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  Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian Randomization Study

Pichler, I., Del Greco, F., Gögele, M., Lill, C. M., Bertram, L., Do, C. B., et al. (2013). Serum Iron Levels and the Risk of Parkinson Disease: A Mendelian Randomization Study. PLoS Medicine, 10(6), e1001462-e1001462. doi:10.1371/journal.pmed.1001462.

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2013
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2013 Pichler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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 Creators:
Pichler, I., Author
Del Greco, F., Author
Gögele, M., Author
Lill, C. M.1, Author           
Bertram, L.1, Author           
Do, C. B., Author
Eriksson, N., Author
Foroud, T., Author
Myers, R. H., Author
Nalls, M., Author
Keller, M. F., Author
Benyamin, B., Author
Whitfield, J. B., Author
Pramstaller, P. P., Author
Hicks, A. A., Author
Thompson, J. R., Author
Minelli, C., Author
Consortium, PD GWAS, Author
Consor, Int Parkinsons Dis Genomics, Author
Consor, Wellcome Trust Case Control, Author
Consortium, Genetics Iron Status, Author more..
Affiliations:
1Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479655              

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Free keywords: multiple genetic-variants genome-wide association cell-surface expression hereditary hemochromatosis substantia-nigra hfe gene in-vitro mutations metaanalysis tmprss6
 Abstract: Background: Although levels of iron are known to be increased in the brains of patients with Parkinson disease (PD), epidemiological evidence on a possible effect of iron blood levels on PD risk is inconclusive, with effects reported in opposite directions. Epidemiological studies suffer from problems of confounding and reverse causation, and mendelian randomization (MR) represents an alternative approach to provide unconfounded estimates of the effects of biomarkers on disease. We performed a MR study where genes known to modify iron levels were used as instruments to estimate the effect of iron on PD risk, based on estimates of the genetic effects on both iron and PD obtained from the largest sample meta-analyzed to date. Methods and Findings: We used as instrumental variables three genetic variants influencing iron levels, HFE rs1800562, HFE rs1799945, and TMPRSS6 rs855791. Estimates of their effect on serum iron were based on a recent genomewide meta-analysis of 21,567 individuals, while estimates of their effect on PD risk were obtained through meta-analysis of genome-wide and candidate gene studies with 20,809 PD cases and 88,892 controls. Separate MR estimates of the effect of iron on PD were obtained for each variant and pooled by meta-analysis. We investigated heterogeneity across the three estimates as an indication of possible pleiotropy and found no evidence of it. The combined MR estimate showed a statistically significant protective effect of iron, with a relative risk reduction for PD of 3% (95% CI 1%-6%; p=0.001) per 10 mu g/dl increase in serum iron. Conclusions: Our study suggests that increased iron levels are causally associated with a decreased risk of developing PD. Further studies are needed to understand the pathophysiological mechanism of action of serum iron on PD risk before recommendations can be made.

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Language(s): eng - English
 Dates: 2013-06-042012-11-032013-04-242013-06-04
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1371/journal.pmed.1001462
ISSN: 1549-1676
 Degree: -

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Title: PLoS Medicine
  Other : PLoS Med.
Source Genre: Journal
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Affiliations:
Publ. Info: Public Library of Science
Pages: - Volume / Issue: 10 (6) Sequence Number: - Start / End Page: e1001462 - e1001462 Identifier: ISSN: 1549-1277
CoNE: https://pure.mpg.de/cone/journals/resource/111086125839050