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GWAS Study

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis.

Mayes MD, Bossini-Castillo L, Gorlova O et al.

24387989 PubMed ID
GWAS Study Type
11192 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

MM
Mayes MD
BL
Bossini-Castillo L
GO
Gorlova O
MJ
Martin JE
ZX
Zhou X
CW
Chen WV
AS
Assassi S
YJ
Ying J
TF
Tan FK
AF
Arnett FC
RJ
Reveille JD
GS
Guerra S
TM
Teruel M
CF
Carmona FD
GP
Gregersen PK
LA
Lee AT
LE
López-Isac E
OE
Ochoa E
CP
Carreira P
SC
Simeón CP
CI
Castellví I
GM
González-Gay MÁ
ZA
Zhernakova A
PL
Padyukov L
AM
Alarcón-Riquelme M
WC
Wijmenga C
BM
Brown M
BL
Beretta L
RG
Riemekasten G
WT
Witte T
HN
Hunzelmann N
KA
Kreuter A
DJ
Distler JH
VA
Voskuyl AE
SA
Schuerwegh AJ
HR
Hesselstrand R
NA
Nordin A
AP
Airó P
LC
Lunardi C
SP
Shiels P
VL
van Laar JM
HA
Herrick A
WJ
Worthington J
DC
Denton C
WF
Wigley FM
HL
Hummers LK
VJ
Varga J
HM
Hinchcliff ME
BM
Baron M
HM
Hudson M
PJ
Pope JE
FD
Furst DE
KD
Khanna D
PK
Phillips K
SE
Schiopu E
SB
Segal BM
MJ
Molitor JA
SR
Silver RM
SV
Steen VD
SR
Simms RW
LR
Lafyatis RA
FB
Fessler BJ
FT
Frech TM
AF
Alkassab F
DP
Docherty P
KE
Kaminska E
KN
Khalidi N
JH
Jones HN
MJ
Markland J
RD
Robinson D
BJ
Broen J
RT
Radstake TR
FC
Fonseca C
KB
Koeleman BP
MJ
Martin J
Chapter II

Abstract

Summary of the research findings

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.

574 European ancestry cases, 3,466 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

11192
Total Participants
GWAS
Study Type
Yes
Replicated
1,217 European ancestry cases, 5,935 European ancestry controls
Replication Participants
European
Ancestry
U.S., Spain, Sweden, Canada, Germany, Netherlands, U.K., Italy
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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Analysis In Progress

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