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The genetic basis of major depression

Published online by Cambridge University Press:  08 March 2021

K. M. Kendall
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
E. Van Assche
Affiliation:
Department of Psychiatry, University of Muenster, Muenster, Germany
T. F. M. Andlauer
Affiliation:
Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
K. W. Choi
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA02114, USA Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA02114, USA Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA02115, USA
J. J. Luykx
Affiliation:
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands Department of Translational Neuroscience, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands Outpatient Second Opinion Clinic, GGNet Mental Health, Warnsveld, The Netherlands
E. C. Schulte
Affiliation:
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
Y. Lu*
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
*
Author for correspondence: Y. Lu, E-mail: [email protected]

Abstract

Major depressive disorder (MDD) is a common, debilitating, phenotypically heterogeneous disorder with heritability ranges from 30% to 50%. Compared to other psychiatric disorders, its high prevalence, moderate heritability, and strong polygenicity have posed major challenges for gene-mapping in MDD. Studies of common genetic variation in MDD, driven by large international collaborations such as the Psychiatric Genomics Consortium, have confirmed the highly polygenic nature of the disorder and implicated over 100 genetic risk loci to date. Rare copy number variants associated with MDD risk were also recently identified. The goal of this review is to present a broad picture of our current understanding of the epidemiology, genetic epidemiology, molecular genetics, and gene–environment interplay in MDD. Insights into the impact of genetic factors on the aetiology of this complex disorder hold great promise for improving clinical care.

Type
Invited Review
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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References

Amare, A. T., Vaez, A., Hsu, Y. H., Direk, N., Kamali, Z., Howard, D. M., … Hartman, C. A. (2020). Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression. Molecular Psychiatry, 25(7), 110.CrossRefGoogle ScholarPubMed
Amin, N., Belonogova, N. M., Jovanova, O., Brouwer, R. W., van Rooij, J. G., van den Hout, M. C., … van Duijn, C. M. (2017a). Nonsynonymous variation in NKPD1 increases depressive symptoms in European populations. Biological Psychiatry, 81(8), 702707.CrossRefGoogle Scholar
Amin, N., De Vrij, F. M. S., Baghdadi, M., Brouwer, R. W. W., Van Rooij, J. G. J., Jovanova, O., … Van Duijn, C. M. (2018). A rare missense variant in RCL1 segregates with depression in extended families. Molecular Psychiatry, 23(5), 11201126.CrossRefGoogle ScholarPubMed
Amin, N., Jovanova, O., Adams, H. H. H., Dehghan, A., Kavousi, M., Vernooij, M. W., … Van Duijn, C. M. (2017b). Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms. Molecular Psychiatry, 22(4), 537543.CrossRefGoogle Scholar
Andlauer, T. F., & Nöthen, M. M. (2020). Polygenic scores for psychiatric disease: From research tool to clinical application. Medizinische Genetik, 32(1), 3945.CrossRefGoogle Scholar
Arloth, J., Bogdan, R., Weber, P., Frishman, G., Menke, A., Wagner, K. V., … Hariri, A. R. (2015). Genetic differences in the immediate transcriptome response to stress predict risk-related brain function and psychiatric disorders. Neuron, 86(5), 11891202.CrossRefGoogle ScholarPubMed
Arloth, J., Eraslan, G., Andlauer, T. F., Martins, J., Iurato, S., Kühnel, B., … Mueller, N. S. (2020). DeepWAS: Multivariate genotype-phenotype associations by directly integrating regulatory information using deep learning. PLoS Computational Biology, 16(2), e1007616.CrossRefGoogle ScholarPubMed
Arnau-Soler, A., Macdonald-Dunlop, E., Adams, M. J., Clarke, T. K., MacIntyre, D. J., Milburn, K., … Thomson, P. A. (2019). Genome-wide by environment interaction studies of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland. Translational Psychiatry, 9(1), 113.CrossRefGoogle ScholarPubMed
Barbu, M. C., Shen, X., Walker, R. M., Howard, D. M., Evans, K. L., Whalley, H. C., … McIntosh, A. M. (2020). Epigenetic prediction of major depressive disorder. Molecular Psychiatry. doi:10.1038/s41380-020-0808-3.Google ScholarPubMed
Baselmans, B. M., Yengo, L., van Rheenen, W., & Wray, N. R. (2020). Risk in relatives, heritability, SNP-based heritability and genetic correlations in psychiatric disorders: A review. Biological Psychiatry, 89(1), 1119.CrossRefGoogle ScholarPubMed
Beckman, G., Beckman, L., Cedergren, B., Perris, C., & Strandman, E. (1978). Serum protein and red cell enzyme polymorphisms in affective disorders. Human Heredity, 28(1), 4147.CrossRefGoogle ScholarPubMed
Bigdeli, T. B., Ripke, S., Peterson, R. E., Trzaskowski, M., Bacanu, S. A., Abdellaoui, A., … Kendler, K. S. (2017). Genetic effects influencing risk for major depressive disorder in China and Europe. Translational Psychiatry, 7(3), e1074.CrossRefGoogle ScholarPubMed
