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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. [ABSTRACT FROM AUTHOR]

Imaging genetics is a method used to detect associations between imaging and genetic variables. Some researchers have used sparse canonical correlation analysis (SCCA) for imaging genetics. This study was conducted to improve the efficiency and interpretability of SCCA. We propose a connectivity-based penalty for incorporating biological prior information. Our proposed approach, named joint connectivity-based SCCA (JCB-SCCA), includes the proposed penalty and can handle multi-modal neuroimaging datasets. Different neuroimaging techniques provide distinct information on the brain and have been used to investigate various neurological disorders, including Parkinson’s disease (PD). We applied our algorithm to simulated and real imaging genetics datasets for performance evaluation. Our algorithm was able to select important features in a more robust manner compared with other multivariate methods. The algorithm revealed promising features of single-nucleotide polymorphisms and brain regions related to PD by using a real imaging genetic dataset. The proposed imaging genetics model can be used to improve clinical diagnosis in the form of novel potential biomarkers. We hope to apply our algorithm to cohorts such as Alzheimer’s patients or healthy subjects to determine the generalizability of our algorithm. [ABSTRACT FROM AUTHOR]

Depression is one of the most common and important neuropsychiatric symptoms in Parkinson’s disease and often becomes worse as Parkinson’s disease progresses. However, the underlying mechanisms of depression in Parkinson’s disease are not clear. The aim of our study was to find genetic features related to depression in Parkinson’s disease using an imaging genetics approach and to construct an analytical model for predicting the degree of depression in Parkinson’s disease. The neuroimaging and genotyping data were obtained from an openly accessible database. We computed imaging features through connectivity analysis derived from tractography of diffusion tensor imaging. The imaging features were used as intermediate phenotypes to identify genetic variants according to the imaging genetics approach. We then constructed a linear regression model using the genetic features from imaging genetics approach to describe clinical scores indicating the degree of depression. As a comparison, we constructed other models using imaging features and genetic features based on references to demonstrate the effectiveness of our imaging genetics model. The models were trained and tested in a five-fold cross-validation. The imaging genetics approach identified several brain regions and genes known to be involved in depression, with the potential to be used as meaningful biomarkers. Our proposed model using imaging genetic features predicted and explained the degree of depression in Parkinson’s disease appropriately (adjusted R2 larger than 0.6 over five training folds) and with a lower error and higher correlation than with other models over five test folds. [ABSTRACT FROM AUTHOR]

• A new canonical correlation analysis model, which incorporates the biologically meaningful structures with the multi-task learning framework, is proposed to discover sparse, discriminative, and interpretable shared representation across multi-modal imaging genetics data. • An efficient iteratively reweighted algorithm via alternating optimization is proposed to solve the proposed problem with proven convergence. • Extensive experiments on both simulation and real data demonstrate the promise and clinical benefits of the proposed model over multiple competing algorithms. [Display omitted] The advances in technologies for acquiring brain imaging and high-throughput genetic data allow the researcher to access a large amount of multi-modal data. Although the sparse canonical correlation analysis is a powerful bi-multivariate association analysis technique for feature selection, we are still facing major challenges in integrating multi-modal imaging genetic data and yielding biologically meaningful interpretation of imaging genetic findings. In this study, we propose a novel multi-task learning based structured sparse canonical correlation analysis (MTS2CCA) to deliver interpretable results and improve integration in imaging genetics studies. We perform comparative studies with state-of-the-art competing methods on both simulation and real imaging genetic data. On the simulation data, our proposed model has achieved the best performance in terms of canonical correlation coefficients, estimation accuracy, and feature selection accuracy. On the real imaging genetic data, our proposed model has revealed promising features of single-nucleotide polymorphisms and brain regions related to sleep. The identified features can be used to improve clinical score prediction using promising imaging genetic biomarkers. An interesting future direction is to apply our model to additional neurological or psychiatric cohorts such as patients with Alzheimer's or Parkinson's disease to demonstrate the generalizability of our method. [ABSTRACT FROM AUTHOR]