Dataset Information

Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease.

ABSTRACT:

Background and objectives

Evidence suggests that either family history or polygenic risk score (PRS) is associated with developing Parkinson disease (PD). However, little is known about the longitudinal prognosis of PD according to family history and higher PRS.

Methods

From the Parkinson's Progression Markers Initiative database, 395 patients with PD who followed up for more than 2 years were grouped into those with family history within first-degree, second-degree, and third-degree relatives (N = 127 [32.2%]) vs those without (N = 268 [67.8%]). The PRS of 386 patients was computed using whole-genome sequencing data. Longitudinal assessment of motor, cognition, and imaging based on dopaminergic degeneration was conducted during the regular follow-up period. Effects of family history, PRS, or both on longitudinal changes of cognition, motor severity, and nigrostriatal degeneration were tested using a linear mixed model. The risk of freezing of gait (FOG) according to family history was assessed using the Kaplan-Meier analysis and Cox regression models.

Results

During a median follow-up of 9.1 years, PD with positive family history showed a slower decline of caudate dopamine transporter uptake (β estimate of family history × time = 0.02, 95% CI = 0.002-0.036, p = 0.027). Family history of PD and higher PRS were independently associated with a slower decline of Montreal Cognitive Assessment (β estimate of family history × time = 0.12, 95% CI = 0.02-0.22, p = 0.017; β estimate of PRS × time = 0.09, 95% CI = 0.03-0.16, p = 0.006). In those 364 patients without FOG at baseline, PD with positive family history had a lower risk of FOG (hazard ratio of family history = 0.57, 95% CI = 0.38-0.84, p = 0.005).

Discussion

Having a family history of PD predicts slower progression of cognitive decline and caudate dopaminergic degeneration, and less FOG compared with those without a family history independent of PRS. Taken together, information on family history could be used as a proxy for the clinical heterogeneity of PD.

Trial registration information

The study was registered at clinicaltrials.gov (NCT01141023), and the enrollment began June 1, 2010.

SUBMITTER: Park M

PROVIDER: S-EPMC10759146 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease.

Park Mincheol M Lee Young-Gun YG

Neurology. Genetics 20231208 1

<h4>Background and objectives</h4>Evidence suggests that either family history or polygenic risk score (PRS) is associated with developing Parkinson disease (PD). However, little is known about the longitudinal prognosis of PD according to family history and higher PRS.<h4>Methods</h4>From the Parkinson's Progression Markers Initiative database, 395 patients with PD who followed up for more than 2 years were grouped into those with family history within first-degree, second-degree, and third-deg ...[more]

PMID: 38169864

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Dataset Information

Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease.

Background and objectives

Methods

Results

Discussion

Trial registration information

Publications

Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease.

Similar Datasets

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