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GWAS Study

Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases.

Klarić L, Tsepilov YA, Stanton CM et al.

32128391 PubMed ID
GWAS Study Type
10478 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

KL
Klarić L
TY
Tsepilov YA
SC
Stanton CM
MM
Mangino M
ST
Sikka TT
ET
Esko T
PE
Pakhomov E
SP
Salo P
DJ
Deelen J
MS
McGurnaghan SJ
KT
Keser T
VF
Vučković F
UI
Ugrina I
KJ
Krištić J
GI
Gudelj I
ŠJ
Štambuk J
PR
Plomp R
PM
Pučić-Baković M
PT
Pavić T
VM
Vilaj M
TI
Trbojević-Akmačić I
DC
Drake C
DP
Dobrinić P
MJ
Mlinarec J
JB
Jelušić B
RA
Richmond A
TM
Timofeeva M
GA
Grishchenko AK
DJ
Dmitrieva J
BM
Bermingham ML
SS
Sharapov SZ
FS
Farrington SM
TE
Theodoratou E
UH
Uh HW
BM
Beekman M
SE
Slagboom EP
LE
Louis E
GM
Georges M
WM
Wuhrer M
CH
Colhoun HM
DM
Dunlop MG
PM
Perola M
FK
Fischer K
PO
Polasek O
CH
Campbell H
RI
Rudan I
WJ
Wilson JF
ZV
Zoldoš V
VV
Vitart V
ST
Spector T
AY
Aulchenko YS
LG
Lauc G
HC
Hayward C
Chapter II

Abstract

Summary of the research findings

Effector functions of immunoglobulin G (IgG) are regulated by the composition of a glycan moiety, thus affecting activity of the immune system. Aberrant glycosylation of IgG has been observed in many diseases, but little is understood about the underlying mechanisms. We performed a genome-wide association study of IgG N-glycosylation (N = 8090) and, using a data-driven network approach, suggested how associated loci form a functional network. We confirmed in vitro that knockdown of IKZF1 decreases the expression of fucosyltransferase FUT8, resulting in increased levels of fucosylated glycans, and suggest that RUNX1 and RUNX3, together with SMARCB1, regulate expression of glycosyltransferase MGAT3. We also show that variants affecting the expression of genes involved in the regulation of glycoenzymes colocalize with variants affecting risk for inflammatory diseases. This study provides new evidence that variation in key transcription factors coupled with regulatory variation in glycogenes modifies IgG glycosylation and has influence on inflammatory diseases.

8,090 European ancestry individuals

Chapter III

Study Statistics

Key metrics and study information

10478
Total Participants
GWAS
Study Type
Yes
Replicated
2,388 European ancestry individuals
Replication Participants
European
Ancestry
Chapter IV

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