Birmaher, B., Ryan, N. D., Williamson, D. E., Brent, D. A., Kaufman, J., Dahl, R. E., … Nelson, B. (1996). Childhood and adolescent depression: A review of the past 10 years. Part I. Journal of the American Academy of Child & Adolescent Psychiatry, 35(11), 14271439.CrossRefGoogle ScholarPubMed
Border, R., Johnson, E. C., Evans, L. M., Smolen, A., Berley, N., Sullivan, P. F., & Keller, M. C. (2019a). No support for historical candidate gene or candidate gene-by-interaction hypotheses for major depression across multiple large samples. American Journal of Psychiatry, 176(5), 376387.CrossRefGoogle Scholar
Border, R., Smolen, A., Corley, R. P., Stallings, M. C., Brown, S. A., Conger, R. D., … Evans, L. M. (2019b). Imputation of behavioral candidate gene repeat variants in 486551 publicly-available UK Biobank individuals. European Journal of Human Genetics, 27(6), 963.CrossRefGoogle Scholar
Bosker, F. J., Hartman, C. A., Nolte, I. M., Prins, B. P., Terpstra, P., Posthuma, D., … Nolen, W. A. (2011). Poor replication of candidate genes for major depressive disorder using genome-wide association data. Molecular Psychiatry, 16(5), 516532.CrossRefGoogle ScholarPubMed
Bousman, C. A., Bengesser, S. A., Aitchison, K. J., Amare, A. T., Aschauer, H., Baune, B. T., … Müller, D. J. (2021). Review and consensus on pharmacogenomic testing in psychiatry. Pharmacopsychiatry, 54(1), 517.Google Scholar
Brainstorm Consortium. (2018). Analysis of shared heritability in common disorders of the brain. Science (New York, NY), 360(6395), eaap8757.CrossRefGoogle Scholar
Breen, G., Webb, B. T., Butler, A. W., Van Den Oord, E. J., Tozzi, F., Craddock, N., … McGuffin, P. (2011). A genome-wide significant linkage for severe depression on chromosome 3: The depression network study. American Journal of Psychiatry, 168(8), 840847.CrossRefGoogle ScholarPubMed
Bromet, E., Andrade, L. H., Hwang, I., Sampson, N. A., Alonso, J., De Girolamo, G., … Kessler, R. C. (2011). Cross-national epidemiology of DSM-IV major depressive episode. BMC Medicine, 9(1), 90.CrossRefGoogle ScholarPubMed
Bulik-Sullivan, B., Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P. R., … Psychiatric Genomics Consortium. (2015). An atlas of genetic correlations across human diseases and traits. Nature Genetics, 47(11), 1236.CrossRefGoogle ScholarPubMed
Byrne, E. M., Kirk, K. M., Medland, S. E., McGrath, J. J., Colodro-Conde, L., Parker, R., … Martin, N. G. (2020). Cohort profile: The Australian genetics of depression study. BMJ Open, 10(5), e032580.CrossRefGoogle ScholarPubMed
Cai, N., Choi, K. W., & Fried, E. I. (2020a). Reviewing the genetics of heterogeneity in depression: Operationalizations, manifestations and etiologies. Human Molecular Genetics, 29(R1), R10R18.CrossRefGoogle Scholar
Cai, N., Revez, J. A., Adams, M. J., Andlauer, T. F., Breen, G., Byrne, E. M., … Flint, J. (2020b). Minimal phenotyping yields genome-wide association signals of low specificity for major depression. Nature Genetics, 52(4), 437447.CrossRefGoogle Scholar
Camp, N. J., Lowry, M. R., Richards, R. L., Plenk, A. M., Carter, C., Hensel, C. H., … Cannon-Albright, L. A. (2005). Genome-wide linkage analyses of extended Utah pedigrees identifies loci that influence recurrent, early-onset major depression and anxiety disorders. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 135(1), 8593.CrossRefGoogle Scholar
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., … Poulton, R. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science (New York, N.Y.), 301(5631), 386389.CrossRefGoogle ScholarPubMed
Chan, R. F., Turecki, G., Shabalin, A. A., Guintivano, J., Zhao, M., Xie, L. Y., … van den Oord, E. J. (2020). Cell type-specific methylome-wide association studies implicate neurotrophin and innate immune signaling in major depressive disorder. Biological Psychiatry, 87(5), 431442.CrossRefGoogle ScholarPubMed
Choi, K. W., Chen, C. Y., Ursano, R. J., Sun, X., Jain, S., Kessler, R. C., … Smoller, J. W. (2020a). Prospective study of polygenic risk, protective factors, and incident depression following combat deployment in US Army soldiers. Psychological Medicine, 50(5), 737745.CrossRefGoogle Scholar
Choi, K. W., Stein, M. B., Nishimi, K. M., Ge, T., Coleman, J. R., Chen, C. Y., … Smoller, J. W. (2020b). An exposure-wide and Mendelian randomization approach to identifying modifiable factors for the prevention of depression. American Journal of Psychiatry, 177(10), 944954.CrossRefGoogle Scholar
Choi, K. W., Zheutlin, A. B., Karlson, R. A., Wang, M. J., Dunn, E. C., Stein, M. B., … Smoller, J. W. (2020c). Physical activity offsets genetic risk for incident depression assessed via electronic health records in a biobank cohort study. Depression and Anxiety, 37(2), 106114.CrossRefGoogle Scholar
Coe, B. P., Witherspoon, K., Rosenfeld, J. A., Van Bon, B. W., Vulto-van Silfhout, A. T., Bosco, P., … Eichler, E. E. (2014). Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nature Genetics, 46(10), 10631071.CrossRefGoogle ScholarPubMed
