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TransferGWAS of T1-weighted brain MRI data from UK Biobank. | LitMetric

AI Article Synopsis

Article Abstract

Genome-wide association studies (GWAS) traditionally analyze single traits, e.g., disease diagnoses or biomarkers. Nowadays, large-scale cohorts such as UK Biobank (UKB) collect imaging data with sample sizes large enough to perform genetic association testing. Typical approaches to GWAS on high-dimensional modalities extract predefined features from the data, e.g., volumes of regions of interest. This limits the scope of such studies to predefined traits and can ignore novel patterns present in the data. TransferGWAS employs deep neural networks (DNNs) to extract low-dimensional representations of imaging data for GWAS, eliminating the need for predefined biomarkers. Here, we apply transferGWAS on brain MRI data from UKB. We encoded 36, 311 T1-weighted brain magnetic resonance imaging (MRI) scans using DNN models trained on MRI scans from the Alzheimer's Disease Neuroimaging Initiative, and on natural images from the ImageNet dataset, and performed a multivariate GWAS on the resulting features. We identified 289 independent loci, associated among others with bone density, brain, or cardiovascular traits, and 11 regions having no previously reported associations. We fitted polygenic scores (PGS) of the deep features, which improved predictions of bone mineral density and several other traits in a multi-PGS setting, and computed genetic correlations with selected phenotypes, which pointed to novel links between diffusion MRI traits and type 2 diabetes. Overall, our findings provided evidence that features learned with DNN models can uncover additional heritable variability in the human brain beyond the predefined measures, and link them to a range of non-brain phenotypes.

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http://dx.doi.org/10.1371/journal.pgen.1011332DOI Listing

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