Failure to detect synergy between variants in transferrin and hemochromatosis and Alzheimer's disease in large cohort

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Alzheimer's disease (AD) is the most common cause of dementia and, despite decades of effort, there is no effective treatment. In the last decade, many association studies have identified genetic markers that are associated with AD status. Two of these studies suggest that an epistatic interaction between variants rs1049296 in the transferrin (TF) gene and rs1800562 in the homeostatic iron regulator (HFE) gene, commonly known as hemochromatosis, is in genetic association with AD. TF and HFE are involved in the transport and regulation of iron in the brain, and disrupting these processes exacerbates AD pathology through increased neurodegeneration and oxidative stress. However, by using a significantly larger data set from the Alzheimer's Disease Genetics Consortium, we fail to detect an association between TF rs1049296 or HFE rs1800562 with AD risk (TF rs1049296 p = 0.38 and HFE rs1800562 p = 0.40). In addition, logistic regression with an interaction term and a synergy factor analysis both failed to detect epistasis between TF rs1049296 and HFE rs1800562 (SF = 0.94; p = 0.48) in AD cases. Each of these analyses had sufficient statistical power (power > 0.99), suggesting that previously reported associations may be the result of more complex epistatic interactions, genetic heterogeneity, or false-positive associations because of limited sample sizes.

Original languageEnglish
Pages (from-to)142.e9-142.e12
JournalNeurobiology of Aging
Volume89
DOIs
StatePublished - May 2020

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health, National Institute on Aging (USA) grant numbers R01AG042611 and RF1AG054052 . Data was supported by the ADGC. ADGC grants: ADGC U01AG032984 , NIAGADS U24AG041689 , NCRAD U24AG21886 , and NACC U01AG016976 . Acknowledgements for ADGC support can be found here: http://www.adgenetics.org/content/acknowledgements .

Funding Information:
This work was supported by the National Institutes of Health, National Institute on Aging (USA) grant numbers R01AG042611 and RF1AG054052. Data was supported by the ADGC. ADGC grants: ADGC U01AG032984, NIAGADS U24AG041689, NCRAD U24AG21886, and NACC U01AG016976. Acknowledgements for ADGC support can be found here: http://www.adgenetics.org/content/acknowledgements. Authors' contributions: EV contributed to conceptualization, methodology, formal analysis, writing?original draft, writing?review and editing, and visualization. JDGM contributed to methodology and writing?original draft. JBM contributed to writing?original draft, writing?review and editing, and supervision. Alzheimer's Disease Genetic Consortium contributed to data curation. LS contributed to methodology and formal analysis. PKC contributed to validation and data curation. SM contributed to validation and data curation. JSKK contributed to supervision and data curation.

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • Alzheimer's disease
  • Epistasis
  • Hemochromatosis
  • Homeostatic iron regulator
  • Synergy
  • Transferrin

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology

Fingerprint

Dive into the research topics of 'Failure to detect synergy between variants in transferrin and hemochromatosis and Alzheimer's disease in large cohort'. Together they form a unique fingerprint.

Cite this