Discovering genetic mechanisms underlying the co-occurrence of Parkinson’s disease and non-motor traits

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作者
Sreemol Gokuladhas
Tayaza Fadason
Sophie Farrow
Antony Cooper
Justin M. O’Sullivan
机构
[1] University of Auckland,The Liggins Institute
[2] Maurice Wilkins Centre for Molecular Biodiscovery,St Vincent’s Clinical School
[3] UNSW Sydney,Australian Parkinson’s Mission
[4] Garvan Institute of Medical Research,MRC Lifecourse Epidemiology Unit
[5] University of Southampton,Singapore Institute for Clinical Sciences
[6] Agency for Science,undefined
[7] Technology and Research (A*STAR),undefined
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npj Parkinson's Disease | / 10卷
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摘要
Understanding the biological mechanisms that underlie the non-motor symptoms of Parkinson’s disease (PD) requires comprehensive frameworks that unravel the complex interplay of genetic risk factors. Here, we used a disease-agnostic brain cortex gene regulatory network integrated with Mendelian Randomization analyses that identified 19 genes whose changes in expression were causally linked to PD. We further used the network to identify genes that are regulated by PD-associated genome-wide association study (GWAS) SNPs. Extended protein interaction networks derived from PD-risk genes and PD-associated SNPs identified convergent impacts on biological pathways and phenotypes, connecting PD with established co-occurring traits, including non-motor symptoms. These findings hold promise for therapeutic development. In conclusion, while distinct sets of genes likely influence PD risk and outcomes, the existence of genes in common and intersecting pathways associated with other traits suggests that they may contribute to both increased PD risk and symptom heterogeneity observed in people with Parkinson’s.
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