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Review
. 2017 Apr 27;18(1):76.
doi: 10.1186/s13059-017-1207-1.

The MHC locus and genetic susceptibility to autoimmune and infectious diseases

Vasiliki Matzaraki  1 , Vinod Kumar  1 , Cisca Wijmenga  2   3 , Alexandra Zhernakova  1
Affiliations
Review

The MHC locus and genetic susceptibility to autoimmune and infectious diseases

Vasiliki Matzaraki et al. Genome Biol. .

Abstract

In the past 50 years, variants in the major histocompatibility complex (MHC) locus, also known as the human leukocyte antigen (HLA), have been reported as major risk factors for complex diseases. Recent advances, including large genetic screens, imputation, and analyses of non-additive and epistatic effects, have contributed to a better understanding of the shared and specific roles of MHC variants in different diseases. We review these advances and discuss the relationships between MHC variants involved in autoimmune and infectious diseases. Further work in this area will help to distinguish between alternative hypotheses for the role of pathogens in autoimmune disease development.

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Figures

Fig. 1
Fig. 1
Major histocompatibility complex imputation. A reference cohort of subjects for whom both genetic information and classic human leukocyte antigen (HLA) typing is available can be used to infer the missing (untyped) genotypes and amino acids in a discovery cohort. This allows imputed variants to be tested for their associations with a disease of interest. The figure shows imputation points to classic alleles associated with celiac disease risk in the MHC region on chromosome 6. Y tyrosine, S serine, Q glutamine, T threonine, R arginine, E glutamic acid
Fig. 2
Fig. 2
Major histocompatibility complex allele associations with autoimmune and infectious diseases. a Abbreviations marked with an asterisk indicate the autoimmune disease showing the strongest association with the specific locus. b Single nucleotide polymorphisms (SNPs) and alleles in the major histocompatibility complex (MHC) shared between autoimmune and infectious diseases. The blue area shows MHC alleles located in the class I region and the green area shows those in the class II region. The blue arrows indicate either a protective effect of the genetic variants against the infectious disease or a slower progression to the infectious disease. The red arrows indicate increased susceptibility to the corresponding autoimmune or infectious disease. AIDS acquired immunodeficiency syndrome, AS ankylosing spondylitis, CD Crohn’s disease, CeD celiac disease, DM dermatomyositis, HBV hepatitis B virus, HCV hepatitis C virus, HIV human immunodeficiency virus, MS multiple sclerosis, Ps psoriasis, RA rheumatoid arthritis, SLE systemic lupus erythematosus, T1D type 1 diabetes, TB tuberculosis, UC ulcerative colitis, HPV human papilloma virus
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