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.

Alexander Rakowski

Remo Monti

Christoph Lippert

PLoS Genetics

PLOS GENETICS 由一个国际编辑委员会管理，该委员会由主编 GREG BARSH（哈德逊阿尔法生物技术研究所和斯坦福大学医学院）和 GREG COPENHAVER（北卡罗来纳大学教堂山分校）领导。发表的文章PLOS GENETICS 中的 IN 存档在 PUBMED CENTRAL 中并在 PUBMED 中引用。

PLOS GENETICS is managed by an international editorial board led by editors-in-chief GREG BARSH (Hudson Alpha Institute for Biotechnology and Stanford University School of Medicine) and GREG COPENHAVER (University of North Carolina at Chapel Hill). Articles published in PLOS GENETICS are archived in PUBMED CENTRAL and cited in PUBMED.

《PLoS Genetics》由国际编辑委员会管理，主编为GREG BARSH（哈德逊阿尔法生物技术研究所和斯坦福大学医学院）和GREG COPENHAVER（北卡罗来纳大学教堂山分校）。该期刊发表的文章会在PUBMED CENTRAL进行存档，并在PUBMED中引用。

Category	Quartile
生物学	2
生物学, 遗传学	2

TransferGWAS of T1-weighted brain MRI data from UK Biobank

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