ArticleNPJ Parkinson's disease2023
Genome-wide case-only analysis of gene-gene interactions with known Parkinson's disease risk variants reveals link between LRRK2 and SYT10.
Article in NPJ Parkinson's disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- A prototype-augmented graph representation learning framework for identifying brain disorder-associated genes and facilitating drug repurposing.PLoS computational biology · 2026Article
- Characterisation of the function of a lncRNA containing SINE-VNTR-Alu 67 to regulate the genes at theExperimental biology and medicine (Maywood, N.J.) · 2025Article
- Scrutinizing neurodegenerative diseases: decoding the complex genetic architectures through a multi-omics lens.Human genomics · 2024Review
- Micro-and mesoscale aspects of neurodegeneration in engineered human neural networks carrying the LRRK2 G2019S mutation.Frontiers in cellular neuroscience · 2024Article
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Authors and funding
25 authors.
Funding
Abstract
The effects of one genetic factor upon Parkinson's disease (PD) risk may be modified by other genetic factors. Such gene-gene interaction (G×G) could explain some of the 'missing heritability' of PD and the reduced penetrance of known PD risk variants. Using the largest single nucleotide polymorphism (SNP) genotype data set currently available for PD (18,688 patients), provided by the International Parkinson's Disease Genomics Consortium, we studied G×G with a case-only (CO) design. To this end, we paired each of 90 SNPs previously reported to be associated with PD with one of 7.8 million quality-controlled SNPs from a genome-wide panel. Support of any putative G×G interactions found was sought by the analysis of independent genotype-phenotype and experimental data. A total of 116 significant pairwise SNP genotype associations were identified in PD cases, pointing towards G×G. The most prominent associations involved a region on chromosome 12q containing SNP rs76904798, which is a non-coding variant of the LRRK2 gene. It yielded the lowest interaction p-value overall with SNP rs1007709 in the promoter region of the SYT10 gene (interaction OR = 1.80, 95% CI: 1.65-1.95, p = 2.7 × 10
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Registered trials
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