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

被引：114

作者：

Bell, Steven ^{[1
,2
]}

Rigas, Andreas S. ^{[3
]}

Magnusson, Magnus K. ^{[4
,5
]}

Ferkingstad, Egil ^{[4
]}

Allara, Elias ^{[1
,2
]}

Bjornsdottir, Gyda ^{[4
]}

Ramond, Anna ^{[1
,2
,6
]}

Sorensen, Erik ^{[3
]}

Halldorsson, Gisli H. ^{[4
]}

Paul, Dirk S. ^{[1
,2
]}

Eggertsson, Hannes P. ^{[4
]}

Burgdorf, Kristoffer S. ^{[3
]}

Howson, Joanna M. M. ^{[2
]}

Thorner, Lise W. ^{[3
]}

Kristmundsdottir, Snaedis ^{[4
]}

Astle, William J. ^{[1
,2
,7
,8
]}

Erikstrup, Christian ^{[9
]}

Sigurdsson, Jon K. ^{[4
]}

Vuckovic, Dragana ^{[1
,8
]}

Dinh, Khoa M. ^{[9
]}

Tragante, Vinicius ^{[4
,10
]}

Surendran, Praveen ^{[2
,11
]}

Pedersen, Ole B. ^{[12
]}

Vidarsson, Brynjar ^{[13
]}

Jiang, Tao ^{[1
,2
,8
]}

Paarup, Helene M. ^{[14
]}

Onundarson, Pall T. ^{[5
,15
]}

Akbari, Parsa ^{[1
,2
,8
]}

Nielsen, Kaspar R. ^{[16
]}

Lund, Sigrun H. ^{[4
]}

Juliusson, Kristinn ^{[4
]}

Magnusson, Magnus, I ^{[4
]}

Frigge, Michael L. ^{[4
]}

Oddsson, Asmundur ^{[4
]}

Olafsson, Isleifur ^{[17
]}

Kaptoge, Stephen ^{[1
,2
]}

Hjalgrim, Henrik ^{[18
]}

Runarsson, Gudmundur ^{[13
]}

Wood, Angela M. ^{[1
,2
]}

Jonsdottir, Ingileif ^{[4
,5
]}

Hansen, Thomas F. ^{[19
,20
,21
]}

Sigurdardottir, Olof ^{[22
]}

Stefansson, Hreinn ^{[4
]}

Rye, David ^{[23
,24
]}

Peters, James E. ^{[2
]}

Westergaard, David ^{[25
]}

Holm, Hilma ^{[4
]}

Soranzo, Nicole ^{[1
,8
,26
]}

Banasik, Karina ^{[25
]}

Thorleifsson, Gudmar ^{[4
]}

机构：

[1] Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England

[2] Univ Cambridge, British Heart Fdn Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England

[3] Copenhagen Univ Hosp, Dept Clin Immunol, Copenhagen, Denmark

[4] Amgen Inc, deCODE Genet, Reykjavik, Iceland

[5] Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland

[6] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, Dept Infect Dis Epidemiol, London, England

[7] Cambridge Inst Publ Hlth, Med Res Council Biostat Unit, Cambridge, England

[8] Wellcome Sanger Inst, Dept Human Genet, Wellcome Trust Genome Campus, Hinxton, England

[9] Aarhus Univ Hosp, Dept Clin Immunol, Aarhus, Denmark

[10] Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands

[11] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

[12] Naestved Hosp, Dept Clin Immunol, Naestved, Denmark

[13] RAM, Lab Mjodd, Reykjavik, Iceland

[14] Odense Univ Hosp, Dept Clin Immunol, Odense, Denmark

[15] Natl Univ Hosp Iceland, Dept Lab Hematol, Landspitali, Reykjavik, Iceland

[16] Aalborg Univ Hosp, Dept Clin Immunol, Aalborg, Denmark

[17] Natl Univ Hosp Iceland, Dept Clin Biochem, Landspitali, Reykjavik, Iceland

[18] Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark

[19] Rigshosp Glostrup, Danish Headache Ctr, Dept Neurol, Glostrup, Denmark

[20] Copenhagen Univ Hosp MHC Sct Hans, Inst Biol Psychiat, Roskilde, Denmark

[21] Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Copenhagen, Denmark

[22] Akureyri Hosp, Dept Clin Biochem, Akureyri, Iceland

[23] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA USA

[24] Emory Univ, Sch Med, Program Sleep, Atlanta, GA USA

[25] Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Translat Dis Syst Biol, Copenhagen, Denmark

[26] Univ Cambridge, Dept Haematol, Cambridge, England

[27] UK Natl Hlth Serv Blood & Transplant, Cambridge Biomed Campus, Cambridge, England

[28] John Radcliffe Hosp, Radcliffe Dept Med, Oxford, England

[29] John Radcliffe Hosp, Natl Hlth Serv Blood & Transplant, Oxford, England

[30] John Radcliffe Hosp, UK Natl Hlth Serv Blood & Transplant, Oxford OX3 9BQ, England

[31] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland

来源：

COMMUNICATIONS BIOLOGY | 2021年 / 4卷 / 01期

基金：

英国医学研究理事会; 英国经济与社会研究理事会;

关键词：

RESTLESS LEGS SYNDROME; MICROCYTIC ANEMIA; HEPCIDIN EXPRESSION; DEFICIENCY; VARIANTS; INFLAMMATION; MUTATIONS; FREQUENCY; DIAGNOSIS; OVERLOAD;

D O I：

10.1038/s42003-020-01575-z

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

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