Page 113 - GTM-2-3

Global Translational Medicine TEs link to Parkinson’s risk and progression

We also observed that long-distance TE polymorphism Acknowledgments
events were significantly linked to the upregulation of
several known PD risk genes, such as GBA, CAMK2D, Data used in the preparation of this article were obtained
®
®
and RPS12 (Figure 3). Functional studies have indicated from the Accelerating Medicines Partnership (AMP )
that GBA mutations disrupt the normal structure and PD (AMP PD) Knowledge Platform. For up-to-date
function of glucocerebrosidase, leading to the aggregation information on the study, visit https://www.amp-pd.org.
of alpha-synuclein and mitochondrial dysfunction, For each individual cohort, acknowledgments are listed in
ultimately exacerbating the progression of PD [65,66] . While the supplementary file.
CAMK2D and RPS12 are loci that have been confirmed Funding
to be associated with the risk of PD in GWAS studies,
there remains a lack of relevant functional studies . This study is supported by the Shenzhen Fundamental
[15]
These findings suggest that further exploration of the Research Program (JCYJ20190807161601692), National
connection between TE polymorphisms and PD-related Natural Science Foundation of China (32270701), the
genes is warranted. Fundamental Research Funds for the Central Universities,
Our study has several limitations. First, the Sun Yat-sen (22ykqb07), Young Talent Recruitment
identification of TE insertions based on short-read Project of Guangdong (2019QN01Y139), and Shenzhen
sequencing data often results in fewer detections than Key Laboratory for Systems Medicine in Inflammatory
those obtained through third-generation long-read Diseases (ZDSYS20220606100803007).
sequencing data. This leads to incomplete and less Conflict of interest
accurate coverage of TE polymorphism information
across the entire genome . Moreover, while typical All authors report no relevant financial or other conflicts of
[58]
SNP-based GWAS analyze millions of SNP genotypes interest in relation to this study.
and hundreds of thousands of samples, our TE-GWAS
study includes only around two thousand samples. As a Author contributions
result, the coverage of genome-wide variations, the power Conceptualization: Ganqiang Liu, Hao Wu
to identify associated loci, and the ability to detect rare Formal analysis: Hao Wu
variants in TE-GWAS analysis are comparatively weaker Investigation: Hao Wu
than those of classical GWAS. Third, our discoveries Methodology: Hao Wu, Junfeng Luo
of TE risk loci and the effects of TE-eQTLs were based Writing – original draft: Hao Wu
solely on individuals of European ancestry, and it is Writing – review & editing: Ganqiang Liu
essential to assess populations of diverse ancestry. Finally,
it should be noted that our TE-eQTLs analysis was Ethics approval and consent to participate
based on peripheral blood transcriptome data. Further All data utilized were authorized for download from the
investigation is required to determine whether these
associations extend to the brain or not. Accelerating Medicines Partnership in PD (AMP-PD)
databases (v2.5 release, https://amp-pd.org) on signing the
5. Conclusion AMP-PD Data Use Agreement.
Our study explored the association between TE Consent for publication
polymorphisms and the risk of PD, highlighting the
necessity of incorporating other complex genomic Not applicable.
variations in GWAS. In addition, we integrated omics Availability of data
data to explore the potential associations between TE
polymorphisms and gene expression, including risk genes The WGS, RNA-seq, genotypes, and clinical data used
related to PD. While it is challenging to fully elucidate in this study were downloaded from the AMP-PD
and establish causative links between TE polymorphisms database (https://amp-pd.org/). AMP-PD database was
and the onset and progression of PD based on current collaboratively established by the National Institutes of
evidence and data sources, we propose that the advent of Health (NIH), multiple biopharmaceutical and life science
multi-omics big data and platforms for PD research, such companies, and other organizations. The AMP-PD database
as the Global Parkinson’s Genetics Program (GP2) , will aims to identify and validate diagnostic, prognostic,
[67]
provide additional insights into the connections between and progression biomarkers for Parkinson’s disease by
TE polymorphisms and PD. This could pave the way from conducting in-depth molecular characterization and
genetics to translational medicine for PD. longitudinal clinical analysis of patient samples.

Volume 2 Issue 3 (2023) 9 https://doi.org/10.36922/gtm.1583