Shared Genetic Architecture between Parkinson's Disease and Brain Structural Phenotypes

Dong‐rui Ma; Sitao Li; Jing‐jing Shi; Yuan‐yuan Liang; Zheng‐wei Hu; Xiao‐yan Hao; Mingxia Li; Meng‐nan Guo; Chun‐yan Zuo; Wen‐kai Yu; Cheng‐yuan Mao; Mi‐bo Tang; Chan Zhang; Yaning Xu; Jun Wu; Shi‐lei Sun; Congcong Shi

doi:10.1002/mds.29598

journal article Nov 21, 2023

Shared Genetic Architecture between Parkinson's Disease and Brain Structural Phenotypes

Dong‐rui Ma Sitao Li Jing‐jing Shi Yuan‐yuan Liang Zheng‐wei Hu Xiao‐yan Hao Mingxia Li Meng‐nan Guo Chun‐yan Zuo Wen‐kai Yu Cheng‐yuan Mao Mi‐bo Tang Chan Zhang

Yaning Xu

Jun Wu

Shi‐lei Sun Congcong Shi

Movement Disorders Vol. 38 No. 12 pp. 2258-2268 · Wiley

View at Publisher Save 10.1002/mds.29598

Abstract

AbstractBackgroundPatients with Parkinson's disease (PD) have consistently demonstrated brain structure abnormalities, indicating the presence of shared etiological and pathological processes between PD and brain structures; however, the genetic relationship remains poorly understood.ObjectiveThe aim of this study was to investigate the extent of shared genetic architecture between PD and brain structural phenotypes (BSPs) and to identify shared genomic loci.MethodsWe used the summary statistics from genome‐wide association studies to conduct MiXeR and conditional/conjunctional false discovery rate analyses to investigate the shared genetic signatures between PD and BSPs. Subsequent expression quantitative trait loci mapping in the human brain and enrichment analyses were also performed.ResultsMiXeR analysis identified genetic overlap between PD and various BSPs, including total cortical surface area, average cortical thickness, and specific brain volumetric structures. Further analysis using conditional false discovery rate (FDR) identified 21 novel PD risk loci on associations with BSPs at conditional FDR < 0.01, and the conjunctional FDR analysis demonstrated that PD shared several genomic loci with certain BSPs at conjunctional FDR < 0.05. Among the shared loci, 16 credible mapped genes showed high expression in the brain tissues and were primarily associated with immune function–related biological processes.ConclusionsWe confirmed the polygenic overlap with mixed directions of allelic effects between PD and BSPs and identified multiple shared genomic loci and risk genes, which are likely related to immune‐related biological processes. These findings provide insight into the complex genetic architecture associated with PD. © 2023 International Parkinson and Movement Disorder Society.

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Published: Nov 21, 2023
Vol/Issue: 38(12)
Pages: 2258-2268
License: View

Authors

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Dong‐rui Ma