Coleman, J. R., Gaspar, H. A., Bryois, J., Byrne, E. M., Forstner, A. J., Holmans, P. A., … Lawson, W. B. (2020). The genetics of the mood disorder spectrum: Genome-wide association analyses of more than 185000 cases and 439000 controls. Biological Psychiatry, 88(2), 169184.CrossRefGoogle ScholarPubMed
CONVERGE consortium. (2015). Sparse whole-genome sequencing identifies two loci for major depressive disorder. Nature, 523(7562), 588591.CrossRefGoogle Scholar
Cooper, G. M., Coe, B. P., Girirajan, S., Rosenfeld, J. A., Vu, T. H., Baker, C., … Eichler, E. E. (2011). A copy number variation morbidity map of developmental delay. Nature Genetics, 43(9), 838846.CrossRefGoogle ScholarPubMed
Cross-Disorder Group of the PGC. (2019). Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders. Cell, 179(7), 14691482.CrossRefGoogle Scholar
Davey Smith, G., & Ebrahim, S. (2003). ‘Mendelian randomization’: Can genetic epidemiology contribute to understanding environmental determinants of disease? International Journal of Epidemiology, 32(1), 122.CrossRefGoogle Scholar
Davies, M. R., Kalsi, G., Armour, C., Jones, I. R., McIntosh, A. M., Smith, D. J., … Breen, G. (2019). The Genetic Links to Anxiety and Depression (GLAD) Study: Online recruitment into the largest recontactable study of depression and anxiety. Behaviour Research and Therapy, 123, 103503.CrossRefGoogle ScholarPubMed
Degenhardt, F., Priebe, L., Herms, S., Mattheisen, M., Mühleisen, T. W., Meier, S., … Cichon, S. (2012). Association between copy number variants in 16p11. 2 and major depressive disorder in a German case–control sample. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 159(3), 263273.CrossRefGoogle Scholar
Demirkan, A., Lahti, J., Direk, N., Viktorin, A., Lunetta, K. L., Terracciano, A., … Luik, A. I. (2016). Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: A meta-analysis of genome-wide association studies. Psychological Medicine, 46(8), 1613.CrossRefGoogle Scholar
Direk, N., Williams, S., Smith, J. A., Ripke, S., Air, T., Amare, A. T., … Sullivan, P. F. (2017). An analysis of two genome-wide association meta-analyses identifies a new locus for broad depression phenotype. Biological Psychiatry, 82(5), 322329.CrossRefGoogle ScholarPubMed
Duncan, L. E., & Keller, M. C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168(10), 10411049.CrossRefGoogle ScholarPubMed
Dunn, E. C., Sofer, T., Wang, M. J., Soare, T. W., Gallo, L. C., Gogarten, S. M., … Smoller, J. W. (2018). Genome-wide association study of depressive symptoms in the Hispanic Community Health Study/Study of Latinos. Journal of Psychiatric Research, 99, 167176.CrossRefGoogle ScholarPubMed
Dunn, E. C., Wiste, A., Radmanesh, F., Almli, L. M., Gogarten, S. M., Sofer, T., … Smoller, J. W. (2016). Genome-wide association study (GWAS) and genome-wide by environment interaction study (GWEIS) of depressive symptoms in African American and Hispanic/Latina women. Depression and Anxiety, 33(4), 265280.CrossRefGoogle ScholarPubMed
Fabbri, C., Kasper, S., Kautzky, A., Zohar, J., Souery, D., Montgomery, S., … Serretti, A. (2020). A polygenic predictor of treatment-resistant depression using whole exome sequencing and genome-wide genotyping. Translational Psychiatry, 10(1), 112.CrossRefGoogle ScholarPubMed
Farrell, M. S., Werge, T., Sklar, P., Owen, M. J., Ophoff, R. A., O'Donovan, M. C., … Sullivan, P. F. (2015). Evaluating historical candidate genes for schizophrenia. Molecular Psychiatry, 20(5), 555562.CrossRefGoogle Scholar
Fernandez-Pujals, A. M., Adams, M. J., Thomson, P., McKechanie, A. G., Blackwood, D. H., Smith, B. H., … McIntosh, A. M. (2015). Epidemiology and heritability of major depressive disorder, stratified by age of onset, sex, and illness course in Generation Scotland: Scottish Family Health Study (GS: SFHS). PLoS ONE, 10(11), e0142197.CrossRefGoogle Scholar
Flint, J., & Kendler, K. S. (2014). The genetics of major depression. Neuron, 81(3), 484503.CrossRefGoogle ScholarPubMed
Foo, J. C., Streit, F., Frank, J., Witt, S. H., Treutlein, J., Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, … 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), 3545.CrossRefGoogle ScholarPubMed
Fried, E. I., Coomans, F., & Lorenzo-Luaces, L. (2020). The 341 737 ways of qualifying for the melancholic specifier. The Lancet Psychiatry, 7(6), 479480.CrossRefGoogle ScholarPubMed
GBD 2017 DALYs and HALE Collaborators. (2018). Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet, 392(10159), 18591922.CrossRefGoogle Scholar
Glessner, J. T., Wang, K., Sleiman, P. M., Zhang, H., Kim, C. E., Flory, J. H., … Hakonarson, H. (2010). Duplication of the SLIT3 locus on 5q35. 1 predisposes to major depressive disorder. PLoS ONE, 5(12), e15463.CrossRefGoogle ScholarPubMed
Grotzinger, A. D., Rhemtulla, M., de Vlaming, R., Ritchie, S. J., Mallard, T. T., Hill, W. D., … Tucker-Drob, E. M. (2019). Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits. Nature Human Behaviour, 3(5), 513525.CrossRefGoogle ScholarPubMed
Hall, L. S., Adams, M. J., Arnau-Soler, A., Clarke, T. K., Howard, D. M., Zeng, Y., … McIntosh, A. M. (2018). Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank. Translational Psychiatry, 8(1), 112.CrossRefGoogle ScholarPubMed
