Abstract

The age at onset (AAO) is an important determinant in Parkinson’s disease (PD). Neuroimaging genetics is suitable for studying AAO in PD as it jointly analyzes imaging and genetics. We aimed to identify features associated with AAO in PD by applying the objective-specific neuroimaging genetics approach and constructing an AAO prediction model. Our objective-specific neuroimaging genetics extended the sparse canonical correlation analysis by an additional data type related to the target task to investigate possible associations of the imaging–genetic, genetic–target, and imaging–target pairs simultaneously. The identified imaging, genetic, and combined features were used to construct analytical models to predict the AAO in a nested five-fold cross-validation. We compared our approach with those from two feature selection approaches where only associations of imaging–target and genetic–target were explored. Using only imaging features, AAO prediction was accurate in all methods. Using only genetic features, the results from other methods were worse or unstable compared to our model. Using both imaging and genetic features, our proposed model predicted the AAO well (r = 0.5486). Our findings could have significant impacts on the characterization of prodromal PD and contribute to diagnosing PD early because genetic features could be measured accurately from birth.

Highlights

  • The age at onset (AAO) is an important determinant in Parkinson’s disease (PD)

  • We extended the sparse Canonical correlation analysis (CCA) to include a third data type related to the target task (i.e., AAO of PD), which leads to simultaneously exploring the associations of the imaging–genetic, genetic–target, and imaging–target pairs

  • Neuroimaging features that can reflect the differences in the brain structure and function with respect to AAO of PD were computed from the fractional anisotropy (FA) of diffusion tensor imaging (DTI) that is a sensitive method to assess PD pathophysiology and s­ everity[13]

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Summary

Introduction

The age at onset (AAO) is an important determinant in Parkinson’s disease (PD). Neuroimaging genetics is suitable for studying AAO in PD as it jointly analyzes imaging and genetics. We aimed to identify features associated with AAO in PD by applying the objective-specific neuroimaging genetics approach and constructing an AAO prediction model. Our objective-specific neuroimaging genetics extended the sparse canonical correlation analysis by an additional data type related to the target task to investigate possible associations of the imaging–genetic, genetic–target, and imaging– target pairs simultaneously. We extended the sparse CCA to include a third data type related to the target task (i.e., AAO of PD), which leads to simultaneously exploring the associations of the imaging–genetic, genetic–target, and imaging–target pairs. We applied the objective-specific neuroimaging genetics approach to identify genetic and imaging features associated with AAO in PD patients, not in healthy controls.

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