Table 1.
Associated pathway | Reported locus/gene | Reported odds ratio | Population | Comments/potential function | Ref. |
---|---|---|---|---|---|
TLR and type I IFN signaling | IRF5/TNPO3† | 1.3–2.0 | Asian, European | Transcription of IFN-α and IFN-α-induced genes | [65,79,84,130,131] |
PHRF1 (KIAA1542)/IRF7† | 1.3 | European, African–American | Associated variant in linkage with IRF7, which is involved in production of IFN-α | [65,84] | |
IRF8 | 1.2 | European, African–American | Downstream non-MyD88 dependent signals from TLRs | [68,73] | |
TYK2‡ | 1.1 | European | Initiates signaling cascades of a large number of cytokine receptors | [17,126–127] | |
IFIH1 | 1.2 | European, African–American | Sensing of intracellular nucleic acid, induces IFN-α and IFN-α-induced genes | [119,120] | |
TREX1‡ | Rare, high penetrance | European, African–American | DNA degradation as a 3′–5′ exonuclease, high IFN observed in the monogenic syndrome | [132] | |
SPP1 (OPN) | 1.3 | European, African–American | Gene encoding the cytokine OPN, interacts with IFN-α pathway | [100,108,110] | |
NF-κB signaling | TNIP1† | 1.3 | Asian, European | Interacts with TNFAIP3 and can act as a negative regulator of the NF-κB pathway downstream of TNF-α, has a key role in modulating cell activation, cytokine signaling and apoptosis | [78,79,131] |
TNFAIP3† | 1.7–2.7 | Asian, European | Termination of immune responses by protein ubiquitination | [79,80,131] | |
HIC2/UBE2L3‡ | 1.4 | Asian, European | Ubiquitination of NF-κB precursor p105 | [79,84,131] | |
SLC15A4‡ | 1.4 | Asian | Involved in Nod1-dependent NF-κB signaling, with potential participation in the antigen presentation in immune response | [79,131] | |
TLR/type I IFN, NF-κB and T-cell signaling | IRAK1‡ | 1.2 | European | Critical for TLR-7 and -9 signaling | [133,134] |
STAT4† | 1.5–1.8 | Asian, European, African–American | Downstream responses to IFN-α and other cytokine signals | [65,78–80,130,131] | |
T-cell function and signaling | PTPN22† | 1.3 | European | Modulation of lymphocyte activation and cytokine profile | [65,78] [65,79,131] |
TNFSF4† | 1.4–1.5 | Asian, European | Involved in T-cell/antigen-presenting cell interactions | ||
CD80†§ | 1.3 | Asian | T-cell proliferation and cytokine production | [131] | |
CDKN1B†§ | 1.2 | Asian | Inhibition of T-lymphocytes cell cycle progression | [131] | |
PDCD1 | 1.2 | European | Involved in lymphocyte signaling | [135] | |
B-cell function and signaling | BLK/FAM167A/XKR6† | 1.3–1.5 | Asian, European, African–American | Modulation of B-cell activation | [65,79,80,130,131] |
BANK1† | 1.4 | Asian, European | Modulation of B-cell activation | [131,136] | |
PRDM1† | 1.3 | Asian, European | Repressor of IFN-β gene expression; lymphocyte signaling | [78,79] | |
ETS1† | 1.3–1.5 | Asian | Regulate the development, senescence and death of many immune cells and that play a role in innate and adaptive immune response | [79,91,131] | |
IKZF1† | 1.2–1.4 | Asian | Regulates lymphocyte differentiation and proliferation, as well as self-tolerance through regulation of B-cell receptor signaling | [79] | |
RASGRP3‡ | 1.4 | Asian | Responsible for Ras-ERK signaling mediated by B-cell receptor ligation and might be involved in immunoglobulin production and B-cell proliferation | [79,131] | |
ARID5B†§ | 1.2 | Asian | Growth and differentiation of B-lymphocyte progenitors and other lymphocytes | [131] | |
T- and B-cell function and signaling | HLA region† | 1.4–2.4 | Asian, European, | Multiple immune system genes contained within this locus | [65,79,84,130,131] |
HLA-DQA1,HLA-DQA2, | African–American | ||||
HLA-DR3 and HLA-DRB1 | |||||
AFF1†§ | 1.2 | Asian | Important role in helper T cells and B cells, essential for normal lymphocyte development | [137] | |
Immune complex processing and hagocytosis | Early complement proteins (C1Q, C2, C4A and C4B) | All >2 | Rare variants of these genes show high penetrance for systemic lupus erythematosus | [9–12] | |
FcGR2A† | 1.4 | European, African–American | Clearance of immune complexes | [65,138] | |
FcGR3A | 1.6 | European | Clearance of immune complexes | [138] | |
CRP | 1.3 | European | Clearance of immune complexes | ||
Cellular adhesion; neutrophil, monocyte function and signaling | ITGAM/ITGAX† | 1.3–1.9 | Asian, European, African–American | Facilitates leukocyte adhesion to endothelial cells | [65,78,80,130,131] |
Apoptosis | ATG5† | 1.3 | Asian, European | Required for autophagy | [65,78,79,131] |
DRAM1† | 1.2 | Asian | Induction of autophagy and apoptosis and target of TP53 | [131] | |
DNA methylation | MECP2 | 1.2 | European | Found on X chromosome, involved in DNA methylation | [134,139,140] |
TET3, DGUOK† | 1.3 | Asian | Important in DNA demethylation | [131] | |
Other/unknown immune function | PXK† | 1.3 | European | [65] | |
WDFY4/LRRC18† | 1.2–1.5 | Asian, European | [79,80,91,131] | ||
UHRF1BP1† | 1.6 | European | [78] | ||
JAZF1†§ | 1.2 | European | Unknown function currently | [78] | |
TREH–DDX6†§ | 1.3 | Asian | [79,131] | ||
GPR19† | 1.3 | Asian | [130] |
Confirmed association with p < 10−7.
Confirmed association with p < 10−5.
Have not been replicated independently.
IFN: Interferon; TLR: Toll-like receptor.