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Genetic Association...
Genetic Associations Between Stress-Related Disorders and Autoimmune Disease
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- Zeng, Yu (author)
- West China Biomedical Big Data Center, West China Hospital, Chengdu, China; Med-X Center for Informatics, Sichuan University, Chengdu, China
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- Suo, Chen (author)
- Department of Epidemiology and Ministry ofEducation Key Laboratory of Public Health Safety, School of Public Health,Fudan University, Shanghai
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- Yao, Shuyang (author)
- Karolinska Institutet
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- Lu, Donghao (author)
- Karolinska Institutet
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- Larsson, Henrik, 1975- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
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- D'Onofrio, Brian M. (author)
- Karolinska Institutet
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- Lichtenstein, Paul (author)
- Karolinska Institutet
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- Fang, Fang (author)
- Karolinska Institutet
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- Valdimarsdóttir, Unnur A. (author)
- Karolinska Institutet
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- Song, Huan (author)
- West China Biomedical Big Data Center, West China Hospital, Chengdu, China; Med-X Center for Informatics, Sichuan University, Chengdu, China ; Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland
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(creator_code:org_t)
- HighWire Press, 2023
- 2023
- English.
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In: American Journal of Psychiatry. - : HighWire Press. - 0002-953X .- 1535-7228. ; 180:4, s. 294-304
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Objective: Emerging evidence supports a bidirectional phenotypic association between stress-related disorders and autoimmune disease. However, the biological underpinnings remain unclear. Here, the authors examined whether and how shared genetics contribute to the observed phenotypic associations.Methods: Based on data from 4,123,631 individuals identified from Swedish nationwide registers, familial coaggregation of stress-related disorders (any disorder or posttraumatic stress disorder [PTSD]) and autoimmune disease were initially estimated in seven cohorts with different degrees of kinship. Polygenic risk score (PRS) analyses were then performed with individual-level genotyping data from 376,871 participants in the UK Biobank study. Finally, genetic correlation analyses and enrichment analyses were performed with genome-wide association study (GWAS) summary statistics.Results: Familial coaggregation analyses revealed decreasing odds of concurrence of stress-related disorders and autoimmune disease with descending kinship or genetic relatedness between pairs of relatives; adjusted odds ratios were 1.51(95% CI=1.09-2.07), 1.28 (95% CI=0.97-1.68), 1.16 (95% CI=1.14-1.18), and 1.01 (95% CI=0.98-1.03) for monozygotic twins, dizygotic twins, full siblings, and half cousins, respectively. Statistically significant positive asso-ciations were observed between PRSs of stress-related disorders and autoimmune disease, as well as between PRSs of autoimmune disease and stress-related disorders. GWAS summary statistics revealed a genetic correlation of 0.26 (95% CI=0.14-0. 38) between these two pheno-types and identified 10 common genes and five shared functional modules, including one module related to G-protein-coupled receptor pathways. Similar analyses performed for PTSD and specific autoimmune diseases (e.g., autoimmune thyroid disease) largely recapitulated the results of the main analyses.Conclusions: This study demonstrated familial coaggregation, genetic correlation, and common biological pathways between stress-related disorders and autoimmune disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Autoimmune Disease
- Familial Coaggregation Analyses
- Genetic Association
- Polygenic Risk Score
- Signaling Pathway
- Stress-Related Disorders
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Zeng, Yu
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Suo, Chen
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Yao, Shuyang
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Lu, Donghao
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Larsson, Henrik, ...
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D'Onofrio, Brian ...
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Lichtenstein, Pa ...
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Fang, Fang
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Valdimarsdóttir, ...
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Song, Huan
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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American Journal ...
- By the university
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Örebro University
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Karolinska Institutet