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Table 2 Major histocompatibility complex (MHC) associations and risks for infectious diseases identified by genome-wide association studies (GWAS)

From: The MHC locus and genetic susceptibility to autoimmune and infectious diseases

Phenotype Initial sample size Replication sample size Mapped / nearest gene SNPs P-value OR or beta Reference
HIV-1 viral set point Euro-CHAVI, 486 seroconverters 140 Caucasian patients HCP5/B*5701 rs2395029 9.36 × 10−12 NA [69]
HLA-C rs9264942 3.77 × 10−9 NA
HIV-1 control 2362 European ancestry cases NA HSPA1B-C6orf48
LOC105375015
LOC105375015
HCP5
HCP5
PSORS1C1
rs9368699
rs9264942
rs9264942
rs2395029
rs2395029
rs3815087
5.00 × 10–08
6.00 × 10–32
6.00 × 10–12
5.00 × 10–35
1.00 × 10–11
8.00 × 10–08
NA
NA
NA
NA
NA
NA
[70]
AIDS progression 275 seropositive non-progressors, 86 seropositive rapid progressors, 1352 seronegative controls, All Europeans See [69] HCP5 rs2395029 3.00 × 10–19   [73]
LOC105375015 rs10484554 6.00 × 10–08 NA
HIV-1 control 974 controllers (cases) and 2648 progressors (controls) multi ethnic (Europeans, African-Americans, and Hispanics) Untreated HIV-infected persons from Switzerland HLA-C rs9264942 2.8 × 10−35 2.9 [62]
HLA-B*57:01 rs2395029 9.7 × 10−26 5.3
MICA rs4418214 1.4 × 10−34 4.4
PSORS1C3 rs3131018 4.2 × 10−16 2.1
HLA-B rs2523608 8.9 × 10–20 2.6
Intergenic rs2255221 3.5 × 10–14 2.7
HLA-B rs2523590 1.7 × 10–13 2.4
HIV-1 susceptibility 6334 cases, 7247 controls (Europeans) NA MICA - LOC105375017 rs4418214 4.00 × 10–11 1.52 [72]
Chronic hepatitis B infection 786 Japanese cases, 2201 Japanese controls Japanese and Thai cohorts of 1300 cases and 2100 controls HLA-DPA1 rs3077 2.31 × 10–38 0.56 [80]
HLA-DPB1 rs9277535 6.34 × 10–39 0.57
Chronic hepatitis B infection 458 Japanese cases, 2056 Japanese controls Three independent Japanese cohorts (2209 cases and 4440 controls) HLA-DPA1 rs3077 1.28 × 10−61 1.98 [83]
HLA-DPB1 rs9277535 3.72 × 10−17 1.95
HLA-DQB1 rs2856718 4.41 × 10−10 1.59
HLA-DQB2 rs7453920 1.27 × 10−10 2.2
Chronic hepatitis B infection 400 cases, 1000 controls, Koreans 971 cases, 1938 controls Korean TCF19 rs1419881 1.00 × 10–18 1.37 [77]
EHMT2 rs652888 7.00 × 10–13 1.38
HLA-DQB1 - LOC102725019 rs2856718 2.00 × 10–24 1.6
HLA-DQB2 rs7453920 7.00 × 10–26 2
HLA-DPA1 rs3077 5.00 × 10–39 1.89
HLA-DPB1 rs9277535 4.00 × 10–40 1.89
Hepatitis B 951 carrier cases, 937 cleared controls, Han Chinese 4230 carrier cases, 3051 cleared controls, 2622 controls, Han Chinese HCG27 - HLA-C rs3130542 9.00 × 10–14 1.33 [76]
HLA-DQB2 rs7453920 5.00 × 10–37 1.8868
Chronic hepatitis B infection 321 cases, 304 controls, TaiwaneseHan Chinese 1302 cases, 761 controls, Taiwanese Han Chinese LOC102725019 - HLA-DQA2 rs9276370 2.00 × 10–12 1.95  
HLA-DQB2 rs7453920 7.00 × 10–15 2.31 [79]
HLA-DPB1 rs9277535 5.00 × 10–14 1.59
LOC105375021 rs9366816 3.00 × 10–10 1.43
