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Review Articles

Polygenic risk scores for predicting outcomes and treatment response in psychiatry: hope or hype?

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 663-675 | Received 26 May 2022, Accepted 08 Jul 2022, Published online: 27 Jul 2022

References

  • Alda, M. (2017). Who are excellent lithium responders and why do they matter? World Psychiatry, 16(3), 319–320. https://doi.org/10.1002/wps.20462
  • Amare, A. T., Schubert, K. O., Hou, L., Clark, S. R., Papiol, S., Cearns, M., Heilbronner, U., Degenhardt, F., Tekola-Ayele, F., Hsu, Y.-H., Shekhtman, T., Adli, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J.-M., Backlund, L., Bhattacharjee, A. K., … Baune, B. T. (2021). Association of polygenic score for major depression with response to lithium in patients with bipolar disorder. Molecular Psychiatry, 26(6), 2457–2470. https://doi.org/10.1038/s41380-020-0689-5
  • Amare, A. T., Schubert, K. O., Tekola-Ayele, F., Hsu, Y.-H., Sangkuhl, K., Jenkins, G., Whaley, R. M., Barman, P., Batzler, A., Altman, R. B., Arolt, V., Brockmöller, J., Chen, C.-H., Domschke, K., Hall-Flavin, D. K., Hong, C.-J., Illi, A., Ji, Y., Kampman, O., … Baune, B. T. (2018). Association of the polygenic scores for personality traits and response to selective serotonin reuptake inhibitors in patients with major depressive disorder. Frontiers in Psychiatry, 9, 65. https://doi.org/10.3389/fpsyt.2018.00065
  • Amare, A. T., Schubert, K. O., Tekola-Ayele, F., Hsu, Y.-H., Sangkuhl, K., Jenkins, G., Whaley, R. M., Barman, P., Batzler, A., Altman, R. B., Arolt, V., Brockmöller, J., Chen, C.-H., Domschke, K., Hall-Flavin, D. K., Hong, C.-J., Illi, A., Ji, Y., Kampman, O., … Baune, B. T. (2019). The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression. Journal of Neural Transmission, 126(1), 35–45. https://doi.org/10.1007/s00702-018-01966-x
  • Belbin, G. M., Cullina, S., Wenric, S., Soper, E. R., Glicksberg, B. S., Torre, D., Moscati, A., Wojcik, G. L., Shemirani, R., Beckmann, N. D., Cohain, A., Sorokin, E. P., Park, D. S., Ambite, J.-L., Ellis, S., Auton, A., Bottinger, E. P., Cho, J. H., Loos, R. J. F., … Kenny, E. E. (2021). Toward a fine-scale population health monitoring system. Cell, 184(8), 2068–2083. https://doi.org/10.1016/j.cell.2021.03.034
  • Burkhard, C., Cicek, S., Barzilay, R., Radhakrishnan, R., & Guloksuz, S. (2021). Need for ethnic and population diversity in psychosis research. Schizophrenia Bulletin, 47(4), 889–895. https://doi.org/10.1093/schbul/sbab048
  • Cearns, M., Amare, A. T., Schubert, K. O., Thalamuthu, A., Frank, J., Streit, F., Adli, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J.-M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., … Baune, B. T. (2022). Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: Machine learning approach. British Journal of Psychiatry. Advance online publication. https://doi.org/10.1192/bjp.2022.28
  • Choi, S. W., Mak, T. S.-H., & O’Reilly, P. F. (2020). Tutorial: A guide to performing polygenic risk score analyses. Nature Protocols, 15(9), 2759–2772. https://doi.org/10.1038/s41596-020-0353-1
  • Dewey, F. E., Grove, M. E., Pan, C., Goldstein, B. A., Bernstein, J. A., Chaib, H., Merker, J. D., Goldfeder, R. L., Enns, G. M., David, S. P., Pakdaman, N., Ormond, K. E., Caleshu, C., Kingham, K., Klein, T. E., Whirl-Carrillo, M., Sakamoto, K., Wheeler, M. T., Butte, A. J., … Quertermous, T. (2014). Clinical interpretation and implications of whole-genome sequencing. JAMA, 311(10), 1035–1045. https://doi.org/10.1001/jama.2014.1717
