@misc{10481/82733,
year = {2023},
month = {4},
url = {https://hdl.handle.net/10481/82733},
abstract = {Neurodegeneration with brain iron accumulation (NBIA) represents a group of neurodegenerative disorders characterized by
abnormal iron accumulation in the brain. In Parkinson’s Disease (PD), iron accumulation is a cardinal feature of degenerating
regions in the brain and seems to be a key player in mechanisms that precipitate cell death. The aim of this study was to explore
the genetic and genomic connection between NBIA and PD. We screened for known and rare pathogenic mutations in autosomal
dominant and recessive genes linked to NBIA in a total of 4481 PD cases and 10,253 controls from the Accelerating Medicines
Partnership Parkinsons’ Disease Program and the UKBiobank. We examined whether a genetic burden of NBIA variants contributes
to PD risk through single-gene, gene-set, and single-variant association analyses. In addition, we assessed publicly available
expression quantitative trait loci (eQTL) data through Summary-based Mendelian Randomization and conducted transcriptomic
analyses in blood of 1886 PD cases and 1285 controls. Out of 29 previously reported NBIA screened coding variants, four were
associated with PD risk at a nominal p value < 0.05. No enrichment of heterozygous variants in NBIA-related genes risk was
identified in PD cases versus controls. Burden analyses did not reveal a cumulative effect of rare NBIA genetic variation on PD risk.
Transcriptomic analyses suggested that DCAF17 is differentially expressed in blood from PD cases and controls. Due to low
mutation occurrence in the datasets and lack of replication, our analyses suggest that NBIA and PD may be separate molecular
entities.},
organization = {National Institutes of Health (NIH)},
publisher = {Springer Nature},
title = {Exploring the genetic and genomic connection underlying neurodegeneration with brain iron accumulation and the risk for Parkinson’s disease},
doi = {10.1038/s41531-023-00496-y},
author = {Alvarez Jerez, Pilar and Ruz, Clara and Vives Montero, Francisco and Alcantud, José Luis and Reyes Ramírez, Lucía de los and Moore, Anni and Rodriguez-Losada, Noela and Saini, , Prabhjyot and Gan- Or, Ziv and Alvarado, Chelsea X. and Makarious, Mary B. and Billingsley, Kimberley J. and Blauwendraat, Cornelis and Noyce, Alastair J. and Singleton, Andrew B. and Durán, Raquel and Bandres-Ciga, Sara},
}