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. 2023 Feb 13;14(1):73-86.
doi: 10.1007/s13167-023-00315-7. eCollection 2023 Mar.

Integrating oculomics with genomics reveals imaging biomarkers for preventive and personalized prediction of arterial aneurysms

Yu Huang #  1   2   3 , Cong Li #  1 , Danli Shi #  4 , Huan Wang #  3 , Xianwen Shang  1   2   5 , Wei Wang  4 , Xueli Zhang  1 , Xiayin Zhang  1 , Yijun Hu  1 , Shulin Tang  1 , Shunming Liu  1 , Songyuan Luo  2 , Ke Zhao  2   6   7 , Ify R Mordi  8 , Alex S F Doney  3 , Xiaohong Yang  1 , Honghua Yu  1 , Xin Li  9 , Mingguang He  1   4   5
Affiliations

Integrating oculomics with genomics reveals imaging biomarkers for preventive and personalized prediction of arterial aneurysms

Yu Huang et al. EPMA J. .

Abstract

Objective: Arterial aneurysms are life-threatening but usually asymptomatic before requiring hospitalization. Oculomics of retinal vascular features (RVFs) extracted from retinal fundus images can reflect systemic vascular properties and therefore were hypothesized to provide valuable information on detecting the risk of aneurysms. By integrating oculomics with genomics, this study aimed to (i) identify predictive RVFs as imaging biomarkers for aneurysms and (ii) evaluate the value of these RVFs in supporting early detection of aneurysms in the context of predictive, preventive and personalized medicine (PPPM).

Methods: This study involved 51,597 UK Biobank participants who had retinal images available to extract oculomics of RVFs. Phenome-wide association analyses (PheWASs) were conducted to identify RVFs associated with the genetic risks of the main types of aneurysms, including abdominal aortic aneurysm (AAA), thoracic aneurysm (TAA), intracranial aneurysm (ICA) and Marfan syndrome (MFS). An aneurysm-RVF model was then developed to predict future aneurysms. The performance of the model was assessed in both derivation and validation cohorts and was compared with other models employing clinical risk factors. An RVF risk score was derived from our aneurysm-RVF model to identify patients with an increased risk of aneurysms.

Results: PheWAS identified a total of 32 RVFs that were significantly associated with the genetic risks of aneurysms. Of these, the number of vessels in the optic disc ('ntreeA') was associated with both AAA (β = -0.36, P = 6.75e-10) and ICA (β = -0.11, P = 5.51e-06). In addition, the mean angles between each artery branch ('curveangle_mean_a') were commonly associated with 4 MFS genes (FBN1: β = -0.10, P = 1.63e-12; COL16A1: β = -0.07, P = 3.14e-09; LOC105373592: β = -0.06, P = 1.89e-05; C8orf81/LOC441376: β = 0.07, P = 1.02e-05). The developed aneurysm-RVF model showed good discrimination ability in predicting the risks of aneurysms. In the derivation cohort, the C-index of the aneurysm-RVF model was 0.809 [95% CI: 0.780-0.838], which was similar to the clinical risk model (0.806 [0.778-0.834]) but higher than the baseline model (0.739 [0.733-0.746]). Similar performance was observed in the validation cohort, with a C-index of 0.798 (0.727-0.869) for the aneurysm-RVF model, 0.795 (0.718-0.871) for the clinical risk model and 0.719 (0.620-0.816) for the baseline model. An aneurysm risk score was derived from the aneurysm-RVF model for each study participant. The individuals in the upper tertile of the aneurysm risk score had a significantly higher risk of aneurysm compared to those in the lower tertile (hazard ratio = 17.8 [6.5-48.8], P = 1.02e-05).

Conclusion: We identified a significant association between certain RVFs and the risk of aneurysms and revealed the impressive capability of using RVFs to predict the future risk of aneurysms by a PPPM approach. Our finds have great potential to support not only the predictive diagnosis of aneurysms but also a preventive and more personalized screening plan which may benefit both patients and the healthcare system.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-023-00315-7.

