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A large-scale investigation into the role of classical HLA loci in multiple types of severe infections, with a focus on overlaps with autoimmune and mental disorders

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@article{501c6cf61b7e434192db467d212b9745,
title = "A large-scale investigation into the role of classical HLA loci in multiple types of severe infections, with a focus on overlaps with autoimmune and mental disorders",
abstract = "BACKGROUND: Infections are a major disease burden worldwide. While they are caused by external pathogens, host genetics also plays a part in susceptibility to infections. Past studies have reported diverse associations between human leukocyte antigen (HLA) alleles and infections, but many were limited by small sample sizes and/or focused on only one infection.METHODS: We performed an immunogenetic association study examining 13 categories of severe infection (bacterial, viral, central nervous system, gastrointestinal, genital, hepatitis, otitis, pregnancy-related, respiratory, sepsis, skin infection, urological and other infections), as well as a phenotype for having any infection, and seven classical HLA loci (HLA-A, B, C, DPB1, DQA1, DQB1 and DRB1). Additionally, we examined associations between infections and specific alleles highlighted in our previous studies of psychiatric disorders and autoimmune disease, as these conditions are known to be linked to infections.RESULTS: Associations between HLA loci and infections were generally not strong. Highlighted associations included associations between DQB1*0302 and DQB1*0604 and viral infections (P = 0.002835 and P = 0.014332, respectively), DQB1*0503 and sepsis (P = 0.006053), and DQA1*0301 with {"}other{"} infections (a category which includes infections not included in our main categories e.g. protozoan infections) (P = 0.000369). Some HLA alleles implicated in autoimmune diseases showed association with susceptibility to infections, but the latter associations were generally weaker, or with opposite trends (in the case of HLA-C alleles, but not with alleles of HLA class II genes). HLA alleles associated with psychiatric disorders did not show association with susceptibility to infections.CONCLUSIONS: Our results suggest that classical HLA alleles do not play a large role in the etiology of severe infections. The discordant association trends with autoimmune disease for some alleles could contribute to mechanistic theories of disease etiology.",
keywords = "Alleles, Gene Frequency, Genetic Predisposition to Disease, HLA-A Antigens/genetics, HLA-DQ beta-Chains/genetics, HLA-DRB1 Chains/genetics, Haplotypes, Humans, Mental Disorders/genetics, Association study, Autoimmune disease, MHC, Infections, Psychiatric disorder, Immunogenetics, HLA",
author = "Ron Nudel and Alles{\o}e, {Rosa Lundbye} and Thompson, {Wesley K} and Thomas Werge and Simon Rasmussen and Benros, {Michael E}",
year = "2021",
month = dec,
doi = "10.1186/s12967-021-02888-1",
language = "English",
volume = "19",
pages = "230",
journal = "Annals of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - A large-scale investigation into the role of classical HLA loci in multiple types of severe infections, with a focus on overlaps with autoimmune and mental disorders

AU - Nudel, Ron

AU - Allesøe, Rosa Lundbye

AU - Thompson, Wesley K

AU - Werge, Thomas

AU - Rasmussen, Simon

AU - Benros, Michael E

PY - 2021/12

Y1 - 2021/12

N2 - BACKGROUND: Infections are a major disease burden worldwide. While they are caused by external pathogens, host genetics also plays a part in susceptibility to infections. Past studies have reported diverse associations between human leukocyte antigen (HLA) alleles and infections, but many were limited by small sample sizes and/or focused on only one infection.METHODS: We performed an immunogenetic association study examining 13 categories of severe infection (bacterial, viral, central nervous system, gastrointestinal, genital, hepatitis, otitis, pregnancy-related, respiratory, sepsis, skin infection, urological and other infections), as well as a phenotype for having any infection, and seven classical HLA loci (HLA-A, B, C, DPB1, DQA1, DQB1 and DRB1). Additionally, we examined associations between infections and specific alleles highlighted in our previous studies of psychiatric disorders and autoimmune disease, as these conditions are known to be linked to infections.RESULTS: Associations between HLA loci and infections were generally not strong. Highlighted associations included associations between DQB1*0302 and DQB1*0604 and viral infections (P = 0.002835 and P = 0.014332, respectively), DQB1*0503 and sepsis (P = 0.006053), and DQA1*0301 with "other" infections (a category which includes infections not included in our main categories e.g. protozoan infections) (P = 0.000369). Some HLA alleles implicated in autoimmune diseases showed association with susceptibility to infections, but the latter associations were generally weaker, or with opposite trends (in the case of HLA-C alleles, but not with alleles of HLA class II genes). HLA alleles associated with psychiatric disorders did not show association with susceptibility to infections.CONCLUSIONS: Our results suggest that classical HLA alleles do not play a large role in the etiology of severe infections. The discordant association trends with autoimmune disease for some alleles could contribute to mechanistic theories of disease etiology.

AB - BACKGROUND: Infections are a major disease burden worldwide. While they are caused by external pathogens, host genetics also plays a part in susceptibility to infections. Past studies have reported diverse associations between human leukocyte antigen (HLA) alleles and infections, but many were limited by small sample sizes and/or focused on only one infection.METHODS: We performed an immunogenetic association study examining 13 categories of severe infection (bacterial, viral, central nervous system, gastrointestinal, genital, hepatitis, otitis, pregnancy-related, respiratory, sepsis, skin infection, urological and other infections), as well as a phenotype for having any infection, and seven classical HLA loci (HLA-A, B, C, DPB1, DQA1, DQB1 and DRB1). Additionally, we examined associations between infections and specific alleles highlighted in our previous studies of psychiatric disorders and autoimmune disease, as these conditions are known to be linked to infections.RESULTS: Associations between HLA loci and infections were generally not strong. Highlighted associations included associations between DQB1*0302 and DQB1*0604 and viral infections (P = 0.002835 and P = 0.014332, respectively), DQB1*0503 and sepsis (P = 0.006053), and DQA1*0301 with "other" infections (a category which includes infections not included in our main categories e.g. protozoan infections) (P = 0.000369). Some HLA alleles implicated in autoimmune diseases showed association with susceptibility to infections, but the latter associations were generally weaker, or with opposite trends (in the case of HLA-C alleles, but not with alleles of HLA class II genes). HLA alleles associated with psychiatric disorders did not show association with susceptibility to infections.CONCLUSIONS: Our results suggest that classical HLA alleles do not play a large role in the etiology of severe infections. The discordant association trends with autoimmune disease for some alleles could contribute to mechanistic theories of disease etiology.

KW - Alleles

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - HLA-A Antigens/genetics

KW - HLA-DQ beta-Chains/genetics

KW - HLA-DRB1 Chains/genetics

KW - Haplotypes

KW - Humans

KW - Mental Disorders/genetics

KW - Association study

KW - Autoimmune disease

KW - MHC

KW - Infections

KW - Psychiatric disorder

KW - Immunogenetics

KW - HLA

UR - http://www.scopus.com/inward/record.url?scp=85107119082&partnerID=8YFLogxK

U2 - 10.1186/s12967-021-02888-1

DO - 10.1186/s12967-021-02888-1

M3 - Journal article

C2 - 34059071

VL - 19

SP - 230

JO - Annals of Translational Medicine

JF - Annals of Translational Medicine

SN - 1479-5876

IS - 1

M1 - 230

ER -

ID: 66788698