.Google Scholar
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