Preben Bo Mortensen

Immunity and mental illness: findings from a Danish population-based immunogenetic study of seven psychiatric and neurodevelopmental disorders

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Dokumenter

DOI

  • Ron Nudel, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
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  • Michael E Benros, Copenhagen University Hospital, Mental Health Centre Copenhagen, Mental Health Services, Capital Region of Denmark, Copenhagen
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  • Morten Dybdahl Krebs, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
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  • Rosa Lundbye Allesøe, DTU Bioinformatics, Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, 2800 Kongens Lyngby, Denmark.
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  • Camilla Koldbæk Lemvigh, DTU Bioinformatics, Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, 2800 Kongens Lyngby, Denmark.
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  • Jonas Bybjerg-Grauholm, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark.
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  • Anders D Børglum
  • Mark J Daly, 1] Analytical and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA [2] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
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  • Merete Nordentoft, l Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
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  • Ole Mors
  • David M Hougaard, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark.
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  • Preben Bo Mortensen
  • Alfonso Buil, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
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  • Thomas Werge, l Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
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  • Simon Rasmussen, Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark. simon.rasmussen@cpr.ku.dk., Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. simon.rasmussen@cpr.ku.dk.
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  • Wesley K Thompson, Department of Family Medicine and Public Health, Division of Biostatistics, University of California, San Diego, CA, USA. wkthompson@ucsd.edu.

Human leukocyte antigen (HLA) genes encode proteins with important roles in the regulation of the immune system. Many studies have also implicated HLA genes in psychiatric and neurodevelopmental disorders. However, these studies usually focus on one disorder and/or on one HLA candidate gene, often with small samples. Here, we access a large dataset of 65,534 genotyped individuals consisting of controls (N = 19,645) and cases having one or more of autism spectrum disorder (N = 12,331), attention deficit hyperactivity disorder (N = 14,397), schizophrenia (N = 2401), bipolar disorder (N = 1391), depression (N = 18,511), anorexia (N = 2551) or intellectual disability (N = 3175). We imputed participants' HLA alleles to investigate the involvement of HLA genes in these disorders using regression models. We found a pronounced protective effect of DPB1*1501 on susceptibility to autism (p = 0.0094, OR = 0.72) and intellectual disability (p = 0.00099, OR = 0.41), with an increased protective effect on a comorbid diagnosis of both disorders (p = 0.003, OR = 0.29). We also identified a risk allele for intellectual disability, B*5701 (p = 0.00016, OR = 1.33). Associations with both alleles survived FDR correction and a permutation procedure. We did not find significant evidence for replication of previously-reported associations for autism or schizophrenia. Our results support an implication of HLA genes in autism and intellectual disability, which requires replication by other studies. Our study also highlights the importance of large sample sizes in HLA association studies.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Human Genetics
Vol/bind27
Nummer9
Sider (fra-til)1445-1455
Antal sider11
ISSN1018-4813
DOI
StatusUdgivet - sep. 2019

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