  • Erzin, G., Pries, L.-K., Dimitrakopoulos, S., Ralli, I., Xenaki, L.-A., Soldatos, R.-F., Vlachos, I., Selakovic, M., Foteli, S., Kosteletos, I., Nianiakas, N., Mantonakis, L., Rizos, E., Kollias, K., Van Os, J., Guloksuz, S., & Stefanis, N. (2021). Association between exposome score for schizophrenia and functioning in first-episode psychosis: Results from the Athens first-episode psychosis research study. Psychological Medicine. Avance online publication. https://doi.org/10.1017/S0033291721004542
  • Erzin, G., Pries, L.-K., van Os, J., Fusar-Poli, L., Delespaul, P., Kenis, G., Luykx, J. J., Lin, B. D., Richards, A. L., Akdede, B., Binbay, T., Altınyazar, V., Yalınçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Cankurtaran, E. Ş., Kaymak, S. U., … Guloksuz, S. (2021). Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study. European Psychiatry, 64(1), e25. https://doi.org/10.1192/j.eurpsy.2021.19
  • Fabbri, C., Hagenaars, S. P., John, C., Williams, A. T., Shrine, N., Moles, L., Hanscombe, K. B., Serretti, A., Shepherd, D. J., Free, R. C., Wain, L. V., Tobin, M. D., & Lewis, C. M. (2021). Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts. Molecular Psychiatry, 26(7), 3363–3373. https://doi.org/10.1038/s41380-021-01062-9
  • Fanelli, G., Benedetti, F., Kasper, S., Zohar, J., Souery, D., Montgomery, S., Albani, D., Forloni, G., Ferentinos, P., Rujescu, D., Mendlewicz, J., Serreti A., & Fabbri, C. (2021). Higher polygenic risk scores for schizophrenia may be suggestive of treatment non-response in major depressive disorder. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 108, 110170. https://doi.org/10.1016/j.pnpbp.2020.110170
  • Fanelli, G., Domschke, K., Minelli, A., Gennarelli, M., Martini, P., Bortolomasi, M., Maron, E., Squassina, A., Kasper, S., Zohar, J., Souery, D., Montgomery, S., Albani, D., Forloni, G., Ferentinos, P., Rujescu, D., Mendlewicz, J., De Ronchi, D., Baune, B. T., Serretti, A., … Fabbri, C. (2022). A meta-analysis of polygenic risk scores for mood disorders, neuroticism, and schizophrenia in antidepressant response. European Neuropsychopharmacology, 55, 86–95. https://doi.org/10.1016/j.euroneuro.2021.11.005
  • Ferrara, M., & Srihari, V. H. (2021). Early intervention for psychosis in the United States: Tailoring services to improve care for women. Psychiatric Services, 72(1), 5–6. https://doi.org/10.1176/appi.ps.202000205
  • Foo, J. C., Streit, F., Frank, J., Witt, S. H., Treutlein, J., Baune, B. T., Moebus, S., Jöckel, K.-H., Forstner, A. J., Nöthen, M. M., Rietschel, M., Sartorius, A., & Kranaster, L. (2019). Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 180(1), 35–45. https://doi.org/10.1002/ajmg.b.32700
  • Frank, J., Lang, M., Witt, S. H., Strohmaier, J., Rujescu, D., Cichon, S., Degenhardt, F., Nöthen, M. M., Collier, D. A., Ripke, S., Naber, D., & Rietschel, M. (2015). Identification of increased genetic risk scores for schizophrenia in treatment-resistant patients. Molecular Psychiatry, 20(2), 150–151. https://doi.org/10.1038/mp.2014.56
  • García-González, J., Tansey, K. E., Hauser, J., Henigsberg, N., Maier, W., Mors, O., Placentino, A., Rietschel, M., Souery, D., Žagar, T., Czerski, P. M., Jerman, B., Buttenschøn, H. N., Schulze, T. G., Zobel, A., Farmer, A., Aitchison, K. J., Craig, I., McGuffin, P., … Fabbri, C. (2017). Pharmacogenetics of antidepressant response: A polygenic approach. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 75, 128–134. https://doi.org/10.1016/j.pnpbp.2017.01.011
  • Gibson, G. (2019). On the utilization of polygenic risk scores for therapeutic targeting. PLoS Genetics, 15(4), e1008060. https://doi.org/10.1371/journal.pgen.1008060
