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Genetic correlations among psychiatric and immune‐related phenotypes based on genome‐wide association data
Open accessAbstract
Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary‐level data from previous genome‐wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune‐related phenotypes. We estimated heritability and examined pair‐wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune‐related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit‐hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome‐wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune‐related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.
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“Shared genetic factors or familial causes of neurodevelopmental conditions and autoimmune disorders have also been identified286.”
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Metadata
- Authors
- Tylee, D. S., Sun, J., Hess, J. L., Tahir, M. A., Sharma, E., Malik, R., Worrall, B. B., Levine, A. J., Martinson, J. J., Nejentsev, S., Speed, D., Fischer, A., Mick, E., Walker, B. R., Crawford, A., Grant, S. F. A., Polychronakos, C., Bradfield, J. P., Sleiman, P. M. A., Hakonarson, H., Ellinghaus, E., Elder, J. T., Tsoi, L. C., Trembath, R. C., Barker, J. N., Franke, A., Dehghan, A., The 23 and Me Research Team, The Inflammation Working Group of the CHARGE Consortium, The METASTROKE Consortium of the International Stroke Genetics Consortium, The Netherlands Twin Registry, The neuroCHARGE Working Group, The Obsessive Compulsive and Tourette Syndrome Working Group of the Psychiatric Genomics Consortium, Faraone, S. V., & Glatt, S. J.
- Affiliations
- SUNY Upstate Medical University (US)
- LMU Klinikum (DE)
- University of Virginia (US)
- University of California, Los Angeles (US)
- University of Pittsburgh (US)
- University of Cambridge (GB)
- University College London (GB)
- Christian-Albrechts-Universität zu Kiel (DE)
- University of Massachusetts Chan Medical School (US)
- The Queen's Medical Research Institute (GB)
- University of Bristol (GB)
- Children's Hospital of Philadelphia (US)
- McGill University Health Centre (CA)
- Center for Applied Genomics, Division of Human Genetics The Children's Hospital of Philadelphia Philadelphia Pennsylvania
- University of Michigan (US)
- King's College London (GB)
- Institute of Clinical Molecular Biology Christian Albrechts University of Kiel Kiel Germany
- MRC Centre for Environment and Health (GB)
- Corresponding author
- Tylee, Daniel S.
- ORCID
- Tylee, Daniel S.
- Sun, Jiayin
- Hess, Jonathan L.
- Malik, Rainer
- Worrall, Bradford B.
- Levine, Andrew J.
- Martinson, Jeremy J.
- Nejentsev, Sergey
- Speed, Doug
- Mick, Eric
- Walker, Brian R.
- Crawford, Andrew
- Grant, Struan F. A.
- Polychronakos, Constantin
- Hakonarson, Hakon
- Ellinghaus, Eva
- Elder, James T.
- Tsoi, Lam C.
- Trembath, Richard C.
- Dehghan, Abbas
- Faraone, Stephen V.
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2018-10
- Volume
- 177
- Issue
- 7
- Pages
- 641-657
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC6230304
- OpenAlex
- W2897469060
- Cited by
- 219
- References
- 131
- Citations by year
- 2026: 14 · 2025: 24 · 2024: 24 · 2023: 27 · 2022: 52 · 2021: 28 · 2020: 24 · 2019: 19 · 2018: 5
- FWCI
- 11.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Bristol Research (University of Bristol) (acceptedVersion, other-oa)
- Explore Bristol Research (acceptedVersion, other-oa)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Autism Speaks (Weatherstone Pre‐doctoral Training Grant #9645; DS)
- Brain and Behavior Research Foundation (SJG)
- Gerber Foundation (SJG)
- National Alliance for Research on Schizophrenia and Depression (SJG)
- National Institutes of Health (R01MH101519, R01AG054002, P50MH081755 (SJG), R03DA)
- Sidney R. Baer, Jr. Foundation (SJG)
- Wellcome Trust (SN)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- genetic correlation, mental illness, autoimmune disease comorbidity, immune signaling, schizophrenia, Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, ulcerative colitis, anorexia nervosa, attention deficit hyperactivity disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, Tourette syndrome, smoking behavior, heritability, shared genetic loci
- MeSH terms
- Autoimmune Diseases, Mental Disorders, Female, Humans, Male, Linkage Disequilibrium, Comorbidity, Databases, Factual, Genetic Predisposition to Disease, Multifactorial Inheritance, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study
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