Brain imaging genetics is an important research topic in brain science, which combines genetic variations and brain structures or functions to uncover the genetic basis of brain disorders. Imaging data collected by different technologies, measuring the same brain distinctly, might carry complementary but different information. Unfortunately, we do not know the extent to which phenotypic variance is shared among multiple imaging modalities, which might trace back to the complex genetic mechanism. In this study, we propose a novel dirty multi-task SCCA to analyze imaging genetics problems with multiple modalities of brain imaging quantitative traits (QTs) involved. The proposed method can not only identify the shared SNPs and QTs across multiple modalities, but also identify the modality-specific SNPs and QTs, showing a flexible capability of discovering the complex multi-SNP-multi-QT associations. Compared with the multi-view SCCA and multi-task SCCA, our method shows better canonical correlation coefficients and canonical weights on both synthetic and real neuroimaging genetic data. This demonstrates that the proposed dirty multi-task SCCA could be a meaningful and powerful alternative method in multi-modal brain imaging genetics.
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Identifying progressive imaging genetic patterns via multi-task sparse canonical correlation analysis: a longitudinal study of the ADNI cohort
Identifying the genetic basis of the brain structure, function and disorder by using the imaging quantitative traits (QTs) as endophenotypes is an important task in brain science. Brain QTs often change over time while the disorder progresses and thus understanding how the genetic factors play roles on the progressive brain QT changes is of great importance and meaning. Most existing imaging genetics methods only analyze the baseline neuroimaging data, and thus those longitudinal imaging data across multiple time points containing important disease progression information are omitted.
We propose a novel temporal imaging genetic model which performs the multi-task sparse canonical correlation analysis (T-MTSCCA). Our model uses longitudinal neuroimaging data to uncover that how single nucleotide polymorphisms (SNPs) play roles on affecting brain QTs over the time. Incorporating the relationship of the longitudinal imaging data and that within SNPs, T-MTSCCA could identify a trajectory of progressive imaging genetic patterns over the time. We propose an efficient algorithm to solve the problem and show its convergence. We evaluate T-MTSCCA on 408 subjects from the Alzheimer’s Disease Neuroimaging Initiative database with longitudinal magnetic resonance imaging data and genetic data available. The experimental results show that T-MTSCCA performs either better than or equally to the state-of-the-art methods. In particular, T-MTSCCA could identify higher canonical correlation coefficients and capture clearer canonical weight patterns. This suggests that T-MTSCCA identifies time-consistent and time-dependent SNPs and imaging QTs, which further help understand the genetic basis of the brain QT changes over the time during the disease progression.
The software and simulation data are publicly available at https://github.com/dulei323/TMTSCCA.
Supplementary data are available at Bioinformatics online.
- NSF-PAR ID:
- 10425974
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Bioinformatics
- Volume:
- 35
- Issue:
- 14
- ISSN:
- 1367-4803
- Page Range / eLocation ID:
- p. i474-i483
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Materials and Methods The participants, ages 65–85, included 266 healthy controls (HC), 572 volunteers with mild cognitive impairment (MCI), and 188 Alzheimer's disease (AD) patients. Genotype dosage data for AD‐associated single nucleotide polymorphisms (SNPs) were extracted from the imputed ADNI genetics archive using sample‐major additive coding. Such 29 SNPs were selected, representing a subset of independent SNPs reported to be highly associated with AD in a recent AD meta‐GWAS study by Jansen and colleagues
. Results We identified the significant correlations between the 29 genomic markers (GMs) and the 200 neuroimaging markers (NIMs). The odds ratios and relative risks for AD and MCI (relative to HC) were predicted using multinomial linear models.
Discussion In the HC and MCI cohorts, mainly cortical thickness measures were associated with GMs, whereas the AD cohort exhibited different GM‐NIM relations. Network patterns within the HC and AD groups were distinct in cortical thickness, volume, and proportion of White to Gray Matter (pct), but not in the MCI cohort. Multinomial linear models of clinical diagnosis showed precisely the specific NIMs and GMs that were most impactful in discriminating between AD and HC, and between MCI and HC.
Conclusion This study suggests that advanced analytics provide mechanisms for exploring the interrelations between morphometric indicators and GMs. The findings may facilitate further clinical investigations of phenotypic associations that support deep systematic understanding of AD pathogenesis.
