Multi-organ imaging-derived polygenic indexes for brain and body health.
Xiaochen Yang, Patrick F Sullivan, Bingxuan Li, Zirui Fan, Dezheng Ding, Juan Shu, Yuxin Guo, Peristera Paschou, Jingxuan Bao, Li Shen, Marylyn D Ritchie, Gideon Nave, Michael L Platt, Tengfei Li, Hongtu Zhu, Bingxin Zhao
Author Information
Xiaochen Yang: Department of Statistics, Purdue University, West Lafayette, IN 47907, USA.
Patrick F Sullivan: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Bingxuan Li: UCLA Samueli School of Engineering, Los Angeles, CA 90095, USA.
Zirui Fan: Department of Statistics and Data Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dezheng Ding: Department of Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Juan Shu: Department of Statistics, Purdue University, West Lafayette, IN 47907, USA.
Yuxin Guo: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Peristera Paschou: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Jingxuan Bao: Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Li Shen: Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Marylyn D Ritchie: Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gideon Nave: Marketing Department, University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael L Platt: Marketing Department, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tengfei Li: Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Hongtu Zhu: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Bingxin Zhao: Department of Statistics and Data Science, University of Pennsylvania, Philadelphia, PA 19104, USA.
The UK Biobank (UKB) imaging project is a crucial resource for biomedical research, but is limited to 100,000 participants due to cost and accessibility barriers. Here we used genetic data to predict heritable imaging-derived phenotypes (IDPs) for a larger cohort. We developed and evaluated 4,375 IDP genetic scores (IGS) derived from UKB brain and body images. When applied to UKB participants who were not imaged, IGS revealed links to numerous phenotypes and stratified participants at increased risk for both brain and somatic diseases. For example, IGS identified individuals at higher risk for Alzheimer's disease and multiple sclerosis, offering additional insights beyond traditional polygenic risk scores of these diseases. When applied to independent external cohorts, IGS also stratified those at high disease risk in the All of Us Research Program and the Alzheimer's Disease Neuroimaging Initiative study. Our results demonstrate that, while the UKB imaging cohort is largely healthy and may not be the most enriched for disease risk management, it holds immense potential for stratifying the risk of various brain and body diseases in broader external genetic cohorts.