  • Girgus, J. S., & Yang, K. (2015). Gender and depression. Current Opinion in Psychology, 4, 53–60. https://doi.org/10.1016/j.copsyc.2015.01.019
  • Gottesman, I. I., & Shields, J. (1967). A polygenic theory of schizophrenia. Proceedings of the National Academy of Sciences, 58(1), 199–205. https://doi.org/10.1073/pnas.58.1.199
  • Guloksuz, S., & van Os, J. (2018). The slow death of the concept of schizophrenia and the painful birth of the psychosis spectrum. Psychological Medicine, 48(2), 229–244. https://doi.org/10.1017/S0033291717001775
  • Guloksuz, S., & van Os, J. (2020). Dr. Strangelove, or how we learned to stop worrying and love uncertainty. World Psychiatry, 19(3), 395–396. https://doi.org/10.1002/wps.20794
  • Guloksuz, S., Pries, L.-K., Ten Have, M., de Graaf, R., van Dorsselaer, S., Klingenberg, B., Bak, M., Lin, B. D., van Eijk, K. R., Delespaul, P., van Amelsvoort, T., Luykx, J. J., Rutten, B. P. F., & van Os, J. (2020). Association of preceding psychosis risk states and non-psychotic mental disorders with incidence of clinical psychosis in the general population: A prospective study in the NEMESIS-2 cohort. World Psychiatry, 19(2), 199–205. https://doi.org/10.1002/wps.20755
  • Guloksuz, S., Rutten, B. P. F., Pries, L.-K., Ten Have, M., de Graaf, R., van Dorsselaer, S., Klingenberg, B., van Os, J., & Ioannidis, J. P. A. (2018). The complexities of evaluating the exposome in psychiatry: A data-driven illustration of challenges and some propositions for amendments. Schizophrenia Bulletin, 44(6), 1175–1179. https://doi.org/10.1093/schbul/sby118
  • Guloksuz, S., van Os, J., & Rutten, B. P. F. (2018). The exposome paradigm and the complexities of environmental research in psychiatry. JAMA Psychiatry, 75(10), 985–986. https://doi.org/10.1001/jamapsychiatry.2018.1211
  • Haq, A. U., Sitzmann, A. F., Goldman, M. L., Maixner, D. F., & Mickey, B. J. (2015). Response of depression to electroconvulsive therapy: A meta-analysis of clinical predictors. The Journal of Clinical Psychiatry, 76(10), 1374–1384. https://doi.org/10.4088/JCP.14r09528
  • Harrow, M., Grossman, L. S., Jobe, T. H., & Herbener, E. S. (2005). Do patients with schizophrenia ever show periods of recovery? A 15-year multi-follow-up study. Schizophrenia Bulletin, 31(3), 723–734. https://doi.org/10.1093/schbul/sbi026
  • Hilker, R., Helenius, D., Fagerlund, B., Skytthe, A., Christensen, K., Werge, T. M., Nordentoft, M., & Glenthøj, B. (2018). Heritability of schizophrenia and schizophrenia spectrum based on the nationwide Danish Twin Register. Biological Psychiatry, 83(6), 492–498. https://doi.org/10.1016/j.biopsych.2017.08.017
  • Howard, D. M., Adams, M. J., Clarke, T.-K., Hafferty, J. D., Gibson, J., Shirali, M., Coleman, J. R. I., Hagenaars, S. P., Ward, J., Wigmore, E. M., Alloza, C., Shen, X., Barbu, M. C., Xu, E. Y., Whalley, H. C., Marioni, R. E., Porteous, D. J., Davies, G., Deary, I. J., … McIntosh, A. M. (2019). Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nature Neuroscience, 22(3), 343–352. https://doi.org/10.1038/s41593-018-0326-7
  • Ioannidis, J. P. (2005). Why most published research findings are false. PLoS Medicine, 2(8), e124. https://doi.org/10.1371/journal.pmed.0020124
  • Ioannidis, J. P. (2008). Why most discovered true associations are inflated. Epidemiology, 19(5), 640–648. https://doi.org/10.1097/EDE.0b013e31818131e7
  • Janssens, A. C. J. W. (2019). Validity of polygenic risk scores: Are we measuring what we think we are? Human Molecular Genetics, 28(R2), R143–R150. https://doi.org/10.1093/hmg/ddz205
  • Jonas, K. G., Lencz, T., Li, K., Malhotra, A. K., Perlman, G., Fochtmann, L. J., Bromet, E. J., & Kotov, R. (2019). Schizophrenia polygenic risk score and 20-year course of illness in psychotic disorders. Translational Psychiatry, 9(1), 300. https://doi.org/10.1038/s41398-019-0612-5
