Multi-organ Imaging-derived Polygenic Indexes for Brain and Body Health

Overview

Journal medRxiv

Date 2024 Jun 17

PMID 38883759

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

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