A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus.
Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
Gateva
Vesela
V
Sandling
Johanna K
JK
Hom
Geoff
G
Taylor
Kimberly E
KE
Chung
Sharon A
SA
Sun
Xin
X
Ortmann
Ward
W
Kosoy
Roman
R
Ferreira
Ricardo C
RC
Nordmark
Gunnel
G
Gunnarsson
Iva
I
Svenungsson
Elisabet
E
Padyukov
Leonid
L
Sturfelt
Gunnar
G
Jönsen
Andreas
A
Bengtsson
Anders A
AA
Rantapää-Dahlqvist
Solbritt
S
Baechler
Emily C
EC
Brown
Elizabeth E
EE
Alarcón
Graciela S
GS
Edberg
Jeffrey C
JC
Ramsey-Goldman
Rosalind
R
McGwin
Gerald
G
Reveille
John D
JD
Vilá
Luis M
LM
Kimberly
Robert P
RP
Manzi
Susan
S
Petri
Michelle A
MA
Lee
Annette
A
Gregersen
Peter K
PK
Seldin
Michael F
MF
Rönnblom
Lars
L
Criswell
Lindsey A
LA
Syvänen
Ann-Christine
AC
Behrens
Timothy W
TW
Graham
Robert R
RR
D056970:Co-Repressor Proteins; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C430460:JAZF1 protein, human; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C117046:TNIP1 protein, human; D016753:Interleukin-10; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1