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GWAS Study

Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.

Kiryluk K, Li Y, Scolari F et al.

25305756 PubMed ID
GWAS Study Type
20612 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

KK
Kiryluk K
LY
Li Y
SF
Scolari F
SS
Sanna-Cherchi S
CM
Choi M
VM
Verbitsky M
FD
Fasel D
LS
Lata S
PS
Prakash S
SS
Shapiro S
FC
Fischman C
SH
Snyder HJ
AG
Appel G
IC
Izzi C
VB
Viola BF
DN
Dallera N
DV
Del Vecchio L
BC
Barlassina C
SE
Salvi E
BF
Bertinetto FE
AA
Amoroso A
SS
Savoldi S
RM
Rocchietti M
AA
Amore A
PL
Peruzzi L
CR
Coppo R
SM
Salvadori M
RP
Ravani P
MR
Magistroni R
GG
Ghiggeri GM
CG
Caridi G
BM
Bodria M
LF
Lugani F
AL
Allegri L
DM
Delsante M
MM
Maiorana M
MA
Magnano A
FG
Frasca G
BE
Boer E
BG
Boscutti G
PC
Ponticelli C
MR
Mignani R
MC
Marcantoni C
DL
Di Landro D
SD
Santoro D
PA
Pani A
PR
Polci R
FS
Feriozzi S
CS
Chicca S
GM
Galliani M
GM
Gigante M
GL
Gesualdo L
ZP
Zamboli P
BG
Battaglia GG
GM
Garozzo M
MD
Maixnerová D
TV
Tesar V
EF
Eitner F
RT
Rauen T
FJ
Floege J
KT
Kovacs T
NJ
Nagy J
MK
Mucha K
PL
Pączek L
ZM
Zaniew M
MM
Mizerska-Wasiak M
RM
Roszkowska-Blaim M
PK
Pawlaczyk K
GD
Gale D
BJ
Barratt J
TL
Thibaudin L
BF
Berthoux F
CG
Canaud G
BA
Boland A
MM
Metzger M
PU
Panzer U
SH
Suzuki H
GS
Goto S
NI
Narita I
CY
Caliskan Y
XJ
Xie J
HP
Hou P
CN
Chen N
ZH
Zhang H
WR
Wyatt RJ
NJ
Novak J
JB
Julian BA
FJ
Feehally J
SB
Stengel B
CD
Cusi D
LR
Lifton RP
GA
Gharavi AG
Chapter II

Abstract

Summary of the research findings

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.

1,194 Han Chinese ancestry cases, 902 Han Chinese ancestry controls, 1,553 European ancestry cases, 3,050 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

20612
Total Participants
GWAS
Study Type
Yes
Replicated
2,491 East Asian ancestry cases, 1,780 East Asian ancestry controls, 2,420 European ancestry cases, 7,222 European ancestry controls
Replication Participants
East Asian, European
Ancestry
China, Japan, Poland, Czech Republic, Italy, Turkey, Germany, U.K., Hungary, France, U.S.
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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Analysis In Progress

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