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Chapter 17 - Genetics of Mood Disorders

Published online by Cambridge University Press:  16 May 2024

By
Camila Nayane de Carvalho Lima ,
Christopher Busby  and
Gabriel Rodrigo Fries
Edited by
Allan Young ,
Marsal Sanches ,
Jair C. Soares  and
Mario Juruena
Allan Young
Affiliation:
Institute of Psychiatry, King's College London
Marsal Sanches
Affiliation:
Baylor College of Medicine, Texas
Jair C. Soares
Affiliation:
McGovern Medical School, The University of Texas
Mario Juruena
Affiliation:
King's College London
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Summary

Mood disorders, including bipolar disorder (BD) and major depressive disorder (MDD), are known to have a significant genetic component based on familial and twin studies. Tremendous efforts from the scientific community and technical advancements have led to the discovery of multiple genes associated with the heritability of these disorders over the last years. Nonetheless, our knowledge of the exact genetic basis of BD and MDD is still fairly limited. Recent genome-wide association studies with massive sample sizes have started to characterize the polygenicity of these disorders, although future studies have yet to explore how genetic variants may interact with the environment to modulate one’s risk of disease. As our understanding of the genetics of mood disorders increases (with increasing sample sizes, a more significant shift from candidate gene studies to microarray and sequencing strategies, and integration of findings with environmental measures), many clinical opportunities may arise. This may include the future use of polygenic risk scores for risk assessment, predicting response to medications based on genotype, among others.

Keywords

mood disordersbipolar disordermajor depressive disordergeneticsGWASepigenetics
Type
Chapter
Information
Clinical Textbook of Mood Disorders , pp. 172 - 177
Publisher: Cambridge University Press
Print publication year: 2024