Halldorsdottir, T., Piechaczek, C., Soares de Matos, A. P., Czamara, D., Pehl, V., Wagenbuechler, P., … Binder, E. B. (2019). Polygenic risk: Predicting depression outcomes in clinical and epidemiological cohorts of youths. American Journal of Psychiatry, 176(8), 615625.CrossRefGoogle ScholarPubMed
Hek, K., Demirkan, A., Lahti, J., Terracciano, A., Teumer, A., Cornelis, M. C., … Murabito, J. (2013). A genome-wide association study of depressive symptoms. Biological Psychiatry, 73(7), 667678.CrossRefGoogle ScholarPubMed
Hek, K., Mulder, C. L., Luijendijk, H. J., van Duijn, C. M., Hofman, A., Uitterlinden, A. G., & Tiemeier, H. (2010). The PCLO gene and depressive disorders: Replication in a population-based study. Human Molecular Genetics, 19(4), 731734.CrossRefGoogle ScholarPubMed
Hemani, G., Yang, J., Vinkhuyzen, A., Powell, J. E., Willemsen, G., Hottenga, J. J., … Visscher, P. M. (2013). Inference of the genetic architecture underlying BMI and height with the use of 20,240 sibling pairs. The American Journal of Human Genetics, 93(5), 865875.CrossRefGoogle ScholarPubMed
Holmans, P., Weissman, M. M., Zubenko, G. S., Scheftner, W. A., Crowe, R. R., DePaulo, M. D. J. R. Jr., … Levinson, D. F. (2007). Genetics of recurrent early-onset major depression (GenRED): Final genome scan report. American Journal of Psychiatry, 164(2), 248258.CrossRefGoogle ScholarPubMed
Holmans, P., Zubenko, G. S., Crowe, R. R., DePaulo, J. R. Jr., Scheftner, W. A., Weissman, M. M., … Levinson, D. F. (2004). Genomewide significant linkage to recurrent, early-onset major depressive disorder on chromosome 15q. The American Journal of Human Genetics, 74(6), 11541167.CrossRefGoogle ScholarPubMed
Howard, D. M., Adams, M. J., Clarke, T. K., Hafferty, J. D., Gibson, J., Shirali, M., … 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), 343352.CrossRefGoogle ScholarPubMed
Howard, D. M., Adams, M. J., Shirali, M., Clarke, T. K., Marioni, R. E., Davies, G., … McIntosh, A. M. (2018). Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways. Nature Communications, 9(1), 110.Google ScholarPubMed
Hyde, C. L., Nagle, M. W., Tian, C., Chen, X., Paciga, S. A., Wendland, J. R., … Winslow, A. R. (2016). Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature Genetics, 48(9), 10311036.CrossRefGoogle ScholarPubMed
International Schizophrenia Consortium (2008). Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature, 455(7210), 237.CrossRefGoogle Scholar
Kang, H. J., Park, Y., Yoo, K. H., Kim, K. T., Kim, E. S., Kim, J. W., … Kim, J. M. (2020). Sex differences in the genetic architecture of depression. Scientific Reports, 10(1), 112.Google ScholarPubMed
Kendall, K. M., Rees, E., Bracher-Smith, M., Legge, S., Riglin, L., Zammit, S., … Walters, J. T. R. (2019). Association of rare copy number variants with risk of depression. JAMA Psychiatry, 76(8), 818825.CrossRefGoogle ScholarPubMed
Kendler, K. S., Gatz, M., Gardner, C. O., & Pedersen, N. L. (2006). A Swedish national twin study of lifetime major depression. American Journal of Psychiatry, 163(1), 109114.CrossRefGoogle ScholarPubMed
Kendler, K. S., Ohlsson, H., Lichtenstein, P., Sundquist, J., & Sundquist, K. (2018a). The genetic epidemiology of treated major depression in Sweden. American Journal of Psychiatry, 175(11), 11371144.CrossRefGoogle Scholar
Kendler, K. S., Ohlsson, H., Sundquist, K., & Sundquist, J. (2018b). Sources of parent-offspring resemblance for major depression in a national Swedish extended adoption study. JAMA Psychiatry, 75(2), 194200.CrossRefGoogle Scholar
Kessler, R. C., & Bromet, E. J. (2013). The epidemiology of depression across cultures. Annual Review of Public Health, 34, 119138.CrossRefGoogle ScholarPubMed
Khera, A. V., Chaffin, M., Aragam, K. G., Haas, M. E., Roselli, C., Choi, S. H., … Kathiresan, S. (2018). Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nature Genetics, 50(9), 12191224.CrossRefGoogle ScholarPubMed
Kohli, M. A., Lucae, S., Saemann, P. G., Schmidt, M. V., Demirkan, A., Hek, K., … Binder, E. B. (2011). The neuronal transporter gene SLC6A15 confers risk to major depression. Neuron, 70(2), 252265.CrossRefGoogle ScholarPubMed
Lee, S., Abecasis, G. R., Boehnke, M., & Lin, X. (2014). Rare-variant association analysis: Study designs and statistical tests. The American Journal of Human Genetics, 95(1), 523.CrossRefGoogle ScholarPubMed
Lee, S. H., Yang, J., Goddard, M. E., Visscher, P. M., & Wray, N. R. (2012). Estimation of pleiotropy between complex diseases using single-nucleotide polymorphism-derived genomic relationships and restricted maximum likelihood. Bioinformatics (Oxford, England), 28(19), 25402542.CrossRefGoogle ScholarPubMed
Levey, D. F., Stein, M. B., Wendt, F. R., Pathak, G. A., Zhou, H., Aslan, M., … Gelernter, J. (2020). GWAS of depression phenotypes in the million veteran program and meta-analysis in more than 1.2 million participants yields 178 independent risk loci. medRxiv. doi:10.1101/2020.05.18.20100685.Google Scholar
