No Genetic Overlap between Circulating Iron Levels and Alzheimer's Disease

Michelle K. Lupton; Beben Benyamin; Petroula Proitsi; Dale R. Nyholt; Manuel A. Ferreira; Grant W. Montgomery; Andrew C. Heath; Pamela A. Madden; Sarah E. Medland; Scott D. Gordon; Simon Lovestone; Magda Tsolaki; Iwona Kloszewska; Hilkka Soininen; Patrizia Mecocci; Bruno Vellas; John F. Powell; Ashley I. Bush; Margaret J. Wright; Nicholas G. Martin; John B. Whitfield

doi:10.3233/JAD-170027

No Genetic Overlap between Circulating Iron Levels and Alzheimer's Disease

Michelle K. Lupton, Beben Benyamin, Petroula Proitsi, Dale R. Nyholt, Manuel A. Ferreira, Grant W. Montgomery, Andrew C. Heath, Pamela A. Madden, Sarah E. Medland, Scott D. Gordon, Simon Lovestone, Magda Tsolaki, Iwona Kloszewska, Hilkka Soininen, Patrizia Mecocci, Bruno Vellas, John F. Powell, Ashley I. Bush, Margaret J. Wright, Nicholas G. MartinJohn B. Whitfield

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10 Scopus citations

Abstract

Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n∼10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n∼9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.

Original language	English
Pages (from-to)	85-99
Number of pages	15
Journal	Journal of Alzheimer's Disease
Volume	59
Issue number	1
DOIs	https://doi.org/10.3233/JAD-170027
State	Published - 2017

Keywords

Alzheimer's disease
apolipoproteins E
dementia
ferritin
genetic profile scores
genome-wide association study
iron
population genetics
transferrin

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10.3233/JAD-170027

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Lupton, M. K., Benyamin, B., Proitsi, P., Nyholt, D. R., Ferreira, M. A., Montgomery, G. W., Heath, A. C., Madden, P. A., Medland, S. E., Gordon, S. D., Lovestone, S., Tsolaki, M., Kloszewska, I., Soininen, H., Mecocci, P., Vellas, B., Powell, J. F., Bush, A. I., Wright, M. J., ... Whitfield, J. B. (2017). No Genetic Overlap between Circulating Iron Levels and Alzheimer's Disease. Journal of Alzheimer's Disease, 59(1), 85-99. https://doi.org/10.3233/JAD-170027

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title = "No Genetic Overlap between Circulating Iron Levels and Alzheimer's Disease",

abstract = "Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n∼10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n∼9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.",

keywords = "Alzheimer's disease, apolipoproteins E, dementia, ferritin, genetic profile scores, genome-wide association study, iron, population genetics, transferrin",

author = "Lupton, {Michelle K.} and Beben Benyamin and Petroula Proitsi and Nyholt, {Dale R.} and Ferreira, {Manuel A.} and Montgomery, {Grant W.} and Heath, {Andrew C.} and Madden, {Pamela A.} and Medland, {Sarah E.} and Gordon, {Scott D.} and Simon Lovestone and Magda Tsolaki and Iwona Kloszewska and Hilkka Soininen and Patrizia Mecocci and Bruno Vellas and Powell, {John F.} and Bush, {Ashley I.} and Wright, {Margaret J.} and Martin, {Nicholas G.} and Whitfield, {John B.}",

year = "2017",

doi = "10.3233/JAD-170027",

language = "English",

volume = "59",

pages = "85--99",

journal = "Journal of Alzheimer's Disease",

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Lupton, MK, Benyamin, B, Proitsi, P, Nyholt, DR, Ferreira, MA, Montgomery, GW, Heath, AC , Madden, PA, Medland, SE, Gordon, SD, Lovestone, S, Tsolaki, M, Kloszewska, I, Soininen, H, Mecocci, P, Vellas, B, Powell, JF, Bush, AI, Wright, MJ, Martin, NG & Whitfield, JB 2017, 'No Genetic Overlap between Circulating Iron Levels and Alzheimer's Disease', Journal of Alzheimer's Disease, vol. 59, no. 1, pp. 85-99. https://doi.org/10.3233/JAD-170027

TY - JOUR

T1 - No Genetic Overlap between Circulating Iron Levels and Alzheimer's Disease

AU - Lupton, Michelle K.

AU - Benyamin, Beben

AU - Proitsi, Petroula

AU - Nyholt, Dale R.

AU - Ferreira, Manuel A.

AU - Montgomery, Grant W.

AU - Heath, Andrew C.

AU - Madden, Pamela A.

AU - Medland, Sarah E.

AU - Gordon, Scott D.

AU - Lovestone, Simon

AU - Tsolaki, Magda

AU - Kloszewska, Iwona

AU - Soininen, Hilkka

AU - Mecocci, Patrizia

AU - Vellas, Bruno

AU - Powell, John F.

AU - Bush, Ashley I.

AU - Wright, Margaret J.

AU - Martin, Nicholas G.

AU - Whitfield, John B.

PY - 2017

Y1 - 2017

N2 - Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n∼10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n∼9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.

AB - Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect on AD risk? We evaluate the effects of peripheral iron on AD risk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n∼10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n∼9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.

KW - Alzheimer's disease

KW - apolipoproteins E

KW - dementia

KW - ferritin

KW - genetic profile scores

KW - genome-wide association study

KW - iron

KW - population genetics

KW - transferrin

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SN - 1387-2877

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SP - 85

EP - 99

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

IS - 1

ER -

No Genetic Overlap between Circulating Iron Levels and Alzheimer's Disease

Abstract

Keywords

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