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

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 Publisher Pubmed

Amare AT^{1, 2, 3, 4} ; Vaez A^{1, 5} ; Hsu YH^{6, 7, 8} ; Direk N^{9, 10} ; Kamali Z¹¹ ; Howard DM¹² ; Mcintosh AM^{12, 13} ; Tiemeier H^{9, 14} ; Bultmann U¹⁵ ; Snieder H¹ ; Hartman CA¹⁶

Show Affiliations

1. Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
2. South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia
3. School of Medicine, University of Adelaide, Adelaide, SA, Australia
4. Division of Health Sciences, University of South Australia, Adelaide, SA, Australia
5. Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan, Iran
6. HSL Institute for Aging Research, Harvard Medical School, Boston, MA, United States
7. Program for Quantitative Genomics, Harvard School of Public Health, Boston, MA, United States
8. Broad Institute of MIT and Harvard, Cambridge, MA, United States
9. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands
10. Department of Psychiatry, School of Medicine, Dokuz Eylul University, Izmir, Turkey
11. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
12. Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, United Kingdom
13. Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom
14. Department of Psychiatry, Erasmus University Medical Center, Rotterdam, Netherlands
15. Department of Health Sciences, Community and Occupational Medicine, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
16. Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Source: Molecular Psychiatry Published:2020

Abstract

Although a genetic basis of depression has been well established in twin studies, identification of genome-wide significant loci has been difficult. We hypothesized that bivariate analyses of findings from a meta-analysis of genome-wide association studies (meta-GWASs) of the broad depression phenotype with those from meta-GWASs of self-reported and recurrent major depressive disorder (MDD), bipolar disorder and schizophrenia would enhance statistical power to identify novel genetic loci for depression. LD score regression analyses were first used to estimate the genetic correlations of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia. Then, we performed four bivariate GWAS analyses. The genetic correlations (rg ± SE) of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia were 0.79 ± 0.07, 0.24 ± 0.08, 0.53 ± 0.09 and 0.57 ± 0.05, respectively. From a total of 20 independent genome-wide significant loci, 13 loci replicated of which 8 were novel for depression. These were MUC21 for the broad depression phenotype with self-reported MDD and ZNF804A, MIR3143, PSORS1C2, STK19, SPATA31D1, RTN1 and TCF4 for the broad depression phenotype with schizophrenia. Post-GWAS functional analyses of these loci revealed their potential biological involvement in psychiatric disorders. Our results emphasize the genetic similarities among different psychiatric disorders and indicate that cross-disorder analyses may be the best way forward to accelerate gene finding for depression, or psychiatric disorders in general. © 2019, The Author(s).

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Style	Citing Format
MLA	Amare AT, et al.. "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, vol. 25, no. 7, 2020, pp. 1420-1429.
APA	Amare AT, Vaez A, Hsu YH, Direk N, Kamali Z, Howard DM, Mcintosh AM, Tiemeier H, Bultmann U, Snieder H, Hartman CA (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), 1420-1429.
Chicago	Amare AT, Vaez A, Hsu YH, Direk N, Kamali Z, Howard DM, Mcintosh AM, et al.. "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, no. 7 (2020): 1420-1429.
Harvard	Amare AT et al. (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), pp. 1420-1429.
Vancouver	Amare AT, Vaez A, Hsu YH, Direk N, Kamali Z, Howard DM, et al.. 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. 2020;25(7):1420-1429.
BibTex	@article{ author = {Amare AT and Vaez A and Hsu YH and Direk N and Kamali Z and Howard DM and Mcintosh AM and Tiemeier H and Bultmann U and Snieder H and Hartman CA}, title = {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}, journal = {Molecular Psychiatry}, volume = {25}, number = {7}, pages = {1420-1429}, year = {2020} }
RIS	TY - JOUR AU - Amare AT AU - Vaez A AU - Hsu YH AU - Direk N AU - Kamali Z AU - Howard DM AU - Mcintosh AM AU - Tiemeier H AU - Bultmann U AU - Snieder H AU - Hartman CA TI - 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 JO - Molecular Psychiatry VL - 25 IS - 7 SP - 1420 EP - 1429 PY - 2020 ER -

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