Levinson, D. F., Evgrafov, O. V., Knowles, J. A., Potash, J. B., Weissman, M. M., Scheftner, W. A., … Holmans, P. (2007). Genetics of recurrent early-onset major depression (GenRED): Significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers. American Journal of Psychiatry, 164(2), 259264.CrossRefGoogle ScholarPubMed
Levinson, D. F., Mostafavi, S., Milaneschi, Y., Rivera, M., Ripke, S., Wray, N. R., & Sullivan, P. F. (2014). Genetic studies of major depressive disorder: Why are there no genome-wide association study findings and what can we do about it? Biological Psychiatry, 76(7), 510512.CrossRefGoogle Scholar
Lewis, C. M., Ng, M. Y., Butler, A. W., Cohen-Woods, S., Uher, R., Pirlo, K., … McGuffin, P. (2010). Genome-wide association study of major recurrent depression in the UK population. American Journal of Psychiatry, 167(8), 949957.CrossRefGoogle Scholar
Lewis, C. M., & Vassos, E. (2020). Polygenic risk scores: From research tools to clinical instruments. Genome Medicine, 12, 111.CrossRefGoogle ScholarPubMed
Li, S., Li, Y., Li, X., Liu, J., Huo, Y., Wang, J., … Luo, X. J. (2020). Regulatory mechanisms of major depressive disorder risk variants. Molecular Psychiatry, 25, 19261945.CrossRefGoogle ScholarPubMed
Li, X., Luo, Z., Gu, C., Hall, L. S., McIntosh, A. M., Zeng, Y., … Luo, X. J. (2018). Common variants on 6q16. 2, 12q24. 31 and 16p13. 3 are associated with major depressive disorder. Neuropsychopharmacology, 43(10), 21462153.CrossRefGoogle ScholarPubMed
Lin, P. Y., Huang, Y. C., & Hung, C. F. (2016). Shortened telomere length in patients with depression: A meta-analytic study. Journal of Psychiatric Research, 76, 8493.CrossRefGoogle ScholarPubMed
Liu, W., & Rodgers, G. P. (2016). Olfactomedin 4 expression and functions in innate immunity, inflammation, and cancer. Cancer and Metastasis Reviews, 35(2), 201212.CrossRefGoogle ScholarPubMed
Lynch, M., & Walsh, B. (1998). Genetics and analysis of quantitative traits (Vol. 1, pp. 535557). Sunderland, MA: Sinauer.Google Scholar
Malhi, G. S., & Mann, J. J. (2018). Depression. The Lancet, 392, 22992312.CrossRefGoogle ScholarPubMed
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., … Visscher, P. M. (2009). Finding the missing heritability of complex diseases. Nature, 461(7265), 747753.CrossRefGoogle ScholarPubMed
Martin, A. R., Gignoux, C. R., Walters, R. K., Wojcik, G. L., Neale, B. M., Gravel, S., … Kenny, E. E. (2017). Human demographic history impacts genetic risk prediction across diverse populations. The American Journal of Human Genetics, 100(4), 635649.CrossRefGoogle ScholarPubMed
McIntosh, A. M., Sullivan, P. F., & Lewis, C. M. (2019). Uncovering the genetic architecture of major depression. Neuron, 102(1), 91103.CrossRefGoogle ScholarPubMed
Middeldorp, C. M., Hottenga, J. J., Slagboom, P. E., Sullivan, P. F., de Geus, E. J., Posthuma, D., … Boomsma, D. I. (2008). Linkage on chromosome 14 in a genome-wide linkage study of a broad anxiety phenotype. Molecular Psychiatry, 13(1), 8489.CrossRefGoogle Scholar
Milaneschi, Y., Lamers, F., Peyrot, W. J., Baune, B. T., Breen, G., Dehghan, A., … Penninx, B. W. (2017). Genetic association of major depression with atypical features and obesity-related immunometabolic dysregulations. JAMA Psychiatry, 74(12), 12141225.CrossRefGoogle ScholarPubMed
Moskvina, V., Farmer, A., Swainson, V., O'Leary, J., Gunasinghe, C., Owen, M., … Korszun, A. (2007). Interrelationship of childhood trauma, neuroticism, and depressive phenotype. Depression and Anxiety, 24(3), 163168.CrossRefGoogle ScholarPubMed
Muglia, P., Tozzi, F., Galwey, N. W., Francks, C., Upmanyu, R., Kong, X. Q., … Roses, A. D. (2010). Genome-wide association study of recurrent major depressive disorder in two European case–control cohorts. Molecular Psychiatry, 15(6), 589601.CrossRefGoogle ScholarPubMed
Mullins, N., Power, R. A., Fisher, H. L., Hanscombe, K. B., Euesden, J., Iniesta, R., … Lewis, C. M. (2016). Polygenic interactions with environmental adversity in the aetiology of major depressive disorder. Psychological Medicine, 46(4), 759770.CrossRefGoogle ScholarPubMed
Musliner, K. L., Mortensen, P. B., McGrath, J. J., Suppli, N. P., Hougaard, D. M., Bybjerg-Grauholm, J., … Agerbo, E. (2019). Association of polygenic liabilities for major depression, bipolar disorder, and schizophrenia with risk for depression in the Danish population. JAMA Psychiatry, 76(5), 516525.CrossRefGoogle ScholarPubMed
Ni, G., van der Werf, J., Zhou, X., Hyppönen, E., Wray, N. R., & Lee, S. H. (2019). Genotype–covariate correlation and interaction disentangled by a whole-genome multivariate reaction norm model. Nature Communications, 10(1), 115.CrossRefGoogle ScholarPubMed
Ning, Z., Pawitan, Y., & Shen, X. (2020). High-definition likelihood inference of genetic correlations across human complex traits. Nature Genetics, 52(8), 859864.CrossRefGoogle ScholarPubMed
Nishino, J., Ochi, H., Kochi, Y., Tsunoda, T., & Matsui, S. (2018). Sample size for successful genome-wide association study of major depressive disorder. Frontiers in Genetics, 9, 227.CrossRefGoogle ScholarPubMed
