Log in

Genetic network structure of 13 psychiatric disorders in the general population

  • Short Communication
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Psychiatric disorders frequently co-occur and share common symptoms and genetic backgrounds. Previous research has used genome-wide association studies to identify the interrelationships among psychiatric disorders and identify clusters of disorders; however, these methods have limitations in terms of their ability to examine the relationships among disorders as a network structure and their generalizability to the general population. In this study, we explored the network structure of the polygenic risk score (PRS) for 13 psychiatric disorders in a general population (276,249 participants of European ancestry from the UK Biobank) and identified communities and the centrality of the network. In this network, the nodes represented a PRS for each psychiatric disorder and the edges represented the connections between nodes. The psychiatric disorders comprised four robust communities. The first community included attention-deficit hyperactivity disorder, autism spectrum disorder, major depressive disorder, and anxiety disorder. The second community consisted of bipolar I and II disorders, schizophrenia, and anorexia nervosa. The third group included Tourette’s syndrome and obsessive–compulsive disorder. Cannabis use disorder, alcohol use disorder, and post-traumatic stress disorder make up the fourth community. The PRS of schizophrenia had the highest values for the three metrics (strength, betweenness, and closeness) in the network. Our findings provide a comprehensive genetic network of psychiatric disorders and biological evidence for the classification of psychiatric disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Data availability

The data are available from the corresponding author upon reasonable request.

References

  1. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE (2005) Prevalence, severity, and comorbidity of 12-month dsm-iv disorders in the national comorbidity survey replication. Arch Gen Psychiatry 62:617–627

    Article  PubMed  PubMed Central  Google Scholar 

  2. Caspi A, Moffitt TE (2018) All for one and one for all: mental disorders in one dimension. Am J Psychiatry 175:831–844

    Article  PubMed  PubMed Central  Google Scholar 

  3. Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, Duncan L, Escott-Price V, Falcone GJ, Gormley P, Malik R (2018) Analysis of shared heritability in common disorders of the brain. Science 360:eaap8757

    Article  PubMed  Google Scholar 

  4. Romero C, Werme J, Jansen PR, Gelernter J, Stein MB, Levey D, Polimanti R, de Leeuw C, Posthuma D, Nagel M, van der Sluis S (2022) Exploring the genetic overlap between twelve psychiatric disorders. Nat Genet 54:1795–1802

    Article  CAS  PubMed  Google Scholar 

  5. Lee PH, Anttila V, Won H, Feng Y-CA, Rosenthal J, Zhu Z, Tucker-Drob EM, Nivard MG, Grotzinger AD, Posthuma D (2019) Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders. Cell 179(1469–1482):e1411

    Google Scholar 

  6. Grotzinger AD, Mallard TT, Akingbuwa WA, Ip HF, Adams MJ, Lewis CM, McIntosh AM, Grove J, Dalsgaard S, Lesch KP, Strom N, Meier SM, Mattheisen M, Børglum AD, Mors O, Breen G, Lee PH, Kendler KS, Smoller JW, Tucker-Drob EM, Nivard MG (2022) Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis. Nat Genet 54:548–559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kendler KS (2006) Reflections on the relationship between psychiatric genetics and psychiatric nosology. Am J Psychiatry 163:1138–1146

    Article  PubMed  Google Scholar 

  8. Borsboom D, Cramer AO (2013) Network analysis: An integrative approach to the structure of psychopathology. Annu Rev Clin Psychol 9:91–121

    Article  PubMed  Google Scholar 

  9. Borsboom D (2017) A network theory of mental disorders. World Psychiatry 16:5–13

    Article  PubMed  PubMed Central  Google Scholar 

  10. International Schizophrenia C, Purcell SM, Wray NR, Stone JL, Visscher PM, O’Donovan MC, Sullivan PF, Sklar P (2009) Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460:748–752

    Article  Google Scholar 

  11. Wray NR, Goddard ME, Visscher PM (2007) Prediction of individual genetic risk to disease from genome-wide association studies. Genome Res 17:1520–1528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. O’Connell J, Sharp K, Shrine N, Wain L, Hall I, Tobin M, Zagury JF, Delaneau O, Marchini J (2016) Haplotype estimation for biobank-scale data sets. Nat Genet 48:817–820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Howie BN, Donnelly P, Marchini J (2009) A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 5:e1000529

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ge T, Chen C-Y, Ni Y, Feng Y-CA, Smoller JW (2019) Polygenic prediction via bayesian regression and continuous shrinkage priors. Nat Commun 10:1776

