An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes
Open accessAbstract
Importance: Certain psychiatric and immune-related disorders are reciprocal risk factors. However, the nature of these associations is unclear. Objective: To characterize the pleiotropy between psychiatric and immune-related traits, as well as risk factors of hypothesized relevance. Design, Setting, and Participants: This genetic association study was conducted from July 10, 2020, to January 15, 2022. Analyses used genome-wide association (GWA) statistics related to 14 psychiatric traits; 13 immune-related phenotypes, ie, allergic, autoimmune, and inflammatory disorders; and 15 risk factors related to health-related behaviors, social determinants of health, and stress response. Genetically correlated psychiatric-immune pairs were assessed using 2-sample mendelian randomization (MR) with sensitivity analyses and multivariable adjustment for genetic associations of third variables. False discovery rate correction (Q value < .05) was applied for each analysis. Exposures: Genetic associations. Main Outcomes and Measures: Genetic correlations and MR association estimates with SEs and P values. A data-driven approach was used that did not test a priori planned hypotheses. Results: A total of 44 genetically correlated psychiatric-immune pairs were identified, including 31 positive correlations (most consistently involving asthma, Crohn disease, hypothyroidism, and ulcerative colitis) and 13 negative correlations (most consistently involving allergic rhinitis and type 1 diabetes). Correlations with third variables were especially strong for psychiatric phenotypes. MR identified 7 associations of psychiatric phenotypes on immune-related phenotypes that were robust to multivariable adjustment, including the positive association of (1) the psychiatric cross-disorder phenotype with asthma (odds ratio [OR], 1.04; 95% CI, 1.02-1.06), Crohn disease (OR, 1.09; 95% CI, 1.05-1.14), and ulcerative colitis (OR, 1.09; 95% CI, 1.05-1.14); (2) major depression with asthma (OR, 1.25; 95% CI, 1.13-1.37); (3) schizophrenia with Crohn disease (OR, 1.12; 95% CI, 1.05-1.18) and ulcerative colitis (OR, 1.14; 95% CI, 1.07-1.21); and a negative association of risk tolerance with allergic rhinitis (OR, 0.77; 95% CI, 0.67-0.92). Conclusions and Relevance: Results of this genetic association study suggest that genetic liability for psychiatric disorders was associated with liability for several immune disorders, suggesting that vertical pleiotropy related to behavioral traits (or correlated third variables) contributes to clinical associations observed in population-scale data.
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MDD was positively correlated with Crohn's disease, ulcerative colitis, hyperthyroidism and asthma (Z-scores: 0.09-0.19, q<0.05).
“MDD was positively correlated with Crohn's disease, ulcerative colitis, hyperthyroidism and asthma (Z-scores: 0.09-0.19, q<0.05)213.”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [213]
The Results and Discussion report positive genetic correlations involving MDD and immune-related conditions, particularly asthma, Crohn disease, and ulcerative colitis (page not specified). The Results name hypothyroidism, not hyperthyroidism, and do not report the claimed Z-score range of 0.09–0.19 for these pairs; they do report an FDR Q threshold below 0.05. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe most robust association was observed for asthma (OR: 1.25, 95% CI: 1.13-1.37).
“The most robust association was observed for asthma (OR: 1.25, 95% CI: 1.13-1.37)213.”
From Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management (2023) · cites this paper as [213]
The Results report the stated OR and confidence interval for the association of major depression with asthma, among associations robust to multivariable adjustment. The citing sentence omits that the estimate is specific to major depression and calls it the “most robust” association, a ranking the cited Results do not state. (LLM, conf=0.85)
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Self-citation
- Authors
- Tylee, D. S., Lee, Y. K., Wendt, F. R., Pathak, G. A., Levey, D. F., De Angelis, F., Gelernter, J., & Polimanti, R.
- Affiliations
- Yale University (US)
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2022-07-01
- Volume
- 79
- Issue
- 7
- Pages
- 667
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC9069342
- OpenAlex
- W4225413432
- Cited by
- 65
- References
- 64
- Citations by year
- 2026: 21 · 2025: 11 · 2024: 15 · 2023: 17 · 2022: 1
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Funders
- National Institutes of Health (UL1TR001863)
- National Institute of Mental Health (F32MH122058, T32MH019961)
- National Institute on Drug Abuse (R33DA047527)
- National Institute on Deafness and Other Communication Disorders (R21DC018098)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- genetic correlation, mental illness, pleiotropy, asthma, Crohn's disease, ulcerative colitis, major depressive disorder, schizophrenia, allergic rhinitis, type 1 diabetes, autoimmune disease, inflammatory diseases, stress response, social determinants of health, health behavior, genetic risk factors
- MeSH terms
- Asthma, Colitis, Ulcerative, Crohn Disease, Humans, Phenotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Rhinitis, Allergic
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