Next Article in Journal
Current Imaging Evaluation of Tumor Response to Advanced Medical Treatment in Metastatic Renal-Cell Carcinoma: Clinical Implications
Previous Article in Journal
Changes in Crystal Phase, Morphology, and Flexural Strength of As-Sintered Translucent Monolithic Zirconia Ceramic Modified by Femtosecond Laser
Brief Report

Genomic Overlap between Platelet Parameters Variability and Age at Onset of Parkinson Disease

1
Department of Epidemiology and Prevention, IRCCS NEUROMED, 86077 Pozzilli, Italy
2
Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, 86100 Campobasso, Italy
3
Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Francisco Arrebola
Appl. Sci. 2021, 11(15), 6927; https://doi.org/10.3390/app11156927
Received: 1 April 2021 / Revised: 14 July 2021 / Accepted: 21 July 2021 / Published: 28 July 2021
(This article belongs to the Special Issue The Complex Link between Inflammation and Depression)
With the increasing burden of common neurodegenerative disorders and their long-hypothesized link with platelet biology, genomic approaches have been recently used to investigate the presence of a shared genetic basis between neurodegenerative risk and platelet parameters, reporting a significant though moderate genetic correlation between Parkinson Disease (PD) risk and platelet distribution width, an index of platelet size variability. Here, we investigated the genetic overlap of platelet parameters with an endophenotype of PD, age-at-onset (PD-AAO). First, we applied a Linkage Disequilibrium (LD)-score regression to the summary statistics of a large independent Genome Wide Association Study (GWAS) previously conducted, to estimate the co-heritability based on common genetic variants. Then, we analyzed multitrait single-variant associations to identify novel loci associated with both PD-AAO and mean platelet volume (MPV). Finally, we performed gene and gene-set enrichment analyses of these associations. We observed a statistically significant genetic correlation between MPV and PD-AAO (rg (SE) = −0.215 (0.082); p = 0.009). The multitrait analysis revealed eight novel variants associated with PD-AAO and 33 with MPV. The genes most significantly enriched for associations with PD-AAO included ARHGEF3 (Rho Guanine Nucleotide Exchange Factor 3), previously associated with depression, and KALRN (Kalirin RhoGEF Kinase), encoding a PINK1 interactor previously implicated in schizophrenia, Alzheimer Disease and PD itself. Interestingly, these genes were also identified in the analysis of MPV. The most significant gene-set enrichments shared between MPV and PD-AAO were observed for coagulation- and megakaryopoiesis-related pathways. These findings provide novel hints into the common genetic basis of PD endophenotypes, platelet biology and its neuropsychiatric comorbidities, paving the way for investigating common underlying mechanisms. View Full-Text
Keywords: neurodegenerative disorders; Parkinson disease; blood platelets parameters; genetic correlation; age at onset; systemic inflammation; KALRN; ARHGEF3 neurodegenerative disorders; Parkinson disease; blood platelets parameters; genetic correlation; age at onset; systemic inflammation; KALRN; ARHGEF3
Show Figures

Figure 1

MDPI and ACS Style

Tirozzi, A.; Parisi, R.; Cerletti, C.; Donati, M.B.; de Gaetano, G.; Iacoviello, L.; Gialluisi, A. Genomic Overlap between Platelet Parameters Variability and Age at Onset of Parkinson Disease. Appl. Sci. 2021, 11, 6927. https://doi.org/10.3390/app11156927

AMA Style

Tirozzi A, Parisi R, Cerletti C, Donati MB, de Gaetano G, Iacoviello L, Gialluisi A. Genomic Overlap between Platelet Parameters Variability and Age at Onset of Parkinson Disease. Applied Sciences. 2021; 11(15):6927. https://doi.org/10.3390/app11156927

Chicago/Turabian Style

Tirozzi, Alfonsina, Roberta Parisi, Chiara Cerletti, Maria B. Donati, Giovanni de Gaetano, Licia Iacoviello, and Alessandro Gialluisi. 2021. "Genomic Overlap between Platelet Parameters Variability and Age at Onset of Parkinson Disease" Applied Sciences 11, no. 15: 6927. https://doi.org/10.3390/app11156927

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop