Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

B Benyamin; T Esko; JS Ried; A Radhakrishnan; SH Vermeulen; M Traglia; M Gogele; D Anderson; Linda Broer; C Podmore; JA Luan; Z Kutalik; S Sanna; Paulien Meer; T Tanaka; FD Wang; HJ Westra; L Franke; E Mihailov; L Milani; J Haldin; J Winkelmann; T Meitinger; J Thiery; A Peters; M Waldenberger; A Rendon; J Jolley; J Sambrook; LA Kiemeney; FC Sweep; CF Sala; C Schwienbacher; I Pichler; J Hui; Ayse Demirkan; Aaron Isaacs; Najaf Amin; M Steri; G Waeber; N (Niek) Verweij; JE Powell; DR Nyholt; AC Heath; PAF Madden; PM Visscher; MJ Wright; GW Montgomery; NG Martin; D Hernandez; S Bandinelli; P van der Harst; M Uda; P Vollenweider; RA Scott; C Langenberg; NJ Wareham; Cornelia Duijn; J Beilby; PP Pramstaller; AA Hicks; WH Ouwehand; K Oexle; C Gieger; A Metspalu; C Camaschella; D Toniolo; DW Swinkels; JB Whitfield

doi:10.1038/ncomms5926

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

B Benyamin, T Esko, JS Ried, A Radhakrishnan, SH Vermeulen, M Traglia, M Gogele, D Anderson, Linda Broer, C Podmore, JA Luan, Z Kutalik, S Sanna, Paulien Meer, T Tanaka, FD Wang, HJ Westra, L Franke, E Mihailov, L MilaniJ Haldin, J Winkelmann, T Meitinger, J Thiery, A Peters, M Waldenberger, A Rendon, J Jolley, J Sambrook, LA Kiemeney, FC Sweep, CF Sala, C Schwienbacher, I Pichler, J Hui, Ayse Demirkan, Aaron Isaacs, Najaf Amin, M Steri, G Waeber, N (Niek) Verweij, JE Powell, DR Nyholt, AC Heath, PAF Madden, PM Visscher, MJ Wright, GW Montgomery, NG Martin, D Hernandez, S Bandinelli, P van der Harst, M Uda, P Vollenweider, RA Scott, C Langenberg, NJ Wareham, Cornelia Duijn, J Beilby, PP Pramstaller, AA Hicks, WH Ouwehand, K Oexle, C Gieger, A Metspalu, C Camaschella, D Toniolo, DW Swinkels, JB Whitfield

Research output: Contribution to journal › Article › Academic › peer-review

119 Citations (Scopus)

Abstract

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P < 5 x 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

Original language	Undefined/Unknown
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5926
Publication status	Published - 2014

Access to Document

10.1038/ncomms5926

Cite this

Benyamin, B., Esko, T., Ried, JS., Radhakrishnan, A., Vermeulen, SH., Traglia, M., Gogele, M., Anderson, D., Broer, L., Podmore, C., Luan, JA., Kutalik, Z., Sanna, S., Meer, P., Tanaka, T., Wang, FD., Westra, HJ., Franke, L., Mihailov, E., ... Whitfield, JB. (2014). Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. Nature Communications, 5. https://doi.org/10.1038/ncomms5926

Benyamin, B ; Esko, T ; Ried, JS ; Radhakrishnan, A ; Vermeulen, SH ; Traglia, M ; Gogele, M ; Anderson, D ; Broer, Linda ; Podmore, C ; Luan, JA ; Kutalik, Z ; Sanna, S ; Meer, Paulien ; Tanaka, T ; Wang, FD ; Westra, HJ ; Franke, L ; Mihailov, E ; Milani, L ; Haldin, J ; Winkelmann, J ; Meitinger, T ; Thiery, J ; Peters, A ; Waldenberger, M ; Rendon, A ; Jolley, J ; Sambrook, J ; Kiemeney, LA ; Sweep, FC ; Sala, CF ; Schwienbacher, C ; Pichler, I ; Hui, J ; Demirkan, Ayse ; Isaacs, Aaron ; Amin, Najaf ; Steri, M ; Waeber, G ; Verweij, N (Niek) ; Powell, JE ; Nyholt, DR ; Heath, AC ; Madden, PAF ; Visscher, PM ; Wright, MJ ; Montgomery, GW ; Martin, NG ; Hernandez, D ; Bandinelli, S ; van der Harst, P ; Uda, M ; Vollenweider, P ; Scott, RA ; Langenberg, C ; Wareham, NJ ; Duijn, Cornelia ; Beilby, J ; Pramstaller, PP ; Hicks, AA ; Ouwehand, WH ; Oexle, K ; Gieger, C ; Metspalu, A ; Camaschella, C ; Toniolo, D ; Swinkels, DW ; Whitfield, JB. / Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. In: Nature Communications. 2014 ; Vol. 5.

