TY - JOUR
T1 - Immunity and mental illness
T2 - findings from a Danish population-based immunogenetic study of seven psychiatric and neurodevelopmental disorders
AU - Nudel, Ron
AU - Benros, Michael E
AU - Krebs, Morten Dybdahl
AU - Allesøe, Rosa Lundbye
AU - Lemvigh, Camilla Koldbæk
AU - Bybjerg-Grauholm, Jonas
AU - Børglum, Anders D
AU - Daly, Mark J
AU - Nordentoft, Merete
AU - Mors, Ole
AU - Hougaard, David M
AU - Mortensen, Preben Bo
AU - Buil, Alfonso
AU - Werge, Thomas
AU - Rasmussen, Simon
AU - Thompson, Wesley K
N1 - Correction: Immunity and mental illness: findings from a Danish population-based immunogenetic study of seven psychiatric and neurodevelopmental disorder
https://doi.org/10.1038/s41431-019-0402-9
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1038/s41431-019-0402-9
DO - 10.1038/s41431-019-0402-9
M3 - Journal article
C2 - 30976114
VL - 27
SP - 1445
EP - 1455
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
ER -