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References

Bauer, M., Pfennig, A.. Epidemiology of bipolar disorders. Epilepsia 2005;46:8–13.CrossRefGoogle ScholarPubMed
Demyttenaere, K., Bruffaerts, R., Posada-Villa, J., et al. Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys. JAMA 2004;291:2581–90.Google ScholarPubMed
Levinson, D.F.. The genetics of depression: a review. Biol Psychiatry 2006;60:84–92.CrossRefGoogle ScholarPubMed
McGuffin, P., Rijsdijk, F., Andrew, M., et al. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry 2003;60:497–502.CrossRefGoogle ScholarPubMed
Berrettini, W.H.. Molecular linkage studies of bipolar disorder. Dialogues Clin Neurosci 1999;1:12–21.CrossRefGoogle ScholarPubMed
McMahon, F.J., Hopkins, P.J, Xu, J., et al. Linkage of bipolar affective disorder to chromosome 18 markers in a new pedigree series. Am J Hum Genet 1997;61:1397–1404.CrossRefGoogle Scholar
Turecki, G., Grof, P., Cavazzoni, P., et al. Lithium responsive bipolar disorder, unilineality, and chromosome 18: a linkage study. Am J Med Genet 1999;88:411–15.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Craddock, N., Davé, S., Greening, J.. Association studies of bipolar disorder. Bipolar Disorders 2001;3:284–98.CrossRefGoogle ScholarPubMed
Gordovez, F.J.A., McMahon, F.J.. The genetics of bipolar disorder. Molecular Psychiatry 2020;25:544–59.CrossRefGoogle ScholarPubMed
Charney, A.W., Ruderfer, D.M, Stahl, E.A, et al. Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder. Transl Psychiatry 2017;7:e993.CrossRefGoogle ScholarPubMed
O’Connell, K.S., Coombes, B.J.. Genetic contributions to bipolar disorder: current status and future directions. Psycol Med 2021;51:2156–67.Google ScholarPubMed
Burton, P.R., Clayton, D.G., Cardon, L.R., et al. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007;447:661–78.Google Scholar
Chen, D.T., Jiang, X., Akula, N., et al. Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder. Mol Psychiatry 2013;18:195–205.CrossRefGoogle ScholarPubMed
Hou, L., Bergen, S.E., Akula, N., et al. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder. Hum Mol Genet 2016;25:3383–94.CrossRefGoogle ScholarPubMed
Stahl, E.A., Breen, G., Forstner, A.J., et al. Genome-wide association study identifies 30 loci associated with bipolar disorder. Nat Genet 2019;51:793–803.CrossRefGoogle ScholarPubMed
Mullins, N., Forstner, A.J., O’Connell, K.S., et al. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nat Genet. 2021;53(6):817–29.CrossRefGoogle ScholarPubMed
Jiang, X., Detera-Wadleigh, S.D., Akula, N., et al. Sodium valproate rescues expression of TRANK1 in iPSC-derived neural cells that carry a genetic variant associated with serious mental illness. Mol Psychiatry 2019;24:613–24.CrossRefGoogle ScholarPubMed
Lai, J., Jiang, J., Zhang, P., et al. Impaired blood‐brain barrier in the microbiota‐gut‐brain axis: Potential role of bipolar susceptibility gene TRANK1. J Cell Mol Med 2021;00:jcmm.16611.Google Scholar
Jiang, X., Detera-Wadleigh, S.D., Akula, N., et al. Sodium valproate rescues expression of TRANK1 in iPSC-derived neural cells that carry a genetic variant associated with serious mental illness. Mol Psychiatry 2019;24:613–24.CrossRefGoogle ScholarPubMed
Baum, A.E., Akula, N., Cabanero, M., et al. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 2008;13:197–207.CrossRefGoogle ScholarPubMed
Kordeli, E., Lambert, S., Bennett., V. Ankyrin(G). A new ankyrin gene with neural-specific isoforms localized at the axonal initial segment and node of Ranvier. J Biol Chem 1995;270:2352–9.Google ScholarPubMed
Maheshwari, M., Shi, J., Badner, J.A. et al. Common and rare variants of DAOA in bipolar disorder. Am J Med Genet Part B Neuropsychiatr Genet 2009;150:960–966.CrossRefGoogle Scholar
Gershon, E.S., Grennan, K., Busnello, J., et al. A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene expression associated with a bipolar-associated common SNP of CACNA1C in brain. Mol Psychiatry 2014;19:890–894.CrossRefGoogle Scholar
Sklar, P., Ripke, S., Scott, L.J., et al. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 2011;43:977–85.Google Scholar
Heinrich, A., Lourdusamy, A., Tzschoppe, J., et al. The risk variant in ODZ4 for bipolar disorder impacts on amygdala activation during reward processing. Bipolar Disord 2013;15:440–5.CrossRefGoogle ScholarPubMed
Sklar, P., Ripke, S., Scott, L.J., et al. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 2011;43:977–85.Google Scholar
Purcell, S.M., Wray, N.R., Stone, J.L., et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009;460:748–52.Google ScholarPubMed
Ruderfer, D.M., Fanous, A.H., Ripke, S., et al. Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia. Mol Psychiatry 2014;19:1017–24.CrossRefGoogle Scholar
Stahl, E.A., Breen, G., Forstner, A.J., et al. Genome-wide association study identifies 30 loci associated with bipolar disorder. Nat Genet 2019;51:793–803.CrossRefGoogle ScholarPubMed
Middeldorp, C.M., De Moor, M.H.M., McGrath, L.M., et al. The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data. Transl Psychiatry 2011;1:e50.CrossRefGoogle ScholarPubMed
Huang, J., Perlis, R.H., Lee, P.H., et al. Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression. Am J Psychiatry 2010;167:1254–63.CrossRefGoogle ScholarPubMed
Weber, H., Kittel-Schneider, S., Gessner, A., et al. Cross-disorder analysis of bipolar risk genes: further evidence of dGKH as a risk gene for bipolar disorder, but also unipolar depression and adult ADHD. Neuropsychopharmacology 2011;36:2076–85.CrossRefGoogle ScholarPubMed
O’Brien, H.E., Hannon, E., Hill, M.J., et al. Expression quantitative trait loci in the developing human brain and their enrichment in neuropsychiatric disorders. Genome Biol 2018;19:194.CrossRefGoogle ScholarPubMed
Witt, S.H., Streit, F., Jungkunz, M., et al. Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia. Transl Psychiatry 2017;7:e1155.CrossRefGoogle ScholarPubMed
Power, R.A., Steinberg, S., Bjornsdottir, G., et al. Polygenic risk scores for schizophrenia and bipolar disorder predict creativity. Nat Neurosci 2015;18:953–5.CrossRefGoogle ScholarPubMed
Kyaga, S., Lichtenstein, P., Boman, M., et al. Bipolar disorder and leadership – a total population study. Acta Psychiatr Scand 2015;131:111–19.CrossRefGoogle ScholarPubMed
Lieb, R., Isensee, B., Höfler, M., et al. Parental major depression and the risk of depression and other mental disorders in offspring: a prospective-longitudinal community study. Arch Gen Psychiatry 2002;59:365–74.CrossRefGoogle ScholarPubMed
Sullivan, P.F., Neale, M.C., Kendler, K.S.. Genetic epidemiology of major depression: Review and meta-analysis. Am J Psychiatry 2000;157:1552–62.CrossRefGoogle ScholarPubMed
Mullins, N., Lewis, C.M.. Genetics of depression: progress at last. Curr Psychiatry Rep 2017;19:43.CrossRefGoogle ScholarPubMed
McIntosh, A.M., Sullivan, P.F., Lewis, C.M.. Uncovering the genetic architecture of major depression. Neuron 2019;102:91–103.CrossRefGoogle ScholarPubMed
Border, R., Johnson, E.C., Evans, L.M., et al. No support for historical candidate gene or candidate gene-by-interaction hypotheses for major depression across multiple large samples. Am J Psychiatry 2019;176:376–87.CrossRefGoogle ScholarPubMed
Unal-Aydin, P., Aydin, O., Arslan, A.. Genetic architecture of depression: where do we stand now? Adv Exp Med Biol 2021;1305:203–30.CrossRefGoogle ScholarPubMed
Wray, N.R., Lee, S.H., Mehta, D., et al. Research review: polygenic methods and their application to psychiatric traits. J Child Psychol Psychiatry 2014;55:1068–87.CrossRefGoogle ScholarPubMed
Hasin, D.S., Goodwin, R.D., Stinson, F.S., et al. Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry 2005;62:1097–1106.CrossRefGoogle ScholarPubMed
Sullivan, P.F., Daly, M.J., Ripke, S., et al. A mega-analysis of genome-wide association studies for major depressive disorder. Mol Psychiatry 2013;18:497–511.Google Scholar
Hyde, C.L., Nagle, M.W., Tian, C., et al. Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nat Genet 2016;48:1031–6.CrossRefGoogle ScholarPubMed
Wray, N.R., Ripke, S., Mattheisen, M., et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet 2018;50:668–81.CrossRefGoogle ScholarPubMed
Howard, D.M., Adams, M.J., Shirali, M., et al. Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways. Nat Commun 2018;9:1470.CrossRefGoogle ScholarPubMed
Arnau-Soler, A., Macdonald-Dunlop, E., Adams, M.J., et al. Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland. Transl Psychiatry 2019;9:14.CrossRefGoogle ScholarPubMed
Howard, D.M., Adams, M.J., Clarke, T.K., et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat Neurosci 2019;22:343–52.CrossRefGoogle ScholarPubMed
Levey, D.F., Stein, M.B., Wendt, F.R., et al. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nat Neurosci 2021;24(7):954–63.CrossRefGoogle Scholar

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