IU Indianapolis ScholarWorks :: Browsing by Subject "Brain imaging genetics"

Browsing by Subject "Brain imaging genetics"

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Associating Multi-modal Brain Imaging Phenotypes and Genetic Risk Factors via A Dirty Multi-task Learning Method
(IEEE, 2020) Du, Lei; Liu, Fang; Liu, Kefei; Yao, Xiaohui; Risacher, Shannon L.; Han, Junwei; Saykin, Andrew J.; Shen, Li; Radiology and Imaging Sciences, School of Medicine
Brain imaging genetics becomes more and more important in brain science, which integrates genetic variations and brain structures or functions to study the genetic basis of brain disorders. The multi-modal imaging data collected by different technologies, measuring the same brain distinctly, might carry complementary information. Unfortunately, we do not know the extent to which the phenotypic variance is shared among multiple imaging modalities, which further might trace back to the complex genetic mechanism. In this paper, we propose a novel dirty multi-task sparse canonical correlation analysis (SCCA) to study imaging genetic problems with multi-modal brain imaging quantitative traits (QTs) involved. The proposed method takes advantages of the multi-task learning and parameter decomposition. It can not only identify the shared imaging QTs and genetic loci across multiple modalities, but also identify the modality-specific imaging QTs and genetic loci, exhibiting a flexible capability of identifying complex multi-SNP-multi-QT associations. Using the state-of-the-art multi-view SCCA and multi-task SCCA, the proposed method shows better or comparable canonical correlation coefficients and canonical weights on both synthetic and real neuroimaging genetic data. In addition, the identified modality-consistent biomarkers, as well as the modality-specific biomarkers, provide meaningful and interesting information, demonstrating the dirty multi-task SCCA could be a powerful alternative method in multi-modal brain imaging genetics.
Detecting genetic associations with brain imaging phenotypes in Alzheimer’s disease via a novel structured SCCA approach
(Elsevier, 2020-04) Du, Lei; Liu, Kefei; Yao, Xiaohui; Risacher, Shannon L.; Han, Junwei; Saykin, Andrew J.; Guo, Lei; Shen, Li; Radiology and Imaging Sciences, School of Medicine
Brain imaging genetics becomes an important research topic since it can reveal complex associations between genetic factors and the structures or functions of the human brain. Sparse canonical correlation analysis (SCCA) is a popular bi-multivariate association identification method. To mine the complex genetic basis of brain imaging phenotypes, there arise many SCCA methods with a variety of norms for incorporating different structures of interest. They often use the group lasso penalty, the fused lasso or the graph/network guided fused lasso ones. However, the group lasso methods have limited capability because of the incomplete or unavailable prior knowledge in real applications. The fused lasso and graph/network guided methods are sensitive to the sign of the sample correlation which may be incorrectly estimated. In this paper, we introduce two new penalties to improve the fused lasso and the graph/network guided lasso penalties in structured sparse learning. We impose both penalties to the SCCA model and propose an optimization algorithm to solve it. The proposed SCCA method has a strong upper bound of grouping effects for both positively and negatively highly correlated variables. We show that, on both synthetic and real neuroimaging genetics data, the proposed SCCA method performs better than or equally to the conventional methods using fused lasso or graph/network guided fused lasso. In particular, the proposed method identifies higher canonical correlation coefficients and captures clearer canonical weight patterns, demonstrating its promising capability in revealing biologically meaningful imaging genetic associations.
