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A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.

Bell S, Rigas AS, Magnusson MK et al.

33536631 PubMed ID
GWAS Study Type
246139 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

BS
Bell S
RA
Rigas AS
MM
Magnusson MK
FE
Ferkingstad E
AE
Allara E
BG
Bjornsdottir G
RA
Ramond A
SE
Sørensen E
HG
Halldorsson GH
PD
Paul DS
BK
Burgdorf KS
EH
Eggertsson HP
HJ
Howson JMM
TL
Thørner LW
KS
Kristmundsdottir S
AW
Astle WJ
EC
Erikstrup C
SJ
Sigurdsson JK
VD
Vuckovic D
DK
Dinh KM
TV
Tragante V
SP
Surendran P
PO
Pedersen OB
VB
Vidarsson B
JT
Jiang T
PH
Paarup HM
OP
Onundarson PT
AP
Akbari P
NK
Nielsen KR
LS
Lund SH
JK
Juliusson K
MM
Magnusson MI
FM
Frigge ML
OA
Oddsson A
OI
Olafsson I
KS
Kaptoge S
HH
Hjalgrim H
RG
Runarsson G
WA
Wood AM
JI
Jonsdottir I
HT
Hansen TF
SO
Sigurdardottir O
SH
Stefansson H
RD
Rye D
PJ
Peters JE
WD
Westergaard D
HH
Holm H
SN
Soranzo N
BK
Banasik K
TG
Thorleifsson G
OW
Ouwehand WH
TU
Thorsteinsdottir U
RD
Roberts DJ
SP
Sulem P
BA
Butterworth AS
GD
Gudbjartsson DF
DJ
Danesh J
BS
Brunak S
DA
Di Angelantonio E
UH
Ullum H
SK
Stefansson K
Chapter II

Abstract

Summary of the research findings

Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.

246,139 European ancestry individuals

Chapter III

Study Statistics

Key metrics and study information

246139
Total Participants
GWAS
Study Type
No
Replicated
European
Ancestry
Denmark, Iceland, U.K.
Recruitment Country
Chapter IV

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