Keywords: Aneurysm; Genetic risk scores; Imaging biomarker; Oculomics; Phenome-wide association analysis; Predictive preventive and personalized medicine (PPPM / 3PM); Retinal vascular features; Risk assessment.

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Conflict of interest statement

Conflict of interestThe authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Manhattan plot for the PheWAS of genetic aneurysm risks with RVFs. The x-axis represents the 91 RVFs, y-axis represent the Z-score (Z-score = β/SE) of the PheWAS findings. Different symbols represent different genetic risks of aneurysm, the blue/red colour represents whether the P value is passing the Bonferroni correction. AAA, abdominal aortic aneurysm; TAA, thoracic aortic aneurysm; ICA, intracranial aneurysm
Fig. 2
Fig. 2
RVFs associated with aneurysm GRSs, and MFS SNPs identified by PheWAS. A Forest plot demonstrating the significant RVFs that were identified by PheWAS of AAA/TAA/ICA GRSs; B Forest plot demonstrating the most common RVFs that were identified by PheWAS of MFS SNPs; C Venn diagram of the PheWAS results showing the common RVFs associated with AAA/TAA/ICA GRSs; ‘A/B/C’ reflects the corresponding blocks of RVFs shown in A; D Venn diagram of the PheWAS results showing the common RVFs associated with MFS SNPs; ‘A/B’ reflects the corresponding blocks of RVFs shown in B
Fig. 3
Fig. 3
The average C-index of the baseline, clinical risks and aneurysm-RVF model from the derivation and validation cohort. A Each coloured violin plot represents the average and distribution of C-index of different models from the derivation cohort, the C-indexes were derived from 2000 bootstrapping: B the average and distribution of C-index of different models from the validation cohort
Fig. 4
Fig. 4
Kaplan-Meier plots for aneurysm risk according to the aneurysm-RVF score. A Aneurysm-RVF score in the complete cohort; B Aneurysm-RVF score in the participants with first diagnose of the aneurysm
See this image and copyright information in PMC

References

    1. Erbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD, Eggebrecht H, Evangelista A, Falk V, Frank H, Gaemperli O, Grabenwoger M, Haverich A, Iung B, Manolis AJ, Meijboom F, Nienaber CA, Roffi M, Rousseau H, Sechtem U, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J. 35(41):2873–926. - PubMed
    1. Reimerink JJ, van der Laan MJ, Koelemay MJ, Balm R, Legemate DA. Systematic review and meta-analysis of population-based mortality from ruptured abdominal aortic aneurysm. Br J Surg. 2013;100(11):1405–1413. doi: 10.1002/bjs.9235. - DOI - PubMed
    1. Huang X, Wang Z, Shen Z, Lei F, Liu YM, Chen Z, Qin JJ, Liu H, Ji YX, Zhang P, Zhang XJ, Yang J, Cai J, She ZG, Li H. Projection of global burden and risk factors for aortic aneurysm - timely warning for greater emphasis on managing blood pressure. Ann Med. 2022;54(1):553–564. doi: 10.1080/07853890.2022.2034932. - DOI - PMC - PubMed
    1. Flores M, Glusman G, Brogaard K, Price ND, Hood L. P4 medicine: how systems medicine will transform the healthcare sector and society. Per Med. 2013;10(6):565–576. doi: 10.2217/pme.13.57. - DOI - PMC - PubMed
    1. Force USPST, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Doubeni CA, Epling JW, Jr, Kubik M, Landefeld CS, Mangione CM, Pbert L, Silverstein M, Simon MA, Tseng CW, Wong JB. Screening for abdominal aortic aneurysm: US Preventive Services Task Force recommendation statement. JAMA. 2019;322(22):2211–2218. doi: 10.1001/jama.2019.18928. - DOI - PubMed

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