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

Research output: Contribution to journalArticle

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

Original languageEnglish
Pages (from-to)85-99
Number of pages15
JournalJOURNAL OF ALZHEIMERS DISEASE
Volume59
Issue number1
DOIs
StatePublished - 2017

King's Authors

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.

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