The endocytic membrane trafficking pathway plays a major role in the risk of Parkinson's disease

Movement Disorders : Official Journal of the Movement Disorder Society
Sara Bandres-CigaAndrew B Singleton

Abstract

PD is a complex polygenic disorder. In recent years, several genes from the endocytic membrane-trafficking pathway have been suggested to contribute to disease etiology. However, a systematic analysis of pathway-specific genetic risk factors is yet to be performed. To comprehensively study the role of the endocytic membrane-trafficking pathway in the risk of PD. Linkage disequilibrium score regression was used to estimate PD heritability explained by 252 genes involved in the endocytic membrane-trafficking pathway including genome-wide association studies data from 18,869 cases and 22,452 controls. We used pathway-specific single-nucleotide polymorphisms to construct a polygenic risk score reflecting the cumulative risk of common variants. To prioritize genes for follow-up functional studies, summary-data based Mendelian randomization analyses were applied to explore possible functional genomic associations with expression or methylation quantitative trait loci. The heritability estimate attributed to endocytic membrane-trafficking pathway was 3.58% (standard error = 1.17). Excluding previously nominated PD endocytic membrane-trafficking pathway genes, the missing heritability was 2.21% (standard error = 0.42). Random heritabil...Continue Reading

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Feb 28, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Matthew J Farrer, Jordan Follett
Dec 10, 2019·Journal of Parkinson's Disease·International Parkinson Disease Genomics Consortium (IPDGC)
Sep 5, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Yvette C WongLaura A Volpicelli-Daley
Sep 22, 2020·Brain Communications·Catherine S StormNicholas W Wood
Mar 8, 2020·Molecular Neurodegeneration·Baraa A Hijaz, Laura A Volpicelli-Daley
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Jan 14, 2021·Scientific Reports·Margrete LangmyhrMathias Toft
Jan 30, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Amica C Müller-NedebockSoraya Bardien
Jan 29, 2020·Neurobiology of Disease·Sara Bandres-CigaAndrew B Singleton
Jan 18, 2021·The Journal of Biological Chemistry·Stephanie J GuineyScott Ayton
May 1, 2021·Cells·Liesel GoveasJean-Marc Taymans
Apr 30, 2021·Brain Research·Amrita VermaRina Bandopadhyay

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