Identifying diagnosis-specific genotype–phenotype associations via joint multitask sparse canonical correlation analysis and classification
(Oxford, 2020-07-13) Du, Lei; Liu, Fang; Liu, Kefei; Yao, Xiaohui; Risacher, Shannon L; Han, Junwei; Guo, Lei; Saykin, Andrew J; Shen, Li; Radiology and Imaging Sciences, School of Medicine
Motivation Brain imaging genetics studies the complex associations between genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). The neurodegenerative disorders usually exhibit the diversity and heterogeneity, originating from which different diagnostic groups might carry distinct imaging QTs, SNPs and their interactions. Sparse canonical correlation analysis (SCCA) is widely used to identify bi-multivariate genotype–phenotype associations. However, most existing SCCA methods are unsupervised, leading to an inability to identify diagnosis-specific genotype–phenotype associations. Results In this article, we propose a new joint multitask learning method, named MT–SCCALR, which absorbs the merits of both SCCA and logistic regression. MT–SCCALR learns genotype–phenotype associations of multiple tasks jointly, with each task focusing on identifying one diagnosis-specific genotype–phenotype pattern. Meanwhile, MT–SCCALR cannot only select relevant SNPs and imaging QTs for each diagnostic group alone, but also allows the selection of those shared by multiple diagnostic groups. We derive an efficient optimization algorithm whose convergence to a local optimum is guaranteed. Compared with two state-of-the-art methods, MT–SCCALR yields better or similar canonical correlation coefficients and classification performances. In addition, it owns much better discriminative canonical weight patterns of great interest than competitors. This demonstrates the power and capability of MTSCCAR in identifying diagnostically heterogeneous genotype–phenotype patterns, which would be helpful to understand the pathophysiology of brain disorders.
Identifying genetic markers enriched by brain imaging endophenotypes in Alzheimer's disease
(BMC, 2022-08-01) Kim, Mansu; Wu, Ruiming; Yao, Xiaohui; Saykin, Andrew J.; Moore, Jason H.; Shen, Li; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most common type of dementia. AD is characterized by a decline of cognitive function and brain atrophy, and is highly heritable with estimated heritability ranging from 60 to 80[Formula: see text]. The most straightforward and widely used strategy to identify AD genetic basis is to perform genome-wide association study (GWAS) of the case-control diagnostic status. These GWAS studies have identified over 50 AD related susceptibility loci. Recently, imaging genetics has emerged as a new field where brain imaging measures are studied as quantitative traits to detect genetic factors. Given that many imaging genetics studies did not involve the diagnostic outcome in the analysis, the identified imaging or genetic markers may not be related or specific to the disease outcome. Results: We propose a novel method to identify disease-related genetic variants enriched by imaging endophenotypes, which are the imaging traits associated with both genetic factors and disease status. Our analysis consists of three steps: (1) map the effects of a genetic variant (e.g., single nucleotide polymorphism or SNP) onto imaging traits across the brain using a linear regression model, (2) map the effects of a diagnosis phenotype onto imaging traits across the brain using a linear regression model, and (3) detect SNP-diagnosis association via correlating the SNP effects with the diagnostic effects on the brain-wide imaging traits. We demonstrate the promise of our approach by applying it to the Alzheimer's Disease Neuroimaging Initiative database. Among 54 AD related susceptibility loci reported in prior large-scale AD GWAS, our approach identifies 41 of those from a much smaller study cohort while the standard association approaches identify only two of those. Clearly, the proposed imaging endophenotype enriched approach can reveal promising AD genetic variants undetectable using the traditional method. Conclusion: We have proposed a novel method to identify AD genetic variants enriched by brain-wide imaging endophenotypes. This approach can not only boost detection power, but also reveal interesting biological pathways from genetic determinants to intermediate brain traits and to phenotypic AD outcomes.
