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1. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

   https://doi.org/10.1038/s41398-023-02341-5  

   Jain, Pritesh ; Miller-Fleming, Tyne ; Topaloudi, Apostolia ; Yu, Dongmei ; Drineas, Petros ; Georgitsi, Marianthi ; Yang, Zhiyu ; Rizzo, Renata ; Müller-Vahl, Kirsten R. ; Tumer, Zeynep ; et al ( February 2023 , Translational Psychiatry)

   Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

    

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2. A review of statistical methods in imaging genetics

   https://doi.org/10.1002/cjs.11487  

   Nathoo, Farouk S. ; Kong, Linglong ; Zhu, Hongtu ; for the Alzheimer's Disease Neuroimaging Initiative ( February 2019 , Canadian Journal of Statistics)

   With the rapid growth of modern technology, many biomedical studies are being conducted to collect massive datasets with volumes of multi‐modality imaging, genetic, neurocognitive and clinical information from increasingly large cohorts. Simultaneously extracting and integrating rich and diverse heterogeneous information in neuroimaging and/or genomics from these big datasets could transform our understanding of how genetic variants impact brain structure and function, cognitive function and brain‐related disease risk across the lifespan. Such understanding is critical for diagnosis, prevention and treatment of numerous complex brain‐related disorders (e.g., schizophrenia and Alzheimer's disease). However, the development of analytical methods for the joint analysis of both high‐dimensional imaging phenotypes and high‐dimensional genetic data, a big data squared (BD²) problem, presents major computational and theoretical challenges for existing analytical methods. Besides the high‐dimensional nature of BD², various neuroimaging measures often exhibit strong spatial smoothness and dependence and genetic markers may have a natural dependence structure arising from linkage disequilibrium. We review some recent developments of various statistical techniques for imaging genetics, including massive univariate and voxel‐wise approaches, reduced rank regression, mixture models and group sparse multi‐task regression. By doing so, we hope that this review may encourage others in the statistical community to enter into this new and exciting field of research.The Canadian Journal of Statistics47: 108–131; 2019 © 2019 Statistical Society of Canada

    

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3. Psychotic Symptom, Mood, and Cognition-associated Multimodal MRI Reveal Shared Links to the Salience Network Within the Psychosis Spectrum Disorders

   https://doi.org/10.1093/schbul/sbac158  

   Liang, Chuang ; Pearlson, Godfrey ; Bustillo, Juan ; Kochunov, Peter ; Turner, Jessica A. ; Wen, Xuyun ; Jiang, Rongtao ; Fu, Zening ; Zhang, Xiao ; Li, Kaicheng ; et al ( October 2022 , Schizophrenia Bulletin)

   Schizophrenia (SZ), schizoaffective disorder (SAD), and psychotic bipolar disorder share substantial overlap in clinical phenotypes, associated brain abnormalities and risk genes, making reliable diagnosis among the three illness challenging, especially in the absence of distinguishing biomarkers. This investigation aims to identify multimodal brain networks related to psychotic symptom, mood, and cognition through reference-guided fusion to discriminate among SZ, SAD, and BP.

   Psychotic symptom, mood, and cognition were used as references to supervise functional and structural magnetic resonance imaging (MRI) fusion to identify multimodal brain networks for SZ, SAD, and BP individually. These features were then used to assess the ability in discriminating among SZ, SAD, and BP. We observed shared links to functional and structural covariation in prefrontal, medial temporal, anterior cingulate, and insular cortices among SZ, SAD, and BP, although they were linked with different clinical domains. The salience (SAN), default mode (DMN), and fronto-limbic (FLN) networks were the three identified multimodal MRI features within the psychosis spectrum disorders from psychotic symptom, mood, and cognition associations. In addition, using these networks, we can classify patients and controls and distinguish among SZ, SAD, and BP, including their first-degree relatives. The identified multimodal SAN may be informative regarding neural mechanisms of comorbidity for psychosis spectrum disorders, along with DMN and FLN may serve as potential biomarkers in discriminating among SZ, SAD, and BP, which may help investigators better understand the underlying mechanisms of psychotic comorbidity from three different disorders via a multimodal neuroimaging perspective.

    

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4. Similarity based classification of ADHD using singular value decomposition

   https://doi.org/10.1145/3203217.3203239  

   Eslami, Taban ; Saeed, Fahad ( January 2018 , ACM International Conference on Computing Frontiers)

   Attention deficit hyperactivity disorder (ADHD) is one of the most common brain disorders among children. This disorder is considered as a big threat for public health and causes attention, focus and organizing difficulties for children and even adults. Since the cause of ADHD is not known yet, data mining algorithms are being used to help discover patterns which discriminate healthy from ADHD subjects. Numerous efforts are underway with the goal of developing classification tools for ADHD diagnosis based on functional and structural magnetic resonance imaging data of the brain. In this paper, we used Eros, which is a technique for computing similarity between two multivariate time series along with k-Nearest-Neighbor classifier, to classify healthy vs ADHD children. We designed a model selection scheme called J-Eros which is able to pick the optimum value of k for k-Nearest-Neighbor from the training data. We applied this technique to the public data provided by ADHD-200 Consortium competition and our results show that J-Eros is capable of discriminating healthy from ADHD children such that we outperformed the best results reported by ADHD-200 competition about 20 percent for two datasets. The implemented code is available as GPL license on GitHub portal of our lab at https://github.com/pcdslab/J-Eros. 

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5. Classification of Adolescent Major Depressive Disorder via Static and Dynamic Connectivity

   https://doi.org/10.1109/JBHI.2020.3043427  

   Sen, Bhaskar ; Cullen, Kathryn R. ; Parhi, Keshab K. ( December 2020 , IEEE Journal of Biomedical and Health Informatics)

   null (Ed.)

   Prior papers have explored the functional connectivity changes for patients suffering from major depressive disorder (MDD). This paper introduces an approach for classifying adolescents suffering from MDD using resting-state fMRI. Accurate diagnosis of MDD involves interviews with adolescent patients and their parents, symptom rating scales based on Diagnostic and Statistical Manual of Mental Disorders (DSM), behavioral observation as well as the experience of a clinician. Discovering predictive biomarkers for diagnosing MDD patients using functional magnetic resonance imaging (fMRI) scans can assist the clinicians in their diagnostic assessments. This paper investigates various static and dynamic connectivity measures extracted from resting-state fMRI for assisting with MDD diagnosis. First, absolute Pearson correlation matrices from 85 brain regions are computed and they are used to calculate static features for predicting MDD. A predictive sub-network extracted using sub-graph entropy classifies adolescent MDD vs. typical healthy controls with high accuracy, sensitivity and specificity. Next, approaches utilizing dynamic connectivity are employed to extract tensor based, independent component based and principal component based subject specific attributes. Finally, features from static and dynamic approaches are combined to create a feature vector for classification. A leave-one-out cross-validation method is used for the final predictor performance. Out of 49 adolescents with MDD and 33 matched healthy controls, a support vector machine (SVM) classifier using a radial basis function (RBF) kernel using differential sub-graph entropy combined with dynamic connectivity features classifies MDD vs. healthy controls with an accuracy of 0.82 for leave-one-out cross-validation. This classifier has specificity and sensitivity of 0.79 and 0.84, respectively. This performance demonstrates the utility of MRI based diagnosis of psychiatric disorders like MDD using a combination of static and dynamic functional connectivity features of the brain. 

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