Research Paper Volume 14, Issue 16 pp 6415—6426
Heritability of R2* iron in the basal ganglia and cortex
- 1 Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Styria, Austria
- 2 Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Styria, Austria
- 3 Department of Neurology, Medical University of Graz, Styria, Austria
- 4 Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, TX 78229, USA
- 5 Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA
- 6 Research Unit-Genetic Epidemiology, Gottfried Schatz Research Centre for Cell Signalling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Styria, Austria
Received: March 31, 2022 Accepted: July 12, 2022 Published: August 9, 2022
https://doi.org/10.18632/aging.204212How to Cite
Copyright: © 2022 Hofer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: While iron is essential for normal brain functioning, elevated concentrations are commonly found in neurodegenerative diseases and are associated with impaired cognition and neurological deficits. Currently, only little is known about genetic and environmental factors that influence brain iron concentrations.
Methods: Heritability and bivariate heritability of regional brain iron concentrations, assessed by R2* relaxometry at 3 Tesla MRI, were estimated with variance components models in 130 middle-aged to elderly participants of the Austrian Stroke Prevention Family Study.
Results: Heritability of R2* iron ranged from 0.46 to 0.82 in basal ganglia and from 0.65 to 0.76 in cortical lobes. Age and BMI explained up to 12% and 9% of the variance of R2* iron, while APOE ε4 carrier status, hypertension, diabetes, hypercholesterolemia, sex and smoking explained 5% or less. The genetic correlation of R2* iron among basal ganglionic nuclei and among cortical lobes ranged from 0.78 to 0.87 and from 0.65 to 0.97, respectively. R2* rates in basal ganglia and cortex were not genetically correlated.
Conclusions: Regional brain iron concentrations are mainly driven by genetic factors while environmental factors contribute to a certain extent. Brain iron levels in the basal ganglia and cortex are controlled by distinct sets of genes.
Abbreviations
PD: Parkinson’s disease; AD: Alzheimer’s disease; HFE: hemochromatosis gene; TF: transferrin gene; APOE: Apolipoprotein E; BMI: body mass index; h2: heritability; MRI: magnetic resonance imaging; ASPS-Fam: Austrian Stroke Prevention Family Study; IQR: interquartile range; rg: genetic correlation coefficient; SNP: single nucleotide polymorphism; SOLAR: Sequential Oligogenetic Linkage Analysis Routines software; ASPS: Austrian Stroke Prevention Study; MPRAGE: magnetization prepared raid gradient echo; Vp: phenotypic variance; Vg: polygenic variance; Ve: environmental variance; FDR: false discovery rate.