PMID- 32534018
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20210530
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 91
DP  - 2021 Jan
TI  - Genetic factors underlying the bidirectional relationship between autoimmune and 
      mental disorders - Findings from a Danish population-based study.
PG  - 10-23
LID - S0889-1591(20)30079-9 [pii]
LID - 10.1016/j.bbi.2020.06.014 [doi]
AB  - BACKGROUND: Previous studies have indicated the bidirectionality between 
      autoimmune and mental disorders. However, genetic studies underpinning the 
      co-occurrence of the two disorders have been lacking. In this study, we examined 
      the potential genetic contribution to the association between autoimmune and 
      mental disorders and investigated the genetic basis of overall autoimmune 
      disease. METHODS: We used diagnostic information from patients with seven 
      autoimmune diseases and six mental disorders from the Danish population-based 
      case-cohort sample (iPSYCH2012). We explored the epidemiological association 
      using survival analysis and modelled the effect of polygenic risk scores (PRSs) 
      on autoimmune and mental diseases. Genetic factors were investigated using GWAS 
      and imputed HLA alleles in the iPSYCH cohort. RESULTS: Of 64,039 individuals, a 
      total of 43,902 (68.6%) were diagnosed with mental disorders and 1383 (2.2%) with 
      autoimmune diseases. There was a significant comorbidity between the two disease 
      classes (P = 2.67 x 10(-7), OR = 1.38, 95%CI = 1.22-1.56), with an overall 
      bidirectional association, wherein individuals with autoimmune diseases had an 
      increased risk of subsequent mental disorders (HR = 1.13, 95%CI: 1.07-1.21, 
      P = 7.95 x 10(-5)) and vice versa (HR = 1.27, 95%CI = 1.16-1.39, 
      P = 8.77 x 10(-15)). Adding PRSs to these adjustment models did not have an 
      impact on the associations. PRSs for autoimmune diseases were only slightly 
      associated with increased risk of mental disorders (HR = 1.01, 95%CI: 1.00-1.02, 
      p = 0.038), whereas PRSs for mental disorders were not associated with autoimmune 
      diseases overall. Our GWAS highlighted 12 loci on chromosome 6 (minimum 
      P = 2.74 x 10(-36), OR = 1.80, 95% CI: 1.64-1.96), which were implicated in gene 
      regulation through bioinformatic functional analyses, thereby identifying new 
      candidate genes for overall autoimmune disease. Moreover, we observed 20 human 
      leukocyte antigen (HLA) alleles strongly associated, either positively or 
      negatively, with overall autoimmune disease, but we did not find significant 
      evidence of their associations with overall mental disorders. A GWAS of a 
      comorbid diagnosis of an autoimmune disease and a mental disorder identified a 
      genome-wide significant locus on chromosome 7 as well (P = 1.43 x 10(-8), 
      OR = 10.65, 95%CI = 3.21-35.36). CONCLUSIONS: Our findings confirm the overall 
      comorbidity and bidirectionality between autoimmune diseases and mental disorders 
      and identify HLA genes which are significantly associated with overall autoimmune 
      disease. Additionally, we identified several new candidate genes for overall 
      autoimmune disease and ranked them based on their association with the 
      investigated diseases.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Liu, Xueping
AU  - Liu X
AD  - CORE-Copenhagen Research Centre for Mental Health, Mental Health Centre 
      Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; iPSYCH, The 
      Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark.
FAU - Nudel, Ron
AU  - Nudel R
AD  - iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 
      Denmark; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, 
      Mental Health Services Copenhagen, Roskilde, Denmark.
FAU - Thompson, Wesley K
AU  - Thompson WK
AD  - iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 
      Denmark; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, 
      Mental Health Services Copenhagen, Roskilde, Denmark; Department of Family 
      Medicine and Public Health, Division of Biostatistics, University of California, 
      San Diego, CA, USA.
FAU - Appadurai, Vivek
AU  - Appadurai V
AD  - iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 
      Denmark; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, 
      Mental Health Services Copenhagen, Roskilde, Denmark.
FAU - Schork, Andrew J
AU  - Schork AJ
AD  - iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 
      Denmark; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, 
      Mental Health Services Copenhagen, Roskilde, Denmark.
FAU - Buil, Alfonso
AU  - Buil A
AD  - iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 
      Denmark; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, 
      Mental Health Services Copenhagen, Roskilde, Denmark.
FAU - Rasmussen, Simon
AU  - Rasmussen S
AD  - Novo Nordisk Foundation Center for Protein Research, Faculty of Health and 
      Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Allesoe, Rosa L
AU  - Allesoe RL
AD  - Novo Nordisk Foundation Center for Protein Research, Faculty of Health and 
      Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Werge, Thomas
AU  - Werge T
AD  - iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 
      Denmark; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, 
      Mental Health Services Copenhagen, Roskilde, Denmark; Department of Clinical 
      Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 
      Copenhagen, Denmark.
FAU - Mors, Ole
AU  - Mors O
AD  - iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 
      Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
FAU - Borglum, Anders D
AU  - Borglum AD
AD  - iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 
      Denmark; Department of Biomedicine, Aarhus University and Centre for Integrative 
      Sequencing, iSEQ, Aarhus, Denmark; Aarhus Genome Center, Aarhus, Denmark.
FAU - Hougaard, David M
AU  - Hougaard DM
AD  - iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 
      Denmark; Center for Neonatal Screening, Department for Congenital Disorders, 
      Statens Serum Institut, Copenhagen, Denmark.
FAU - Mortensen, Preben B
AU  - Mortensen PB
AD  - iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 
      Denmark; National Center for Register-Based Research, Aarhus University, Aarhus, 
      Denmark.
FAU - Nordentoft, Merete
AU  - Nordentoft M
AD  - CORE-Copenhagen Research Centre for Mental Health, Mental Health Centre 
      Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; iPSYCH, The 
      Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; 
      Department of Clinical Medicine, Faculty of Health and Medical Sciences, 
      University of Copenhagen, Copenhagen, Denmark.
FAU - Benros, Michael E
AU  - Benros ME
AD  - CORE-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. Electronic address: 
      Michael.Eriksen.Benros@regionh.dk.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200611
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
SB  - IM
CIN - Brain Behav Immun. 2020 Oct;89:7-8. PMID: 32805391
EIN - Brain Behav Immun. 2021 Aug;96:307-308. PMID: 34052110
MH  - *Autoimmune Diseases/epidemiology/genetics
MH  - Comorbidity
MH  - Denmark/epidemiology
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Humans
MH  - *Mental Disorders/epidemiology/genetics
MH  - Polymorphism, Single Nucleotide
MH  - *Psychotic Disorders
OTO - NOTNLM
OT  - Autoimmune diseases
OT  - Bidirectionality
OT  - Comorbidity
OT  - Genome-wide association study
OT  - Human leukocyte antigen
OT  - Mental disorders
EDAT- 2020/06/14 06:00
MHDA- 2021/05/28 06:00
CRDT- 2020/06/14 06:00
PHST- 2020/01/17 00:00 [received]
PHST- 2020/06/03 00:00 [revised]
PHST- 2020/06/06 00:00 [accepted]
PHST- 2020/06/14 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2020/06/14 06:00 [entrez]
AID - S0889-1591(20)30079-9 [pii]
AID - 10.1016/j.bbi.2020.06.014 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2021 Jan;91:10-23. doi: 10.1016/j.bbi.2020.06.014. Epub 2020 
      Jun 11.