HLA-DQB1 - HLA-DQA2; LOC102725019 - HLA-DQA2; LOC102725019 - HLA-DQA2; LOC102725019 - HLA-DQA2; HLA-DQB1 - HLA-DQA2; LOC102725019 - HLA-DQA2; LOC102725019 - HLA-DQA2; LOC102725019 - HLA-DQA2, HLA-DQB2; HLA-DQB2; HLA-DQB2; HLA-DQB2; HLA-DQB2; HLA-DQB2; HLA-DQB2; HLA-DQB2, HLA-DPB1; HLA-DPB1; HLA-DPB1; HLA-DPB1; HLA-DPB1; HLA-DPB1; HLA-DPB1; HLA-DPB1, LOC105375021; LOC105375021 rs9276370, rs7756516, rs7453920, rs9277535, rs9366816 1.00 × 10–12 1.49  
Chronic hepatitis B infection 2514 cases, 1130 controls, Chinese 6600 cases, 8127 controls, Chinese HCG27 - HLA-C rs2853953 5.00 × 10–20 1.47 [78]
CFB rs12614 1.00 × 10–34 1.89
NOTCH4 rs422951 5.00 × 10–16 1.27
HLA-DQB1 - LOC102725019 rs2856718 7.00 × 10–28 1.28
HLA-DQB2 rs7453920 1.00 × 10–60 2
HLA-DOA rs378352 1.00 × 10–23 1.26
HLA-DPA1 rs3077 1.00 × 10–53 1.45
HLA-DPB1 rs9277535 1.00 × 10–70 1.52
Chronic hepatitis B infection/progression 181 Japanese carriers, 184 Japanese healthy controls 256 carriers, 236 healthy controls (Japanese) and 344 carriers, 151 healthy controls (Korean) 3' UTR of HLA-DPB1 rs9277542 8.36 × 10–8 0.42 [81]
Chronic hepatitis C infection 1482 chronic cases, 919 spontaneously cleared cases, European, African, and mixed/other ancestry 461 chronic cases, 284 spontaneously cleared cases HLA-DQB1 - LOC102725019 rs4273729 5.00 × 10–17 1.59 [65]
Chronic hepatitis C infection 481 cases, 2963 controls, Japanese 5737 cases, 26,931 controls Japanese HLA-DQB1 - LOC102725019 rs9275572 4.00 × 10–16 1.27 [84]
HPV seropositivity 1286 lung cancer cases, 679 head and neck cancer cases, 811 kidney cancer cases, 2035 controls, European ancestry 1307 head and neck cancer cases, 1037 controls, Hispanic HLA-DQB1 - LOC102725019 rs9357152 1.00 × 10–14 2.02 [85]
Dengue shock syndrome 2008 child cases, 2018 child controls, Vietnamese 1737 child cases, 2,934 child controls, Vietnamese MICB rs3132468 4.00 × 10–11 1.34 [74]
Leprosy 706 cases, 1225 controls Han Chinese 3254 cases, 5955 controls, Chinese HLA-DRB1 - HLA-DQA1 rs602875 5.00 × 10–27 1.61 [88]
Leprosy 1548 cases, 2150 controls, 4362 controls with immune-related diseases,
Chinese ancestry
6765 cases, 9505 controls, Chinese ancestry HLA-DRB1 - HLA-DQA1 rs9271100 8.00 × 10–95 1.68 [87]
M. Tuberculosis infection 8162 cases, 277,643 controls, Icelanders 5530 Russian cases, 5607 Russian controls and 438 cases from Croatia, 1009 controls from Croatia HLA-DQA1, HLA-DRB1 rs557011 3.1 × 10−13 1.14 [67]
Pulmonary tuberculosis HLA-DQA1, HLA-DRB1 rs557011 5.8 × 10−12 1.25
Pulmonary tuberculosis HLA-DQA1, HLA-DRB1 rs9271378 2.5 × 10−12 0.78
M. Tuberculosis infection HLA-DQA1 rs9272785 9.3 × 10−9 1.14
Leishmaniasis (visceral) 989 cases, 1089 controls (Indians), 357 cases,
1613 unaffected relatives
(Brazilians)
951 cases, 990 controls, Indians HLA-DRB1 - HLA-DQA1 rs9271858 3.00E–17 1.41 [92]
  1. Only genome-wide significant single nucleotide polymorphisms (SNPs) are given (P > 5 × 10–8), which are located in the MHC region (chr6:28,477,797-33,448,354). Assembly GRCh37/hg19
  2. AIDS acquired immune deficiency syndrome, NA not applicable, OR odds ratio