Identifying highly heritable brain amyloid phenotypes through mining Alzheimer's imaging and sequencing biobank data
(World Scientific, 2022) Bao, Jingxuan; Wen, Zixuan; Kim, Mansu; Zhao, Xiwen; Lee, Brian N.; Jung, Sang-Hyuk; Davatzikos, Christos; Saykin, Andrew J.; Thompson, Paul M.; Kim, Dokyoon; Zhao, Yize; Shen, Li; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
Brain imaging genetics, an emerging and rapidly growing research field, studies the relationship between genetic variations and brain imaging quantitative traits (QTs) to gain new insights into the phenotypic characteristics and genetic mechanisms of the brain. Heritability is an important measurement to quantify the proportion of the observed variance in an imaging QT that is explained by genetic factors, and can often be used to prioritize brain QTs for subsequent imaging genetic association studies. Most existing studies define regional imaging QTs using predefined brain parcellation schemes such as the automated anatomical labeling (AAL) atlas. However, the power to dissect genetic underpinnings under QTs defined in such an unsupervised fashion could be negatively affected by heterogeneity within the regions in the partition. To bridge this gap, we propose a novel method to define highly heritable brain regions. Based on voxelwise heritability estimates, we extract brain regions containing spatially connected voxels with high heritability. We perform an empirical study on the amyloid imaging and whole genome sequencing data from a landmark Alzheimer’s disease biobank; and demonstrate the regions defined by our method have much higher estimated heritabilities than the regions defined by the AAL atlas. Our proposed method refines the imaging endophenotype constructions in light of their genetic dissection, and yields more powerful imaging QTs for subsequent detection of genetic risk factors along with better interpretability.
Identifying imaging genetic associations via regional morphometricity estimation
(World Scientific, 2022) Bao, Jingxuan; Wen, Zixuan; Kim, Mansu; Saykin, Andrew J.; Thompson, Paul M.; Zhao, Yize; Shen, Li; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
Brain imaging genetics is an emerging research field aiming to reveal the genetic basis of brain traits captured by imaging data. Inspired by heritability analysis, the concept of morphometricity was recently introduced to assess trait association with whole brain morphology. In this study, we extend the concept of morphometricity from its original definition at the whole brain level to a more focal level based on a region of interest (ROI). We propose a novel framework to identify the SNP-ROI association via regional morphometricity estimation of each studied single nucleotide polymorphism (SNP). We perform an empirical study on the structural MRI and genotyping data from a landmark Alzheimer’s disease (AD) biobank; and yield promising results. Our findings indicate that the AD-related SNPs have higher overall regional morphometricity estimates than the SNPs not yet related to AD. This observation suggests that the variance of AD SNPs can be explained more by regional morphometric features than non-AD SNPs, supporting the value of imaging traits as targets in studying AD genetics. Also, we identified 11 ROIs, where the AD/non-AD SNPs and significant/insignificant morphometricity estimation of the corresponding SNPs in these ROIs show strong dependency. Supplementary motor area (SMA) and dorsolateral prefrontal cortex (DPC) are enriched by these ROIs. Our results also demonstrate that using all the detailed voxel-level measures within the ROI to incorporate morphometric information outperforms using only a single average ROI measure, and thus provides improved power to detect imaging genetic associations.
Mining High-Level Imaging Genetic Associations via Clustering AD Candidate Variants with Similar Brain Association Patterns
(MDPI, 2022-08-24) Wu, Ruiming; Bao, Jingxuan; Kim, Mansu; Saykin, Andrew J.; Moore, Jason H.; Shen, Li; Radiology and Imaging Sciences, School of Medicine
Brain imaging genetics examines associations between imaging quantitative traits (QTs) and genetic factors such as single nucleotide polymorphisms (SNPs) to provide important insights into the pathogenesis of Alzheimer's disease (AD). The individual level SNP-QT signals are high dimensional and typically have small effect sizes, making them hard to be detected and replicated. To overcome this limitation, this work proposes a new approach that identifies high-level imaging genetic associations through applying multigraph clustering to the SNP-QT association maps. Given an SNP set and a brain QT set, the association between each SNP and each QT is evaluated using a linear regression model. Based on the resulting SNP-QT association map, five SNP-SNP similarity networks (or graphs) are created using five different scoring functions, respectively. Multigraph clustering is applied to these networks to identify SNP clusters with similar association patterns with all the brain QTs. After that, functional annotation is performed for each identified SNP cluster and its corresponding brain association pattern. We applied this pipeline to an AD imaging genetic study, which yielded promising results. For example, in an association study between 54 AD SNPs and 116 amyloid QTs, we identified two SNP clusters with one responsible for amyloid beta clearances and the other regulating amyloid beta formation. These high-level findings have the potential to provide valuable insights into relevant genetic pathways and brain circuits, which can help form new hypotheses for more detailed imaging and genetics studies in independent cohorts.