@article{bf33b00ffa504fedbea70eaf407bad40,

title = "Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis",

abstract = "Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P < 5 x 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.",

author = "B Benyamin and T Esko and JS Ried and A Radhakrishnan and SH Vermeulen and M Traglia and M Gogele and D Anderson and Linda Broer and C Podmore and JA Luan and Z Kutalik and S Sanna and Paulien Meer and T Tanaka and FD Wang and HJ Westra and L Franke and E Mihailov and L Milani and J Haldin and J Winkelmann and T Meitinger and J Thiery and A Peters and M Waldenberger and A Rendon and J Jolley and J Sambrook and LA Kiemeney and FC Sweep and CF Sala and C Schwienbacher and I Pichler and J Hui and Ayse Demirkan and Aaron Isaacs and Najaf Amin and M Steri and G Waeber and Verweij, {N (Niek)} and JE Powell and DR Nyholt and AC Heath and PAF Madden and PM Visscher and MJ Wright and GW Montgomery and NG Martin and D Hernandez and S Bandinelli and {van der Harst}, P and M Uda and P Vollenweider and RA Scott and C Langenberg and NJ Wareham and Cornelia Duijn and J Beilby and PP Pramstaller and AA Hicks and WH Ouwehand and K Oexle and C Gieger and A Metspalu and C Camaschella and D Toniolo and DW Swinkels and JB Whitfield",

year = "2014",

doi = "10.1038/ncomms5926",

language = "Undefined/Unknown",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Benyamin, B, Esko, T, Ried, JS, Radhakrishnan, A, Vermeulen, SH, Traglia, M, Gogele, M, Anderson, D, Broer, L, Podmore, C, Luan, JA, Kutalik, Z, Sanna, S, Meer, P, Tanaka, T, Wang, FD, Westra, HJ, Franke, L, Mihailov, E, Milani, L, Haldin, J, Winkelmann, J, Meitinger, T, Thiery, J, Peters, A, Waldenberger, M, Rendon, A, Jolley, J, Sambrook, J, Kiemeney, LA, Sweep, FC, Sala, CF, Schwienbacher, C, Pichler, I, Hui, J, Demirkan, A, Isaacs, A, Amin, N, Steri, M, Waeber, G, Verweij, N, Powell, JE, Nyholt, DR, Heath, AC, Madden, PAF, Visscher, PM, Wright, MJ, Montgomery, GW, Martin, NG, Hernandez, D, Bandinelli, S, van der Harst, P, Uda, M, Vollenweider, P, Scott, RA, Langenberg, C, Wareham, NJ, Duijn, C, Beilby, J, Pramstaller, PP, Hicks, AA, Ouwehand, WH, Oexle, K, Gieger, C, Metspalu, A, Camaschella, C, Toniolo, D, Swinkels, DW & Whitfield, JB 2014, 'Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis', Nature Communications, vol. 5. https://doi.org/10.1038/ncomms5926

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis. / Benyamin, B; Esko, T; Ried, JS; Radhakrishnan, A; Vermeulen, SH; Traglia, M; Gogele, M; Anderson, D; Broer, Linda; Podmore, C; Luan, JA; Kutalik, Z; Sanna, S; Meer, Paulien; Tanaka, T; Wang, FD; Westra, HJ; Franke, L; Mihailov, E; Milani, L; Haldin, J; Winkelmann, J; Meitinger, T; Thiery, J; Peters, A; Waldenberger, M; Rendon, A; Jolley, J; Sambrook, J; Kiemeney, LA; Sweep, FC; Sala, CF; Schwienbacher, C; Pichler, I; Hui, J; Demirkan, Ayse; Isaacs, Aaron; Amin, Najaf; Steri, M; Waeber, G; Verweij, N (Niek); Powell, JE; Nyholt, DR; Heath, AC; Madden, PAF; Visscher, PM; Wright, MJ; Montgomery, GW; Martin, NG; Hernandez, D; Bandinelli, S; van der Harst, P; Uda, M; Vollenweider, P; Scott, RA; Langenberg, C; Wareham, NJ; Duijn, Cornelia; Beilby, J; Pramstaller, PP; Hicks, AA; Ouwehand, WH; Oexle, K; Gieger, C; Metspalu, A; Camaschella, C; Toniolo, D; Swinkels, DW; Whitfield, JB.

In: Nature Communications, Vol. 5, 2014.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

AU - Benyamin, B

AU - Esko, T

AU - Ried, JS

AU - Radhakrishnan, A

AU - Vermeulen, SH

AU - Traglia, M

AU - Gogele, M

AU - Anderson, D

AU - Broer, Linda

AU - Podmore, C

AU - Luan, JA

AU - Kutalik, Z

AU - Sanna, S

AU - Meer, Paulien

AU - Tanaka, T

AU - Wang, FD

AU - Westra, HJ

AU - Franke, L

AU - Mihailov, E

AU - Milani, L

AU - Haldin, J

AU - Winkelmann, J

AU - Meitinger, T

AU - Thiery, J

AU - Peters, A

AU - Waldenberger, M

AU - Rendon, A

AU - Jolley, J

AU - Sambrook, J

AU - Kiemeney, LA

AU - Sweep, FC

AU - Sala, CF

AU - Schwienbacher, C

AU - Pichler, I

AU - Hui, J

AU - Demirkan, Ayse

AU - Isaacs, Aaron

AU - Amin, Najaf

AU - Steri, M

AU - Waeber, G

AU - Verweij, N (Niek)

AU - Powell, JE

AU - Nyholt, DR

AU - Heath, AC

AU - Madden, PAF

AU - Visscher, PM

AU - Wright, MJ

AU - Montgomery, GW

AU - Martin, NG

AU - Hernandez, D

AU - Bandinelli, S

AU - van der Harst, P

AU - Uda, M

AU - Vollenweider, P

AU - Scott, RA

AU - Langenberg, C

AU - Wareham, NJ

AU - Duijn, Cornelia

AU - Beilby, J

AU - Pramstaller, PP

AU - Hicks, AA

AU - Ouwehand, WH

AU - Oexle, K

AU - Gieger, C

AU - Metspalu, A

AU - Camaschella, C

AU - Toniolo, D

AU - Swinkels, DW

AU - Whitfield, JB

PY - 2014

Y1 - 2014

N2 - Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P < 5 x 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

AB - Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P < 5 x 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

U2 - 10.1038/ncomms5926

DO - 10.1038/ncomms5926

M3 - Article

VL - 5

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -