No Genetic Overlap Between Circulating Iron Levels and Alzheimer's Disease.
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.
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.