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

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  1. Reappraisal of variants previously linked with sudden infant death syndrome: results from three population-based cohorts

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  2. Haploinsufficiency of ARHGAP42 is associated with hypertension

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  3. Correction: Educational delay and attainment in persons with neurofibromatosis 1 in Denmark

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  4. The Global State of the Genetic Counseling Profession

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  5. Educational delay and attainment in persons with neurofibromatosis 1 in Denmark

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  1. Socio-demographic and clinical risk factors of treatment-resistant depression: A Danish population-based cohort study

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  2. Widespread higher fractional anisotropy associates to better cognitive functions in individuals at ultra-high risk for psychosis

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  3. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

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  4. Autism spectrum disorder and attention deficit hyperactivity disorder have a similar burden of rare protein-truncating variants

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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 : EJHG
Volume27
Issue number9
Pages (from-to)1445-1455
Number of pages11
ISSN1018-4813
DOIs
Publication statusPublished - Sep 2019

ID: 57522020