Evidence map›Paper›PMID 38875006›Full record

ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2024

GWAS Identifies DPP6 as Risk Gene of Cognitive Decline in Parkinson's Disease.

Chunyu Li, Yanbing Hou, Ruwei Ou, Qianqian Wei, Lingyu Zhang, Kuncheng Liu, Junyu Lin, Xueping Chen, Wei Song, Bi Zhao and 2 more

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In one paragraph

Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Chunyu LiLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Yanbing HouLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Ruwei OuLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Qianqian WeiLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Lingyu ZhangLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Kuncheng LiuLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Junyu LinLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Xueping ChenLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Wei SongLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Bi ZhaoLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Ying WuLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Huifang ShangLaboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.ORCID 0000-0003-0947-1151

Funding

National Key Research and Development Program of China 2021YFC2501200Sichuan Science and Technology 2022ZDZX0023
6 · The paper itself

Abstract

backgroundCognitive decline is among the most common non-motor symptoms in Parkinson's disease (PD), while its physiological mechanisms remain poorly understood. Genetic factors constituted a fundamental determinant in the heterogeneity of cognitive decline among PD patients. However, the underlying genetic background was still less studied.

methodsTo explore the genetic determinants contributing to cognitive decline in PD, we performed genome-wide survival analysis using a Cox proportional hazards model in a longitudinal cohort of 450 Chinese patients with PD, and further explored the functional effect of the target variant. Additionally, we built a clinical-genetic model by incorporating clinical characteristics and polygenic risk score (PRS) to predict cognitive decline in PD.

resultsThe cohort was followed up for an average of 5.25 (SE = 2.46) years, with 95 incidents of cognitive impairment. We identified significant association between locus rs75819919 (DPP6) and accelerated cognitive decline (p = 8.63E-09, beta = 1.74, SE = 0.30). Dual-luciferase reporter assay suggested this locus might be involved in the regulation of DPP6 expression. Using data set from the UK Biobank, we identified rs75819919 was associated with cognitive performance in the general population. Incorporation of PRS increased the model's predictability, achieving an average AUC of 75.6% through fivefold cross-validation in 1 000 iterations.

conclusionsThese findings improve the current understanding of the genetic etiology of cognitive impairment in PD, and provide a novel target DPP6 to explore therapeutic options. Our results also demonstrate the potential to develop clinical-genetic model to identify patients susceptible to cognitive impairment and thus provide personalized clinical guidance.

Indexed as

Cognitive DysfunctionDipeptidyl-Peptidases and Tripeptidyl-PeptidasesGenome-Wide Association StudyParkinson DiseaseAgedChinaFemaleGenetic Predisposition to DiseaseHumansLongitudinal StudiesMaleMiddle AgedNerve Tissue ProteinsPolymorphism, Single NucleotidePotassium ChannelsProportional Hazards ModelsDipeptidyl-Peptidases and Tripeptidyl-PeptidasesDPP6 protein, humanNerve Tissue ProteinsPotassium ChannelsCognitive declineDPP6Genetic modifiersParkinson’s diseaseProgression

Identifiers

PMID38875006
PMCPMC11272050

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.