Noh, K., Lee, H., Choi, T. Y., Joo, Y., Kim, S. J., Kim, H., … Lee, S. J. (2019). Negr1 controls adult hippocampal neurogenesis and affective behaviors. Molecular Psychiatry, 24(8), 11891205.CrossRefGoogle ScholarPubMed
O'Dushlaine, C., Ripke, S., Ruderfer, D. M., Hamilton, S. P., Fava, M., Iosifescu, D. V., … Perlis, R. H. (2014). Rare copy number variation in treatment-resistant major depressive disorder. Biological Psychiatry, 76(7), 536541.CrossRefGoogle ScholarPubMed
Okbay, A., Baselmans, B. M., De Neve, J. E., Turley, P., Nivard, M. G., Fontana, M. A., … Rich, S. S. (2016). Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nature Genetics, 48(6), 624633.CrossRefGoogle ScholarPubMed
Ormel, J., Hartman, C. A., & Snieder, H. (2019). The genetics of depression: Successful genome-wide association studies introduce new challenges. Translational Psychiatry, 9(1), 110.CrossRefGoogle ScholarPubMed
Perlis, R. H., Ruderfer, D., Hamilton, S. P., & Ernst, C.. (2012). Copy number variation in subjects with major depressive disorder who attempted suicide. PLOS One, 7(9), e46315.CrossRefGoogle ScholarPubMed
Peterson, R. E., Cai, N., Bigdeli, T. B., Li, Y., Reimers, M., Nikulova, N., … Kendler, K. S. (2017). The genetic architecture of major depressive disorder in Han Chinese women. JAMA Psychiatry, 74(2), 162168.CrossRefGoogle ScholarPubMed
Peterson, R. E., Cai, N., Dahl, A. W., Bigdeli, T. B., Edwards, A. C., Webb, B. T., … Kendler, K. S. (2018). Molecular genetic analysis subdivided by adversity exposure suggests etiologic heterogeneity in major depression. American Journal of Psychiatry, 175(6), 545554.CrossRefGoogle ScholarPubMed
Peyrot, W. J., Milaneschi, Y., Abdellaoui, A., Sullivan, P. F., Hottenga, J. J., Boomsma, D. I., & Penninx, B. W. (2014). Effect of polygenic risk scores on depression in childhood trauma. The British Journal of Psychiatry, 205(2), 113119.CrossRefGoogle ScholarPubMed
Peyrot, W. J., Van der Auwera, S., Milaneschi, Y., Dolan, C. V., Madden, P. A., Sullivan, P. F., … Yang, J. (2018). Does childhood trauma moderate polygenic risk for depression? A meta-analysis of 5765 subjects from the psychiatric genomics consortium. Biological Psychiatry, 84(2), 138147.CrossRefGoogle ScholarPubMed
Pirooznia, M., Wang, T., Avramopoulos, D., Potash, J. B., Zandi, P. P., & Goes, F. S. (2016). High-throughput sequencing of the synaptome in major depressive disorder. Molecular Psychiatry, 21(5), 650655.CrossRefGoogle ScholarPubMed
Polderman, T. J., Benyamin, B., De Leeuw, C. A., Sullivan, P. F., Van Bochoven, A., Visscher, P. M., & Posthuma, D. (2015). Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nature Genetics, 47(7), 702709.CrossRefGoogle ScholarPubMed
Polubriaginof, F. C., Vanguri, R., Quinnies, K., Belbin, G. M., Yahi, A., Salmasian, H., … Tatonetti, N. P. (2018). Disease heritability inferred from familial relationships reported in medical records. Cell, 173(7), 16921704.CrossRefGoogle ScholarPubMed
Power, R. A., Tansey, K. E., Buttenschøn, H. N., Cohen-Woods, S., Bigdeli, T., Hall, L. S., … GERAD1 Consortium. (2017). Genome-wide association for major depression through age at onset stratification: Major depressive disorder working group of the psychiatric genomics consortium. Biological Psychiatry, 81(4), 325335.CrossRefGoogle Scholar
Provencal, N., & Binder, E. B. (2015). The neurobiological effects of stress as contributors to psychiatric disorders: Focus on epigenetics. Current Opinion in Neurobiology, 30, 3137.CrossRefGoogle ScholarPubMed
Purcell, S., & Sham, P. (2002). Variance components models for gene–environment interaction in quantitative trait locus linkage analysis. Twin Research and Human Genetics, 5(6), 572576.CrossRefGoogle ScholarPubMed
Rice, S. M., Fallon, B. J., Aucote, H. M., Möller-Leimkühler, A., Treeby, M. S., & Amminger, G. P. (2015). Longitudinal sex differences of externalising and internalising depression symptom trajectories: Implications for assessment of depression in men from an online study. International Journal of Social Psychiatry, 61(3), 236240.CrossRefGoogle ScholarPubMed
Rietschel, M., Mattheisen, M., Frank, J., Treutlein, J., Degenhardt, F., Breuer, R., … Cichon, S. (2010). Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression. Biological Psychiatry, 68(6), 578585.CrossRefGoogle ScholarPubMed
Schizophrenia Working Group of the PGC, Ripke, S., Walters, J. T., & O'Donovan, M. C. (2020). Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia. MedRxiv, 10.1101/2020.09.12.20192922.Google Scholar
Ripke, S., Wray, N. R., Lewis, C. M., Hamilton, S. P., Weissman, M. M., Breen, G., … Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium. (2013). A mega-analysis of genome-wide association studies for major depressive disorder. Molecular Psychiatry, 18(4), 497.Google ScholarPubMed
Rucker, J. J., Breen, G., Pinto, D., Pedroso, I., Lewis, C. M., Cohen-Woods, S., … McGuffin, P. (2013). Genome-wide association analysis of copy number variation in recurrent depressive disorder. Molecular Psychiatry, 18(2), 183189.CrossRefGoogle ScholarPubMed
Rucker, J. J., Tansey, K. E., Rivera, M., Pinto, D., Cohen-Woods, S., Uher, R., … Breen, G. (2016). Phenotypic association analyses with copy number variation in recurrent depressive disorder. Biological Psychiatry, 79(4), 329336.CrossRefGoogle ScholarPubMed