  • Jones, H. J., Stergiakouli, E., Tansey, K. E., Hubbard, L., Heron, J., Cannon, M., Holmans, P., Lewis, G., Linden, D. E. J., Jones, P. B., Davey Smith, G., O’Donovan, M. C., Owen, M. J., Walters, J. T., & Zammit, S. (2016). Phenotypic manifestation of genetic risk for schizophrenia during adolescence in the general population. JAMA Psychiatry, 73(3), 221–228. https://doi.org/10.1001/jamapsychiatry.2015.3058
  • Landi, I., Kaji, D. A., Cotter, L., Van Vleck, T., Belbin, G., Preuss, M., Loos, R. J. F., Kenny, E., Glicksberg, B. S., Beckmann, N. D., O’Reilly, P., Schadt, E. E., Achtyes, E. D., Buckley, P. F., Lehrer, D., Malaspina, D. P., McCarroll, S. A., Rapaport, M. H., Fanous, A. H., … Charney, A. W. (2021). Prognostic value of polygenic risk scores for adults with psychosis. Nature Medicine, 27(9), 1576–1581. https://doi.org/10.1038/s41591-021-01475-7
  • Lewis, C. M., & Vassos, E. (2020). Polygenic risk scores: From research tools to clinical instruments. Genome Medicine, 12(1), 44. https://doi.org/10.1186/s13073-020-00742-5
  • Li, Q. S., Wajs, E., Ochs-Ross, R., Singh, J., & Drevets, W. C. (2020). Genome-wide association study and polygenic risk score analysis of esketamine treatment response. Scientific Reports, 10(1), 12649. https://doi.org/10.1038/s41598-020-69291-6
  • Luykx, J. J., Loef, D., Lin, B., van Diermen, L., Nuninga, J. O., van Exel, E., Oudega, M. L., Rhebergen, D., Schouws, S. N., van Eijndhoven, P., Verwijk, E., Schrijvers, D., Birkenhager, T. K., Ryan, K. M., Arts, B., van Bronswijk, S. C., Kenis, G., Schurgers, G., Baune, B. T., … Rutten, B. P. (2022). Interrogating associations between polygenic liabilities and electroconvulsive therapy effectiveness. Biological Psychiatry, 91(6), 531–539. https://doi.org/10.1016/j.biopsych.2021.10.013
  • Maj, M., Stein, D. J., Parker, G., Zimmerman, M., Fava, G. A., De Hert, M., Demyttenaere, K., McIntyre, R. S., Widiger, T., & Wittchen, H.-U. (2020). The clinical characterization of the adult patient with depression aimed at personalization of management. World Psychiatry, 19(3), 269–293. https://doi.org/10.1002/wps.20771
  • Marshe, V. S., Maciukiewicz, M., Hauschild, A.-C., Islam, F., Qin, L., Tiwari, A. K., Sibille, E., Blumberger, D. M., Karp, J. F., Flint, A. J., Turecki, G., Lam, R. W., Milev, R. V., Frey, B. N., Rotzinger, S., Foster, J. A., Kennedy, S. H., Kennedy, J. L., Mulsant, B. H., … Müller, D. J. (2021). Genome-wide analysis suggests the importance of vascular processes and neuroinflammation in late-life antidepressant response. Translational Psychiatry, 11(1), 127. https://doi.org/10.1038/s41398-021-01248-3
  • McIntyre, R. S., Filteau, M.-J., Martin, L., Patry, S., Carvalho, A., Cha, D. S., Barakat, M., & Miguelez, M. (2014). Treatment-resistant depression: Definitions, review of the evidence, and algorithmic approach. Journal of Affective Disorders, 156, 1–7. https://doi.org/10.1016/j.jad.2013.10.043
  • Meerman, J. J., ter Hark, S. E., Janzing, J. G. E., & Coenen, M. J. H. (2022). The potential of polygenic risk scores to predict antidepressant treatment response in major depression: A systematic review. Journal of Affective Disorders, 304, 1–11. https://doi.org/10.1016/j.jad.2022.02.015
  • Mistry, S., Escott-Price, V., Florio, A. D., Smith, D. J., & Zammit, S. (2019). Investigating associations between genetic risk for bipolar disorder and cognitive functioning in childhood. Journal of Affective Disorders, 259, 112–120. https://doi.org/10.1016/j.jad.2019.08.040
