Infection Polygenic Factors Account for a Small Proportion of the Relationship Between Infections and Mental Disorders.

Autor: Shorter JR; Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark. Electronic address: johnrshorter@gmail.com., Meijsen J; Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Nudel R; Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Krebs M; Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Gådin J; Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Mikkelsen DH; Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Nogueira Avelar E Silva R; Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Benros ME; Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Thompson WK; Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; Population Neuroscience and Genetics Lab, University of California San Diego, San Diego, California; Division of Biostatistics and Department of Radiology, University of California San Diego, San Diego, California., Ingason A; Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Werge T; Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: Biological psychiatry [Biol Psychiatry] 2022 Aug 15; Vol. 92 (4), pp. 283-290. Date of Electronic Publication: 2022 Jan 24.
DOI: 10.1016/j.biopsych.2022.01.007
Abstrakt: Background: Several recent studies have suggested a role for infections in the development of mental disorders; however, the genetic contribution to this association is understudied.
Methods: We use the iPSYCH case-cohort genotyped sample (n = 65,534) and Danish health care registry data to study the genetic association between infections and mental disorders. To test the hypothesis that these associations are due to genetic pleiotropy, we estimated the genetic correlation between infection and mental disorders. Polygenic risk scores (PRSs) were used to assess whether genetic pleiotropy of infections and mental disorders was mediated by actual infection diagnoses.
Results: We observed that schizophrenia, attention-deficit/hyperactivity disorder, major depressive disorder, bipolar disorder, and posttraumatic stress disorder (r g ranging between 0.18 and 0.83), but not autism spectrum disorder and anorexia nervosa, were significantly genetically correlated with infection diagnoses. PRSs for infections were associated with modest increase in risk of attention-deficit/hyperactivity disorder, major depressive disorder, and schizophrenia in the iPSYCH case-cohort (hazard ratios = 1.04 to 1.10) but was not associated with risk of anorexia, autism, or bipolar disorder. Using mediation analysis, we show that infection diagnoses account for only a small proportion (6%-14%) of the risk for mental disorders conferred by infection PRSs.
Conclusions: Infections and mental disorders share a modest genetic architecture. Infection PRSs can predict risk of certain mental disorders; however, this effect is moderate. Finally, recorded infections partially explain the relationship between infection PRSs and mental disorders.
(Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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