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

Research output: Contribution to journalJournal article – Annual report year: 2019Researchpeer-review

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  • Author: Nudel, Ron

    Mental Health Centre Sct. Hans, Denmark

  • Author: Benros, Michael E.

    The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark

  • Author: Krebs, Morten Dybdahl

    Mental Health Centre Sct. Hans, Denmark

  • Author: Allesøe, Rosa Lundbye

    Integrative Systems Biology, Bioinformatics, Department of Health Technology, Technical University of Denmark, Ørsteds Plads, DK-2800, Kgs. Lyngby, Denmark

  • Author: Lemvigh, Camilla Koldbæk

    Bioinformatics, Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Bybjerg-Grauholm, Jonas

    The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark

  • Author: Børglum, Anders D.

    The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark

  • Author: Daly, Mark J.

    The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark

  • Author: Nordentoft, Merete

    The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark

  • Author: Mors, Ole

    The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark

  • Author: Hougaard, David M.

    The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark

  • Author: Mortensen, Preben Bo

    The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark

  • Author: Buil, Alfonso

    Mental Health Centre Sct. Hans, Denmark

  • Author: Werge, Thomas

    Mental Health Centre Sct. Hans, Denmark

  • Author: Rasmussen, Simon

    Department of Health Technology, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Thompson, Wesley K.

    Mental Health Centre Sct. Hans, Denmark

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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.
Original languageEnglish
JournalEuropean journal of human genetics
Number of pages11
ISSN1018-4813
DOIs
Publication statusAccepted/In press - 2019

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© The Author(s) 2019. This article is published with open access

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