Schijven, D., Veldink, J. H., & Luykx, J. J. (2020). Genetic cross-disorder analysis in psychiatry: From methodology to clinical utility. The British Journal of Psychiatry, 216(5), 246249.CrossRefGoogle ScholarPubMed
Schiweck, C., Claes, S., Van Oudenhove, L., Lafit, G., Vaessen, T., de Beeck, G. O., … Vrieze, E. (2020). Childhood trauma, suicide risk and inflammatory phenotypes of depression: Insights from monocyte gene expression. Translational Psychiatry, 10(1), 112.CrossRefGoogle ScholarPubMed
Schol-Gelok, S., Janssens, A. C. J., Tiemeier, H., Liu, F., Lopez-Leon, S., Zorkoltseva, I. V., … van Duijn, C. M. (2010). A genome-wide screen for depression in two independent Dutch populations. Biological Psychiatry, 68(2), 187196.CrossRefGoogle ScholarPubMed
Schwabe, I., Milaneschi, Y., Gerring, Z., Sullivan, P. F., Schulte, E., Suppli, N. P., … Middeldorp, C. M. (2019). Unraveling the genetic architecture of major depressive disorder: Merits and pitfalls of the approaches used in genome-wide association studies. Psychological Medicine, 49(16), 26462656.CrossRefGoogle ScholarPubMed
Shadrina, M., Bondarenko, E. A., & Slominsky, P. A. (2018). Genetics factors in major depression disease. Frontiers in Psychiatry, 9, 334.CrossRefGoogle ScholarPubMed
Shen, X., Howard, D. M., Adams, M. J., Hill, W. D., Clarke, T. K., Deary, I. J., … McIntosh, A. M. (2020). A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank. Nature Communications, 11(1), 116.CrossRefGoogle ScholarPubMed
Shi, J., Potash, J. B., Knowles, J. A., Weissman, M. M., Coryell, W., Scheftner, W. A., … Levinson, D. F. (2011). Genome-wide association study of recurrent early-onset major depressive disorder. Molecular Psychiatry, 16(2), 193201.CrossRefGoogle ScholarPubMed
Shyn, S. I., Shi, J., Kraft, J. B., Potash, J. B., Knowles, J. A., Weissman, M. M., … Hamilton, S. P. (2011). Novel loci for major depression identified by genome-wide association study of sequenced treatment alternatives to relieve depression and meta-analysis of three studies. Molecular Psychiatry, 16(2), 202215.CrossRefGoogle ScholarPubMed
Smith, D. J., Nicholl, B. I., Cullen, B., Martin, D., Ul-Haq, Z., Evans, J., … Pell, J. P. (2013). Prevalence and characteristics of probable major depression and bipolar disorder within UK biobank: Cross-sectional study of 172,751 participants. PLoS ONE, 8(11), e75362.CrossRefGoogle ScholarPubMed
Stahl, E. A., Breen, G., Forstner, A. J., McQuillin, A., Ripke, S., Trubetskoy, V., … Reif, A. (2019). Genome-wide association study identifies 30 loci associated with bipolar disorder. Nature Genetics, 51(5), 793803.CrossRefGoogle ScholarPubMed
Stefansson, H., Rujescu, D., Cichon, S., Pietiläinen, O. P., Ingason, A., Steinberg, S., … Stefansson, K. (2008). Large recurrent microdeletions associated with schizophrenia. Nature, 455(7210), 232236.CrossRefGoogle ScholarPubMed
Stringa, N., Milaneschi, Y., van Schoor, N. M., Suanet, B., van der Lee, S., Holstege, H., … Huisman, M. (2020). Genetic liability for depression, social factors and their interaction effect in depressive symptoms and depression over time in older adults. The American Journal of Geriatric Psychiatry, 28(8), 844855.CrossRefGoogle ScholarPubMed
Subaran, R. L., Odgerel, Z., Swaminathan, R., Glatt, C. E., & Weissman, M. M. (2016). Novel variants in ZNF34 and other brain-expressed transcription factors are shared among early-onset MDD relatives. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 171(3), 333341.CrossRefGoogle Scholar
Sullivan, P. F., de Geus, E. J., Willemsen, G., James, M. R., Smit, J. H., Zandbelt, T., … Penninx, B. W. (2009). Genome-wide association for major depressive disorder: A possible role for the presynaptic protein piccolo. Molecular Psychiatry, 14(4), 359375.CrossRefGoogle ScholarPubMed
Sullivan, P. F., Neale, M. C., & Kendler, K. S. (2000). Genetic epidemiology of major depression: Review and meta-analysis. American Journal of Psychiatry, 157(10), 15521562.CrossRefGoogle ScholarPubMed
Tansey, K. E., Rucker, J. J., Kavanagh, D. H., Guipponi, M., Perroud, N., Bondolfi, G., … Uher, R. (2014). Copy number variants and therapeutic response to antidepressant medication in major depressive disorder. The Pharmacogenomics Journal, 14(4), 395399.CrossRefGoogle ScholarPubMed
Tombácz, D., Maróti, Z., Kalmár, T., Csabai, Z., Balázs, Z., Takahashi, S., … Boldogkői, Z. (2017). High-coverage whole-exome sequencing identifies candidate genes for suicide in victims with major depressive disorder. Scientific Reports, 7(1), 111.CrossRefGoogle ScholarPubMed
Turley, P., Walters, R. K., Maghzian, O., Okbay, A., Lee, J. J., Fontana, M. A., … Benjamin, D. J. (2018). Multi-trait analysis of genome-wide association summary statistics using MTAG. Nature Genetics, 50(2), 229237.CrossRefGoogle ScholarPubMed
Van Assche, E., Moons, T., Cinar, O., Viechtbauer, W., Oldehinkel, A. J., Van Leeuwen, K., … van Winkel, R. (2017a). Gene-based interaction analysis shows GABA ergic genes interacting with parenting in adolescent depressive symptoms. Journal of Child Psychology and Psychiatry, 58(12), 13011309.CrossRefGoogle Scholar
