Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project

Donald J Lehmann; Maaike Schuur; Donald R Warden; Naomi Hammond; Olivia Belbin; Heike Kölsch; Michael G Lehmann; Gordon K Wilcock; Kristelle Brown; Patrick G Kehoe; Chris M Morris; Rachel Barker; Eliecer Coto; Victoria Alvarez; Panos Deloukas; Ignacio Mateo; Rhian Gwilliam; Onofre Combarros; Alejandro Arias-Vásquez; Yurii S Aulchenko; M Arfan Ikram; Monique M Breteler; Cornelia M van Duijn; Abderrahim Oulhaj; Reinhard Heun; Mario Cortina-Borja; Kevin Morgan; Kathryn Robson; A David Smith

doi:10.1016/j.neurobiolaging.2010.07.018

Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project

Donald J Lehmann, Maaike Schuur, Donald R Warden, Naomi Hammond, Olivia Belbin, Heike Kölsch, Michael G Lehmann, Gordon K Wilcock, Kristelle Brown, Patrick G Kehoe, Chris M Morris, Rachel Barker, Eliecer Coto, Victoria Alvarez, Panos Deloukas, Ignacio Mateo, Rhian Gwilliam, Onofre Combarros, Alejandro Arias-Vásquez, Yurii S AulchenkoM Arfan Ikram, Monique M Breteler, Cornelia M van Duijn, Abderrahim Oulhaj, Reinhard Heun, Mario Cortina-Borja, Kevin Morgan, Kathryn Robson, A David Smith

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Abstract

ron overload may contribute to the risk of Alzheimer's disease (AD). In the Epistasis Project, with 1757 cases of AD and 6295 controls, we studied 4 variants in 2 genes of iron metabolism: hemochromatosis (HFE) C282Y and H63D, and transferrin (TF) C2 and -2G/A. We replicated the reported interaction between HFE 282Y and TF C2 in the risk of AD: synergy factor, 1.75 (95% confidence interval, 1.1-2.8, p = 0.02) in Northern Europeans. The synergy factor was 3.1 (1.4-6.9; 0.007) in subjects with the APOEε4 allele. We found another interaction, between HFE 63HH and TF -2AA, markedly modified by age. Both interactions were found mainly or only in Northern Europeans. The interaction between HFE 282Y and TF C2 has now been replicated twice, in altogether 2313 cases of AD and 7065 controls, and has also been associated with increased iron load. We therefore suggest that iron overload may be a causative factor in the development of AD. Treatment for iron overload might thus be protective in some cases.

Translated title of the contribution	Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project
Original language	English
Pages (from-to)	e1 - 13
Number of pages	14
Journal	Neurobiology of Aging
Volume	33
Issue number	1
DOIs	https://doi.org/10.1016/j.neurobiolaging.2010.07.018
Publication status	Published - Jan 2012

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Cerebrovascular and Dementia Research Group

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Lehmann, D. J., Schuur, M., Warden, D. R., Hammond, N., Belbin, O., Kölsch, H., Lehmann, M. G., Wilcock, G. K., Brown, K., Kehoe, P. G., Morris, C. M., Barker, R., Coto, E., Alvarez, V., Deloukas, P., Mateo, I., Gwilliam, R., Combarros, O., Arias-Vásquez, A., ... Smith, A. D. (2012). Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project. Neurobiology of Aging, 33(1), e1 - 13. https://doi.org/10.1016/j.neurobiolaging.2010.07.018

@article{96d77dcae75041449056aa504888b4b2,

title = "Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project",

abstract = "ron overload may contribute to the risk of Alzheimer's disease (AD). In the Epistasis Project, with 1757 cases of AD and 6295 controls, we studied 4 variants in 2 genes of iron metabolism: hemochromatosis (HFE) C282Y and H63D, and transferrin (TF) C2 and -2G/A. We replicated the reported interaction between HFE 282Y and TF C2 in the risk of AD: synergy factor, 1.75 (95% confidence interval, 1.1-2.8, p = 0.02) in Northern Europeans. The synergy factor was 3.1 (1.4-6.9; 0.007) in subjects with the APOEε4 allele. We found another interaction, between HFE 63HH and TF -2AA, markedly modified by age. Both interactions were found mainly or only in Northern Europeans. The interaction between HFE 282Y and TF C2 has now been replicated twice, in altogether 2313 cases of AD and 7065 controls, and has also been associated with increased iron load. We therefore suggest that iron overload may be a causative factor in the development of AD. Treatment for iron overload might thus be protective in some cases.",

author = "Lehmann, {Donald J} and Maaike Schuur and Warden, {Donald R} and Naomi Hammond and Olivia Belbin and Heike K{\"o}lsch and Lehmann, {Michael G} and Wilcock, {Gordon K} and Kristelle Brown and Kehoe, {Patrick G} and Morris, {Chris M} and Rachel Barker and Eliecer Coto and Victoria Alvarez and Panos Deloukas and Ignacio Mateo and Rhian Gwilliam and Onofre Combarros and Alejandro Arias-V{\'a}squez and Aulchenko, {Yurii S} and Ikram, {M Arfan} and Breteler, {Monique M} and {van Duijn}, {Cornelia M} and Abderrahim Oulhaj and Reinhard Heun and Mario Cortina-Borja and Kevin Morgan and Kathryn Robson and Smith, {A David}",

year = "2012",

month = jan,

doi = "10.1016/j.neurobiolaging.2010.07.018",

language = "English",

volume = "33",

pages = "e1 -- 13",

journal = "Neurobiology of Aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

