Table 1

A summary of loci associated with systemic lupus erythematosus in one or more genome-wide association studies, a meta-analysis, and replication studies (P <1

Locus

Gene

Position

Variant

P value (significance)

OR (CI) effect(size)

Autoimmune disease association

Function


ITGAMa

Intergrin alpha M

16p11.2 (intronic)

rs9888739 (T)

1.61×10-23

1.62 (1.47-1.78)

Phagocytosis

FcγR

Fcγ receptors

Multiple(see text)

Multiple (see text)

Multiple (see text)

Multiple (see text)

UC

Phagocytosis

PRDM1-ATG5b

PR domain zinc finger protein 1-autophagy-related 5 homolog

6q21-q22.1 (intergenic)

rs548234 (G)

5.18×10-12

1.25 (1.17-1.33)

Autophagy and B-cell differentiation

TNFAIP3b

Tumor necrosis factor-alpha-induced protein

6q23 (exonic)

rs2230926 (C)

1.37×10-17

1.72 (1.52-1.94)

RA, CeID, UC, and PS

Ubiquitination

TNIP1e

TNFAIP3-interacting protein 1

5q32-q33.1 (intronic)

rs7708392 (C)

3.8×10-13

1.27 (1.10-1.35)

PS

UBE2L3b

Ubiquitin-conjugating enzyme E2L 3

22q11.2- q13.1 (upstream)

rs463426 (G)

1.48×10-16

0.78 (0.74-0.83)

CD, RA, and CeID

ETS1b

V-ETS avian erythroblastosis virus E26 oncogene homolog 1

11q23.3 (downstream)

rs6590330 (A)

1.77×10-25

1.37 (1.29-1.45)

RA

Lymphocyte development and activation

IKZF1b

IKAROS family zinc finger 1

7p12 (upstream)

rs4917014 (C)

2.75×10-23

1.23 (1.03-1.42)

CD44d

CD44

11p13 (upstream)

rs507230

3.98×10-12

0.71 (0.63-0.79)

BANK1c

B-cell sca3 old protein with ankyrin repeats 1

4q22-q24 (exonic)

rs10516487 (G)

3.7×10-10

1.38 (1.25-1.53)

RA

B-cell activation and signaling

BLKb

B lymphoid tyrosine kinase

8p23-p22 (upstream)

rs7812879 (A)

2.09×10-24

0.69 (0.64-0.74)

RA

LYNa

V-yes-1 Yamaguchi sarcoma viral-related oncogene homolog

8q13 (intronic)

rs7829816 (C)

5.40×10-9

0.77 (0.70-0.84)

RasGRP3b

RAS guanyl releasing protein 3 (calcium and DAG-regulated)

2p25.1-p24.1 (intronic)

rs13385731 (G)

1.25×10-15

0.70 (0.64-0.76)

NCF2f

Neutrophil cytosolic factor 2

1q25(intronic)

rs10911363 (T)

2.87×10-11

1.18 (1.10-1.30)

STAT4b

Signal transducer and activator of transcription 4

2q32.2-q 32.3 (intronic)

rs7574865 (A)

5.17×10-42

1.51 (1.43-1.61)

RA, IBD, T1D, and Sjögren's syndrome

T-cell development and signaling

PTPN22e

Protein tyrosine phosphatase non-receptor type 22

1p13 (exonic)

rs2476601 (A)

3.4×10-12

1.35 (1.24-1.47)

T1D and Graves' disease

TNFSF4b

Tumor necrosis factor (ligand) superfamily member 4

1q25 (upstream)

rs2205960 (A)

2.5×10-32

1.46 (1.37-1.56)

HLA-DRB1e

HLA class II histocompatibility antigen

6p21.3(downstream)

rs3135394 (G)

2.0×10-60

1.98 (1.84-2.14)

T1D, RA, CeID, IBD, and CD

Antigen presentation

SLC15A4b

Solute carrier family 15, member 4

12q24.32 (exonic)

rs10847697 (A)

3.54×10-11

1.26 (1.17-1.34)

IRF5e

Interferon regulatory factor 5

7q32(3' untranslated region)

rs2070197 (C)

5.8×10-24

1.88 (1.78-1.95)

Rheumatic disease and RA

Interferon regulation and production

IRF7a

Interferon regulatory factor 7

11p15.5(downstream)

rs4963128 (T)

3.0×10-10

0.78 (0.73-0.85)

T1D

IRF8f

Interferon regulatory factor 8

16q24.1 (downstream)

rs2280381 (A)

1.24×10-8

1.17 (1.10-1.24)

UC and MS

IFIH1f

Interferon-induced helicase C domain- containing protein 1

2q24 (exonic)

rs1990760 (T)

1.63×10-8

1.23 (1.09-1.39)

TYK2f

Tyrosine kinase 2

19p13.2(intronic)

rs280519 (A)

3.88×10-8

1.29 (1.15-1.47)

MS

LRRC18-

Leucine-rich repeat

10q11.22-q11.23

rs1913517 (A)

7.22×10-12

1.24 (1.17-1.32)

Unknown function

WDFY4b

containing 18-WD repeat and FYVE domain-containing protein 4

(intergenic)

PXKa

PX domain containing serine/threonine kinase

3p14.3(intronic)

rs6445975 (C)

7.10×10-9

1.25 (1.16-1.35)

RA

JAZF1e

Juxtaposed withanother zinc finger gene 1

7p15 (intronic)

rs849142 (T)

1.5×10-9

1.19 (1.13-1.26)

UHRF1BP1e

UHRF-binding protein 1

6q23(exonic)

rs11755393 (G)

2.2×10-8

1.17 (1.10-1.24)

XKR6a

XK, Kell blood group complex subunit- related family, member36

8p23.1(intronic)

rs6985109 (G)

2.51×10-11

1.23 (1.16-1.30)


Odds ratios (ORs) and confidence intervals (CIs) are noted with the primary function of each locus. The genome-wide association studies from which this table was generated were conducted by aHarley and colleagues [95] (1,846 systemic lupus erythematosus (SLE) women cases and 1,825 controls), bHan and colleagues [53] (1,047 Han Chinese cases and 1,205 controls), and cKozyrev and colleagues [59] (279 Swedish SLE cases and 515 controls). The meta-analysis study was conducted by dRamos and colleagues [58] (939 Caucasian cases and 3,398 controls). The replication studies were conducted by Han and colleagues [53] (3,152 Han Chinese cases and 7,050 controls), eGateva and colleagues [6] (1,963 cases and 4,329 controls), and fCunninghame Graham and colleagues [69] (870 UK SLE cases and 5,551 controls). All loci that have been reported to be associated with other autoimmune diseases - Crohn's disease (CD), celiac disease (CeID), irritable bowel syndrome (IBD), multiple sclerosis (MS), psoriasis (PS), rheumatoid arthritis (RA), type 1 diabetes (T1D), and ulcerative colitis (UC) - are also stated [58].

Guerra et al. Arthritis Research & Therapy 2012 14:211   doi:10.1186/ar3844