Multi-task learning based structured sparse canonical correlation analysis for brain imaging genetics
(Elsevier, 2022-02) Kim, Mansu; Min, Eun Jeong; Liu, Kefei; Yan, Jingwen; Saykin, Andrew J.; Moore, Jason H.; Long, Qi; Shen, Li; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and Engineering
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.
Multi-Task Sparse Canonical Correlation Analysis with Application to Multi-Modal Brain Imaging Genetics
(Institute of Electrical and Electronics Engineers, 2021) Du, Lei; Liu, Kefei; Yao, Xiaohui; Risacher, Shannon L.; Han, Junwei; Saykin, Andrew J.; Guo, Lei; Shen, Li; Radiology and Imaging Sciences, School of Medicine
Brain imaging genetics studies the genetic basis of brain structures and functionalities via integrating genotypic data such as single nucleotide polymorphisms (SNPs) and imaging quantitative traits (QTs). In this area, both multi-task learning (MTL) and sparse canonical correlation analysis (SCCA) methods are widely used since they are superior to those independent and pairwise univariate analysis. MTL methods generally incorporate a few of QTs and could not select features from multiple QTs; while SCCA methods typically employ one modality of QTs to study its association with SNPs. Both MTL and SCCA are computational expensive as the number of SNPs increases. In this paper, we propose a novel multi-task SCCA (MTSCCA) method to identify bi-multivariate associations between SNPs and multi-modal imaging QTs. MTSCCA could make use of the complementary information carried by different imaging modalities. MTSCCA enforces sparsity at the group level via the G2,1-norm, and jointly selects features across multiple tasks for SNPs and QTs via the ℓ2,1-norm. A fast optimization algorithm is proposed using the grouping information of SNPs. Compared with conventional SCCA methods, MTSCCA obtains better correlation coefficients and canonical weights patterns. In addition, MTSCCA runs very fast and easy-to-implement, indicating its potential power in genome-wide brain-wide imaging genetics.
A Novel SCCA Approach via Truncated ℓ1-norm and Truncated Group Lasso for Brain Imaging Genetics
(Oxford University Press, 2017-09-18) Du, Lei; Liu, Kefei; Zhang, Tuo; Yao, Xiaohui; Yan, Jingwen; Risacher, Shannon L; Han, Junwei; Guo, Lei; Saykin, Andrew J.; Shen, Li; Radiology and Imaging Sciences, School of Medicine
Motivation: Brain imaging genetics, which studies the linkage between genetic variations and structural or functional measures of the human brain, has become increasingly important in recent years. Discovering the bi-multivariate relationship between genetic markers such as single-nucleotide polymorphisms (SNPs) and neuroimaging quantitative traits (QTs) is one major task in imaging genetics. Sparse Canonical Correlation Analysis (SCCA) has been a popular technique in this area for its powerful capability in identifying bi-multivariate relationships coupled with feature selection. The existing SCCA methods impose either the ℓ 1 -norm or its variants to induce sparsity. The ℓ 0 -norm penalty is a perfect sparsity-inducing tool which, however, is an NP-hard problem. Results: In this paper, we propose the truncated ℓ 1 -norm penalized SCCA to improve the performance and effectiveness of the ℓ 1 -norm based SCCA methods. Besides, we propose an efficient optimization algorithms to solve this novel SCCA problem. The proposed method is an adaptive shrinkage method via tuning τ . It can avoid the time intensive parameter tuning if given a reasonable small τ . Furthermore, we extend it to the truncated group-lasso (TGL), and propose TGL-SCCA model to improve the group-lasso-based SCCA methods. The experimental results, compared with four benchmark methods, show that our SCCA methods identify better or similar correlation coefficients, and better canonical loading profiles than the competing methods. This demonstrates the effectiveness and efficiency of our methods in discovering interesting imaging genetic associations. Availability: The Matlab code and sample data are freely available at http://www.iu.edu/∼shenlab/tools/tlpscca/ .

Browsing by Subject "Brain imaging genetics"

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