  • Murray, G. K., Lin, T., Austin, J., McGrath, J. J., Hickie, I. B., & Wray, N. R. (2021). Could polygenic risk scores be useful in psychiatry? A review. JAMA Psychiatry, 78(2), 210–219. https://doi.org/10.1001/jamapsychiatry.2020.3042
  • Pain, O., Dudbridge, F., Cardno, A. G., Freeman, D., Lu, Y., Lundstrom, S., Lichtenstein, P., & Ronald, A. (2018). Genome‐wide analysis of adolescent psychotic‐like experiences shows genetic overlap with psychiatric disorders. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 177(4), 416–425. https://doi.org/10.1002/ajmg.b.32630
  • Pardiñas, A. F., Smart, S. E., Willcocks, I. R., Holmans, P. A., Dennison, C. A., Lynham, A. J., Legge, S. E., Baune, B. T., Bigdeli, T. B., Cairns, M. J., Corvin, A., Fanous, A. H., Frank, J., Kelly, B., McQuillin, A., Melle, I., Mortensen, P. B., Mowry, B. J., Pato, C. N., … Vázquez-Bourgon, J. (2022). Interaction testing and polygenic risk scoring to estimate the association of common genetic variants with treatment resistance in schizophrenia. JAMA Psychiatry, 79(3), 260–269. https://doi.org/10.1001/jamapsychiatry.2021.3799
  • Parker, G., & Brotchie, H. (2010). Gender differences in depression. International Review of Psychiatry, 22(5), 429–436. https://doi.org/10.3109/09540261.2010.492391
  • Pato, M. T., Sobell, J. L., Medeiros, H., Abbott, C., Sklar, B. M., Buckley, P. F., Bromet, E. J., Escamilla, M. A., Fanous, A. H., Lehrer, D. S., Macciardi, F., Malaspina, D., McCarroll, S. A., Marder, S. R., Moran, J., Morley, C. P., Nicolini, H., Perkins, D. O., Purcell, S. M., … Pato, C. N. (2013). The genomic psychiatry cohort: Partners in discovery. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 162(4), 306–312. https://doi.org/10.1002/ajmg.b.32160
  • Pence, A. Y., Pries, L. K., Ferrara, M., Rutten, B. P. F., van Os, J., & Guloksuz, S. (2022). Gender differences in the association between environment and psychosis. Schizophrenia Research, 243, 120–137. https://doi.org/10.1016/j.schres.2022.02.039
  • Popejoy, A. B., & Fullerton, S. M. (2016). Genomics is failing on diversity. Nature, 538(7624), 161–164. https://doi.org/10.1038/538161a
  • Pries, L.-K., Dal Ferro, G. A., van Os, J., Delespaul, P., Kenis, G., Lin, B. D., Luykx, J. J., Richards, A. L., Akdede, B., Binbay, T., Altınyazar, V., Yalınçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Şahin Cankurtaran, E., Ulusoy Kaymak, S., Mihaljevic, M. M., … Guloksuz, S. (2020). Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum. Epidemiology and Psychiatric Sciences, 29, e182. https://doi.org/10.1017/S2045796020000943
  • Pries, L.-K., Erzin, G., van Os, J., ten Have, M., de Graaf, R., van Dorsselaer, S., Bak, M., Rutten, B. P. F., & Guloksuz, S. (2021). Predictive performance of exposome score for schizophrenia in the general population. Schizophrenia Bulletin, 47(2), 277–283. https://doi.org/10.1093/schbul/sbaa170
  • Pries, L.-K., Lage-Castellanos, A., Delespaul, P., Kenis, G., Luykx, J. J., Lin, B. D., Richards, A. L., Akdede, B., Binbay, T., Altinyazar, V., Yalinçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Cankurtaran, E. Ş., Kaymak, S. U., Mihaljevic, M. M., Petrovic, S. A., … Guloksuz, S. (2019). Estimating exposome score for schizophrenia using predictive modeling approach in two independent samples: The results from the EUGEI Study. Schizophrenia Bulletin, 45(5), 960–965. https://doi.org/10.1093/schbul/sbz054
  • Pries, L.-K., van Os, J., Ten Have, M., de Graaf, R., van Dorsselaer, S., Bak, M., Lin, B. D., van Eijk, K. R., Kenis, G., Richards, A., O’Donovan, M. C., Luykx, J. J., Rutten, B. P. F., & Guloksuz, S. (2020). Association of recent stressful life events with mental and physical health in the context of genomic and exposomic liability for schizophrenia. JAMA Psychiatry, 77(12), 1296–1304. https://doi.org/10.1001/jamapsychiatry.2020.2304