    Article  PubMed  PubMed Central  Google Scholar 

  15. Epskamp S, Fried EI (2018) A tutorial on regularized partial correlation networks. Psychol Methods 23:617

    Article  PubMed  Google Scholar 

  16. Fried EI, Eidhof MB, Palic S, Costantini G, Huisman-van Dijk HM, Bockting CL, Engelhard I, Armour C, Nielsen AB, Karstoft K-I (2018) Replicability and generalizability of posttraumatic stress disorder (ptsd) networks: a cross-cultural multisite study of ptsd symptoms in four trauma patient samples. Clin Psychol Sci 6:335–351

    Article  PubMed  PubMed Central  Google Scholar 

  17. Golino HF, Epskamp S (2017) Exploratory graph analysis: a new approach for estimating the number of dimensions in psychological research. PLoS ONE 12:e0174035

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ghosh S, Halappanavar M, Tumeo A, Kalyanaraman A, Lu H, Chavarria-Miranda D, Khan A, Gebremedhin A (2018) Distributed Louvain algorithm for graph community detection. In: 2018 IEEE international parallel and distributed processing symposium (IPDPS). IEEE, pp 885–895

  19. Epskamp S, Borsboom D, Fried EI (2018) Estimating psychological networks and their accuracy: a tutorial paper. Behav Res Methods 50:195–212

    Article  PubMed  Google Scholar 

  20. Epskamp S, Cramer AO, Waldorp LJ, Schmittmann VD, Borsboom D (2012) Qgraph: Network visualizations of relationships in psychometric data. J Stat Softw 48:1–18

    Article  Google Scholar 

  21. Friedman J, Hastie T, Tibshirani R (2008) Sparse inverse covariance estimation with the graphical lasso. Biostatistics 9:432–441

    Article  PubMed  Google Scholar 

  22. Haslbeck JM, Waldorp LJ (2015) Mgm: Structure estimation for time-varying mixed graphical models in high-dimensional data. Preprint at ar**v:1510.06871

  23. Jones HJ, Stergiakouli E, Tansey KE, Hubbard L, Heron J, Cannon M, Holmans P, Lewis G, Linden DEJ, Jones PB, Davey Smith G, O’Donovan MC, Owen MJ, Walters JT, Zammit S (2016) Phenotypic manifestation of genetic risk for schizophrenia during adolescence in the general population. JAMA Psychiat 73:221–228

    Article  Google Scholar 

  24. French L, Gray C, Leonard G, Perron M, Pike GB, Richer L, Séguin JR, Veillette S, Evans CJ, Artiges E, Banaschewski T, Bokde AWL, Bromberg U, Bruehl R, Buchel C, Cattrell A, Conrod PJ, Flor H, Frouin V, Gallinat J, Garavan H, Gowland P, Heinz A, Lemaitre H, Martinot J-L, Nees F, Orfanos DP, Pangelinan MM, Poustka L, Rietschel M, Smolka MN, Walter H, Whelan R, Timpson NJ, Schumann G, Smith GD, Pausova Z, Paus T (2015) Early cannabis use, polygenic risk score for schizophrenia and brain maturation in adolescence. JAMA Psychiat 72:1002–1011

    Article  Google Scholar 

Download references

Funding

The study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (X-2202-737-902). This research was conducted using the UK Biobank Resource under Application Number 33002. This study was supported by a National Research Foundation of Korea grant funded by the Ministry of Science and Information and Communication Technologies, South Korea (grant numbers NRF-2021R1A2C4001779 to WM and NRF-2022R1A2C2009998 to H-HW).

Author information

Authors and Affiliations

Authors

Contributions

WM and H–HW had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: WM and H–HW. Statistical analysis: WM and HK. Interpretation of data: all authors. Drafting of the manuscript: HKI, WM and HK. Revising of the manuscript: all authors. Study supervision: WM and H–HW.

Corresponding authors

Correspondence to Hong-Hee Won or Woojae Myung.

Ethics declarations

Conflict of interest

Woong-Yang Park was employed by a commercial company, GENINUS. Other authors state that they have no competing interests to declare.

Ethical approval

These funding sources were not involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1132 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ihm, H.K., Kim, H., Kim, J. et al. Genetic network structure of 13 psychiatric disorders in the general population. Eur Arch Psychiatry Clin Neurosci (2023). https://doi.org/10.1007/s00406-023-01601-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00406-023-01601-1

Keywords

Navigation