The genetics underlying imaging phenotypes and correlated physiological measures

影像技术被广泛用于疾病的早期发现和诊断。尽管在临床实践中被广泛采用，但人们对医学图像中的结构信息与生理功能的关系知之甚少，这可能有助于治疗。此外，我们对成像表型如何由遗传学决定以及疾病的遗传控制和成像表型在多大程度上是共享的理解非常有限。考虑到这一点，本项目的重点是了解遗传如何控制成像表型和相关的生理指标。具体而言，将从50多万张眼底图像中获取结构信息和功能信息。确定哪些成像表型与感兴趣的疾病具有遗传相关性（即遗传共享成分），将告知共享控制途径，并将疾病亚型和成像表型与不同的生物学途径相匹配。此外，计算建模方法可用于将结构图像转换为生理相关特征。在这个项目中，我们将从英国生物银行（UK Biobank）的视网膜图像中开发结构测量和基于模型的血流（即血流动力学）估计，这是一项大型前瞻性流行病学研究，涉及50万人。该项目的另一个目标是了解这些低水平表型是否比高水平表型具有更大的遗传贡献。我们的目标是确定影响结构和血流动力学测量的基因，并解剖它们的遗传和环境变异。进一步的研究将使我们能够分析这些基因是否有医学应用，例如，可药物基因或遗传生物标志物。此外，这个项目的挑战之一是项目中的样本数量很多，因为每个样本都必须进行分析，然后与所有其他结果合并。因此，本研究的目的，除了从眼底图像及其遗传分析中获得的知识外，还在于开发一种新的方法，将不同类型的信息结合起来，达到一个目标，如早期诊断，定期修订和建立新的治疗靶点。

Imaging techniques are widely used for early detection and diagnosis of disease. Although widely adopted in clinical practice, it is only partially understood how structural information in medical images relates to physiological function, which may amenable for treatment. Furthermore, our understanding of how imaging phenotypes are determined by genetics and to what degree the genetic control of disease and the imaging phenotypes is shared is very limited. Taken this into account, this project is focused in understanding how genetics control imaging phenotypes and correlated physiological measures. Specifically, structural information and functional information will be obtained from more than 500,000 fundus images.Identifying which imaging phenotypes have genetic correlations (i.e. a genetic shared component) with the disease of interest would inform of shared control pathways and to match disease-subtypes and imaging phenotypes to different biological pathways. Furthermore, computational modelling approaches can be used to convert structural images into physiologically relevant traits. During this project we will develop both structural measurements and modelling-based estimates of blood flow (i.e. haemodynamics) in the eye from retinal images in UK Biobank, a large prospective epidemiological study of 500,000 individuals. Another objective of this project is knowing whether these low-level phenotypes have a bigger genetic contribution than high-level phenotypes. Our goal is to identify genes influencing the structural and haemodynamic measurements and dissect their genetic and environmental variation. Further studies will allow us to analyze if these genes could have a medical application, for instance, a druggable gene or a genetic biomarker.In addition, one of the challenges of this project is the high number of samples in the project because each sample must be analyzed and then merged with all the other results. So, the purpose of this study, in addition to the knowledge obtained from the fundus images and its genetic analysis, is develop a new approach that combines different types of information towards an objective, such as early diagnosis, periodical revisions and stablishing new therapeutic targets.