  • Reich, D. E., & Lander, E. S. (2001). On the allelic spectrum of human disease. Trends in Genetics, 17(9), 502–510. https://doi.org/10.1016/S0168-9525(01)02410-6
  • Ruderfer, D. M., Charney, A. W., Readhead, B., Kidd, B. A., Kähler, A. K., Kenny, P. J., Keiser, M. J., Moran, J. L., Hultman, C. M., Scott, S. A., Sullivan, P. F., Purcell, S. M., Dudley, J. T., & Sklar, P. (2016). Polygenic overlap between schizophrenia risk and antipsychotic response: A genomic medicine approach. The Lancet. Psychiatry, 3(4), 350–357. https://doi.org/10.1016/S2215-0366(15)00553-2
  • Schubert, K. O., Thalamuthu, A., Amare, A. T., Frank, J., Streit, F., Adl, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J.-M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Marie-Claire, C., … Baune, B. T. (2021). Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients. Translational Psychiatry, 11(1), 606. https://doi.org/10.1038/s41398-021-01702-2
  • Shah, J. L., Jones, N., van Os, J., McGorry, P. D., & Gülöksüz, S. (2022). Early intervention service systems for youth mental health: Integrating pluripotentiality, clinical staging, and transdiagnostic lessons from early psychosis. The Lancet. Psychiatry, 9(5), 413–422. https://doi.org/10.1016/S2215-0366(21)00467-3
  • Singh, T., Poterba, T., Curtis, D., Akil, H., Al Eissa, M., Barchas, J. D., Bass, N., Bigdeli, T. B., Breen, G., Bromet, E. J., Buckley, P. F., Bunney, W. E., Bybjerg-Grauholm, J., Byerley, W. F., Chapman, S. B., Chen, W. J., Churchhouse, C., Craddock, N., Cusick, C. M., … Daly, M. J. (2022). Rare coding variants in ten genes confer substantial risk for schizophrenia. Nature, 604(7906), 509–516. https://doi.org/10.1038/s41586-022-04556-w
  • Smoller, J. W., Andreassen, O. A., Edenberg, H. J., Faraone, S. V., Glatt, S. J., & Kendler, K. S. (2019). Psychiatric genetics and the structure of psychopathology. Molecular Psychiatry, 24(3), 409–420. https://doi.org/10.1038/s41380-017-0010-4
  • Suwinski, P., Ong, C., Ling, M. H., Poh, Y. M., Khan, A. M., & Ong, H. S. (2019). Advancing personalized medicine through the application of whole exome sequencing and big data analytics. Frontiers in Genetics, 10, 49. https://doi.org/10.3389/fgene.2019.00049
  • Tansey, K. E., Guipponi, M., Domenici, E., Lewis, G., Malafosse, A., O’Donovan, M., Wendland, J. R., Lewis, C. M., McGuffin, P., & Uher, R. (2014). Genetic susceptibility for bipolar disorder and response to antidepressants in major depressive disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 165(1), 77–83. https://doi.org/10.1002/ajmg.b.32210
  • Trubetskoy, V., Pardiñas, A. F., Qi, T., Panagiotaropoulou, G., Awasthi, S., Bigdeli, T. B., Bryois, J., Chen, C.-Y., Dennison, C. A., Hall, L. S., Lam, M., Watanabe, K., Frei, O., Ge, T., Harwood, J. C., Koopmans, F., Magnusson, S., Richards, A. L., Sidorenko, J., … van Os, J. (2022). Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature, 604(7906), 502–508. https://doi.org/10.1038/s41586-022-04434-5
  • van Diermen, L., van den Ameele, S., Kamperman, A. M., Sabbe, B. C. G., Vermeulen, T., Schrijvers, D., & Birkenhäger, T. K. (2018). Prediction of electroconvulsive therapy response and remission in major depression: Meta-analysis. The British Journal of Psychiatry, 212(2), 71–80. https://doi.org/10.1192/bjp.2017.28
  • van Os, J., Kenis, G., & Rutten, B. P. (2010). The environment and schizophrenia. Nature, 468(7321), 203–212. https://doi.org/10.1038/nature09563
