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.
Vesela
V
Gateva
Johanna K
JK
Sandling
Geoff
G
Hom
Kimberly E
KE
Taylor
Sharon A
SA
Chung
Xin
X
Sun
Ward
W
Ortmann
Roman
R
Kosoy
Ricardo C
RC
Ferreira
Gunnel
G
Nordmark
Iva
I
Gunnarsson
Elisabet
E
Svenungsson
Leonid
L
Padyukov
Gunnar
G
Sturfelt
Andreas
A
Jönsen
Anders A
AA
Bengtsson
Solbritt
S
Rantapää-Dahlqvist
Emily C
EC
Baechler
Elizabeth E
EE
Brown
Graciela S
GS
Alarcón
Jeffrey C
JC
Edberg
Rosalind
R
Ramsey-Goldman
Gerald
G
McGwin
John D
JD
Reveille
Luis M
LM
Vilá
Robert P
RP
Kimberly
Susan
S
Manzi
Michelle A
MA
Petri
Annette
A
Lee
Peter K
PK
Gregersen
Michael F
MF
Seldin
Lars
L
Rönnblom
Lindsey A
LA
Criswell
Ann-Christine
AC
Syvänen
Timothy W
TW
Behrens
Robert R
RR
Graham
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