Van Assche, E., Vangeel, E., Freson, K., Van Leeuwen, K., Verschueren, K., Colpin, H., … Claes, S. (2017b). Epigenome-wide analysis of methylation and perceived parenting in adolescents and its correlation with depressive symptoms over time. European Neuropsychopharmacology, 27, S449S450.CrossRefGoogle Scholar
Van der Auwera, S., Peyrot, W. J., Milaneschi, Y., Hertel, J., Baune, B., Breen, G., … Grabe, H. (2018). Genome-wide gene-environment interaction in depression: A systematic evaluation of candidate genes: The childhood trauma working-group of PGC-MDD. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 177(1), 4049.CrossRefGoogle ScholarPubMed
Van Rheenen, W., Peyrot, W. J., Schork, A. J., Lee, S. H., & Wray, N. R. (2019). Genetic correlations of polygenic disease traits: From theory to practice. Nature Reviews Genetics, 20(10), 567581.CrossRefGoogle ScholarPubMed
Viktorin, A., Meltzer-Brody, S., Kuja-Halkola, R., Sullivan, P. F., Landén, M., Lichtenstein, P., & Magnusson, P. K. (2016). Heritability of perinatal depression and genetic overlap with nonperinatal depression. American Journal of Psychiatry, 173(2), 158165.CrossRefGoogle ScholarPubMed
Visscher, P. M., Hill, W. G., & Wray, N. R. (2008). Heritability in the genomics era – concepts and misconceptions. Nature Reviews Genetics, 9(4), 255266.CrossRefGoogle ScholarPubMed
Wang, X., Cheng, W., Zhu, J., Yin, H., Chang, S., Yue, W., & Yu, H. (2020). Integrating genome-wide association study and expression quantitative trait loci data identifies NEGR1 as a causal risk gene of major depression disorder. Journal of Affective Disorders, 265, 679686.CrossRefGoogle ScholarPubMed
Ware, E. B., Mukherjee, B., Sun, Y. V., Diez-Roux, A. V., Kardia, S. L., & Smith, J. A. (2015). Comparative genome-wide association studies of a depressive symptom phenotype in a repeated measures setting by race/ethnicity in the multi-ethnic study of atherosclerosis. BMC Genetics, 16(1), 118.CrossRefGoogle Scholar
Wong, M. L., Arcos-Burgos, M., Liu, S., Velez, J. I., Yu, C., Baune, B. T., … Licinio, J. (2017). The PHF21B gene is associated with major depression and modulates the stress response. Molecular Psychiatry, 22(7), 10151025.CrossRefGoogle ScholarPubMed
Wray, N. R., & Gottesman, I. I. (2012). Using summary data from the Danish national registers to estimate heritabilities for schizophrenia, bipolar disorder, and major depressive disorder. Frontiers in Genetics, 3, 118.CrossRefGoogle ScholarPubMed
Wray, N. R., Lee, S. H., Mehta, D., Vinkhuyzen, A. A., Dudbridge, F., & Middeldorp, C. M. (2014). Research review: Polygenic methods and their application to psychiatric traits. Journal of Child Psychology and Psychiatry, 55(10), 10681087.CrossRefGoogle ScholarPubMed
Wray, N. R., Pergadia, M. L., Blackwood, D. H. R., Penninx, B. W. J. H., Gordon, S. D., Nyholt, D. R., … Sullivan, P. F. (2012). Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned. Molecular Psychiatry, 17(1), 3648.CrossRefGoogle ScholarPubMed
Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., … Viktorin, A. (2018). Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nature Genetics, 50(5), 668681.CrossRefGoogle ScholarPubMed
Yu, C., Arcos-Burgos, M., Baune, B. T., Arolt, V., Dannlowski, U., Wong, M. L., & Licinio, J. (2018). Low-frequency and rare variants may contribute to elucidate the genetics of major depressive disorder. Translational Psychiatry, 8(1), 18.CrossRefGoogle ScholarPubMed
Yu, C., Baune, B. T., Wong, M. L., & Licinio, J. (2017). Investigation of copy number variation in subjects with major depression based on whole-genome sequencing data. Journal of Affective Disorders, 220, 3842.CrossRefGoogle ScholarPubMed
Zhang, X., Abdellaoui, A., Rucker, J., de Jong, S., Potash, J. B., Weissman, M. M., … Levinson, D. F. (2019). Genome-wide burden of rare short deletions is enriched in major depressive disorder in four cohorts. Biological Psychiatry, 85(12), 10651073.CrossRefGoogle ScholarPubMed
Zhang, Y., Li, M., Wang, Q., Hsu, J. S., Deng, W., Ma, X., … Li, T. (2020). A joint study of whole exome sequencing and structural MRI analysis in major depressive disorder. Psychological Medicine, 50(3), 384395.CrossRefGoogle ScholarPubMed
Zhong, J., Li, S., Zeng, W., Li, X., Gu, C., Liu, J., & Luo, X. J. (2019). Integration of GWAS and brain eQTL identifies FLOT1 as a risk gene for major depressive disorder. Neuropsychopharmacology, 44(9), 15421551.CrossRefGoogle ScholarPubMed
Zilhão, N. R., Abdellaoui, A., Smit, D. J. A., Cath, D. C., Hottenga, J. J., & Boomsma, D. I. (2018). Polygenic prediction of obsessive compulsive symptoms. Molecular Psychiatry, 23, 168169.CrossRefGoogle ScholarPubMed
Zubenko, G. S., Maher, B., Hughes, H. B. III., Zubenko, W. N., Stiffler, J. S., Kaplan, B. B., & Marazita, M. L. (2003). Genome-wide linkage survey for genetic loci that influence the development of depressive disorders in families with recurrent, early-onset, major depression. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 123(1), 118.Google Scholar