  • Wagner, E., Siafis, S., Fernando, P., Falkai, P., Honer, W. G., Röh, A., Siskind, D., Leucht, S., & Hasan, A. (2021). Efficacy and safety of clozapine in psychotic disorders—a systematic quantitative meta-review. Translational Psychiatry, 11(1), 1–18. https://doi.org/10.1038/s41398-021-01613-2
  • Wand, H., Lambert, S. A., Tamburro, C., Iacocca, M. A., O’Sullivan, J. W., Sillari, C., Kullo, I. J., Rowley, R., Dron, J. S., Brockman, D., Venner, E., McCarthy, M. I., Antoniou, A. C., Easton, D. F., Hegele, R. A., Khera, A. V., Chatterjee, N., Kooperberg, C., Edwards, K., … Wojcik, G. L. (2021). Improving reporting standards for polygenic scores in risk prediction studies. Nature, 591(7849), 211–219. https://doi.org/10.1038/s41586-021-03243-6
  • Ward, J., Graham, N., Strawbridge, R. J., Ferguson, A., Jenkins, G., Chen, W., Hodgson, K., Frye, M., Weinshilboum, R., Uher, R., Lewis, C. M., Biernacka, J., & Smith, D. J. (2018). Polygenic risk scores for major depressive disorder and neuroticism as predictors of antidepressant response: Meta-analysis of three treatment cohorts. PLoS One, 13(9), e0203896. https://doi.org/10.1371/journal.pone.0203896
  • Werner, M. C. F., Wirgenes, K. V., Haram, M., Bettella, F., Lunding, S. H., Rødevand, L., Hjell, G., Agartz, I., Djurovic, S., Melle, I., Andreassen, O. A., & Steen, N. E. (2020). Indicated association between polygenic risk score and treatment-resistance in a naturalistic sample of patients with schizophrenia spectrum disorders. Schizophrenia Research, 218, 55–62. https://doi.org/10.1016/j.schres.2020.03.006
  • Wigmore, E. M., Hafferty, J. D., Hall, L. S., Howard, D. M., Clarke, T.-K., Fabbri, C., Lewis, C. M., Uher, R., Navrady, L. B., Adams, M. J., Zeng, Y., Campbell, A., Gibson, J., Thomson, P. A., Hayward, C., Smith, B. H., Hocking, L. J., Padmanabhan, S., Deary, I. J., … McIntosh, A. M. (2020). Genome-wide association study of antidepressant treatment resistance in a population-based cohort using health service prescription data and meta-analysis with GENDEP. The Pharmacogenomics Journal, 20(2), 329–341. https://doi.org/10.1038/s41397-019-0067-3
  • Wild, C. P. (2005). Complementing the genome with an “exposome”: The outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiology, Biomarkers & Prevention, 14(8), 1847–1850. https://doi.org/10.1158/1055-9965.EPI-05-0456
  • Wild, C. P. (2012). The exposome: From concept to utility. International Journal of Epidemiology, 41(1), 24–32. https://doi.org/10.1093/ije/dyr236
  • Wimberley, T., Gasse, C., Meier, S. M., Agerbo, E., MacCabe, J. H., & Horsdal, H. T. (2017). Polygenic risk score for schizophrenia and treatment-resistant schizophrenia. Schizophrenia Bulletin, 43(5), 1064–1069. https://doi.org/10.1093/schbul/sbx007
  • Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., Sharma, V., Goldstein, B. I., Rej, S., Beaulieu, S., Alda, M., MacQueen, G., Milev, R. V., Ravindran, A., O’Donovan, C., McIntosh, D., Lam, R. W., Vazquez, G., Kapczinski, F., … Berk, M. (2018). Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disorders, 20(2), 97–170. https://doi.org/10.1111/bdi.12609
  • Zhang, J. P., & Malhotra, A. K. (2018). Recent progress in pharmacogenomics of antipsychotic drug response. Current Psychiatry Reports, 20(4), 24. https://doi.org/10.1007/s11920-018-0886-y
  • Zhang, J.-P., Robinson, D., Yu, J., Gallego, J., Fleischhacker, W. W., Kahn, R. S., Crespo-Facorro, B., Vazquez-Bourgon, J., Kane, J. M., Malhotra, A. K., & Lencz, T. (2019). Schizophrenia polygenic risk score as a predictor of antipsychotic efficacy in first-episode psychosis. American Journal of Psychiatry, 176(1), 21–28. https://doi.org/10.1176/appi.ajp.2018.17121363