Common and rare variants in HFE are not associated with Parkinson's disease in Europeans

Neurobiol Aging. 2021 Nov:107:174-177. doi: 10.1016/j.neurobiolaging.2021.05.019. Epub 2021 Jun 8.

Abstract

A recent study suggested that the p.H63D variant in HFE, a gene involved in iron homeostasis, may modify α-synuclein pathology, the pathological hallmark of Parkinson's disease (PD). If indeed this gene and specific variant are involved in PD, we expect to find differential distribution of HFE variants when comparing PD patients and controls. We analyzed genome-wide association study (GWAS) data from 14,671 PD patients and 17,667 controls and full sequencing data from additional 1647 PD patients and 1050 controls, using logistic regression models, and burden and Kernel tests. The HFE p.H63D variant was not associated with PD, nor did all the other common variants in the HFE locus. We did not find association of rare HFE variants with PD as well in all types of burden and Kernel tests. Our results do not support a role for HFE in PD risk.

Keywords: GWAS; Iron homeostasis; Parkinson's disease; Rare variants; Sequencing; hfe.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Europe
  • Female
  • Genetic Testing
  • Genetic Variation / genetics*
  • Genome-Wide Association Study / methods*
  • Hemochromatosis Protein / genetics*
  • Homeostasis / genetics
  • Humans
  • Iron / metabolism
  • Logistic Models
  • Male
  • Negative Results*
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism
  • White People / genetics
  • alpha-Synuclein / metabolism

Substances

  • HFE protein, human
  • Hemochromatosis Protein
  • alpha-Synuclein
  • Iron