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Lehmann, DJ, Schuur, M, Warden, DR, Hammond, N, Belbin, O, Kölsch, H, Lehmann, MG, Wilcock, GK, Brown, K, Kehoe, PG, Morris, CM, Barker, R, Coto, E, Alvarez, V, Deloukas, P, Mateo, I, Gwilliam, R, Combarros, O, Arias-Vásquez, A, Aulchenko, YS, Ikram, MA, Breteler, MM, van Duijn, CM, Oulhaj, A, Heun, R, Cortina-Borja, M, Morgan, K, Robson, K & Smith, AD 2012, 'Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project', Neurobiology of Aging, vol. 33, no. 1, pp. e1 - 13. https://doi.org/10.1016/j.neurobiolaging.2010.07.018

TY - JOUR

T1 - Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project

AU - Lehmann, Donald J

AU - Schuur, Maaike

AU - Warden, Donald R

AU - Hammond, Naomi

AU - Belbin, Olivia

AU - Kölsch, Heike

AU - Lehmann, Michael G

AU - Wilcock, Gordon K

AU - Brown, Kristelle

AU - Kehoe, Patrick G

AU - Morris, Chris M

AU - Barker, Rachel

AU - Coto, Eliecer

AU - Alvarez, Victoria

AU - Deloukas, Panos

AU - Mateo, Ignacio

AU - Gwilliam, Rhian

AU - Combarros, Onofre

AU - Arias-Vásquez, Alejandro

AU - Aulchenko, Yurii S

AU - Ikram, M Arfan

AU - Breteler, Monique M

AU - van Duijn, Cornelia M

AU - Oulhaj, Abderrahim

AU - Heun, Reinhard

AU - Cortina-Borja, Mario

AU - Morgan, Kevin

AU - Robson, Kathryn

AU - Smith, A David

PY - 2012/1

Y1 - 2012/1

N2 - ron overload may contribute to the risk of Alzheimer's disease (AD). In the Epistasis Project, with 1757 cases of AD and 6295 controls, we studied 4 variants in 2 genes of iron metabolism: hemochromatosis (HFE) C282Y and H63D, and transferrin (TF) C2 and -2G/A. We replicated the reported interaction between HFE 282Y and TF C2 in the risk of AD: synergy factor, 1.75 (95% confidence interval, 1.1-2.8, p = 0.02) in Northern Europeans. The synergy factor was 3.1 (1.4-6.9; 0.007) in subjects with the APOEε4 allele. We found another interaction, between HFE 63HH and TF -2AA, markedly modified by age. Both interactions were found mainly or only in Northern Europeans. The interaction between HFE 282Y and TF C2 has now been replicated twice, in altogether 2313 cases of AD and 7065 controls, and has also been associated with increased iron load. We therefore suggest that iron overload may be a causative factor in the development of AD. Treatment for iron overload might thus be protective in some cases.

AB - ron overload may contribute to the risk of Alzheimer's disease (AD). In the Epistasis Project, with 1757 cases of AD and 6295 controls, we studied 4 variants in 2 genes of iron metabolism: hemochromatosis (HFE) C282Y and H63D, and transferrin (TF) C2 and -2G/A. We replicated the reported interaction between HFE 282Y and TF C2 in the risk of AD: synergy factor, 1.75 (95% confidence interval, 1.1-2.8, p = 0.02) in Northern Europeans. The synergy factor was 3.1 (1.4-6.9; 0.007) in subjects with the APOEε4 allele. We found another interaction, between HFE 63HH and TF -2AA, markedly modified by age. Both interactions were found mainly or only in Northern Europeans. The interaction between HFE 282Y and TF C2 has now been replicated twice, in altogether 2313 cases of AD and 7065 controls, and has also been associated with increased iron load. We therefore suggest that iron overload may be a causative factor in the development of AD. Treatment for iron overload might thus be protective in some cases.

U2 - 10.1016/j.neurobiolaging.2010.07.018

DO - 10.1016/j.neurobiolaging.2010.07.018

M3 - Article (Academic Journal)

C2 - 20817350

SN - 0197-4580

VL - 33

SP - e1 - 13

JO - Neurobiology of Aging

JF - Neurobiology of Aging

IS - 1

ER -

Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project

Abstract

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