Персонализированная профилактика: возможности и ограничения оценки полигенного риска

Хронические неинфекционные заболевания (ХНИЗ) составляют основную долю в структуре смертности во всем мире, при этом многие из них имеют многофакторную этиологию, включающую генетические факторы. В связи с этим в рамках создания индивидуальных стратегий профилактики ХНИЗ представляется перспективным проведение генетического тестирования с оценкой полигенного риска с помощью шкал генетического риска (ШГР). В настоящем обзоре будут рассмотрены ШГР различных ХНИЗ, их особенности и возможности применения.

1. Noncommunicable diseases. Global Health Estimates: Life expectancy and leading causes of death and disability. https://www.who.int/data/gho/data/themes/topics/topic-details/GHO/ncd-mortality (22 August 2023).

2. Копылова О.В., Ершова А.И., Мешков А.Н., Драпкина О.М. Профилактика сердечно-сосудистых заболеваний на протяжении жизни. Часть 1: преконцепционный, пренатальный и грудной периоды. КВТиП. 2020;19(6):2647.

3. Lewis C, Vassos E. Polygenic risk scores: from research tools to clinical instruments. Genome Med. 2020;12(1):44. DOI:10.1186/s13073-020-00742-5.

4. Choi SW, Mak TSH, O’Reilly PF. Tutorial: a guide to performing polygenic risk score analyses. Nat Protoc. 2020;15(9):2759–2772.

5. Franzago M, Santurbano D, Vitacolonna E, Stuppia L. Genes and Diet in the Prevention of Chronic Diseases in Future Generations. Int J Mol Sci. 2020;21(7).

6. Мешков А.Н., Щербакова Н.В. Молекулярно-генетическая диагностика предрасположенности к развитию ишемической болезни сердца: современное состояние проблемы. Consilium Medicum. 2016;18:22–26.

7. Inouye M, Abraham G, Nelson CP, et al. Genomic Risk Prediction of Coronary Artery Disease in 480,000 Adults: Implications for Primary Prevention. J Am Coll Cardiol. 2018;72(16):1883–1893.

8. Khera AV, Chaffin M, Aragam KG, et al. Genomewide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018;50(9):1219–1224.

9. Khera AV, Emdin CA, Drake I, et al. Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. N Engl J Med. 2016;375(24):2349–2358.

10. Hasbani NR, Ligthart S, Brown MR, et al. American Heart Association’s Life’s Simple 7: Lifestyle Recommendations, Polygenic Risk, and Lifetime Risk of Coronary Heart Disease. Circulation. 2022;145(11):808–818.

11. Klarin D, Damrauer SM, Tsao PS, et al. Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program. Circulation. 2020;142(17):1633–1646.

12. Natarajan P, Young R, Stitziel NO, et al. Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting. Circulation. 2017;135(22):2091–2101.

13. den Hoed M, Strawbridge RJ, Almgren P, et al. GWASidentified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb. Atherosclerosis. 2015;239(2):304–310.

14. Trinder M, Francis GA, Brunham LR. Association of Monogenic vs Polygenic Hypercholesterolemia With Risk of Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2020;5(4):390–399.

15. Futema M, Taylor-Beadling A, Williams M, et al. Genetic testing for familial hypercholesterolemia-past, present, and future. J Lipid Res. 2021;62:100139.

16. Trinder M, Paquette M, Cermakova L, et al. Polygenic Contribution to Low-Density Lipoprotein Cholesterol Levels and Cardiovascular Risk in Monogenic Familial Hypercholesterolemia. Circ Genomic Precis Med. 2020;13(5):515–523.

17. Marston NA, Kamanu FK, Nordio F, et al. Predicting Benefit FromEvolocumab Therapy in Patients With Atherosclerotic Disease Using a Genetic Risk Score: Results From the FOURIER Trial. Circulation. 2020;141(8):616–623.

18. Vanhoye X, Bardel C, Rimbert A, et al. A new 165-SNP low-density lipoprotein cholesterol polygenic risk score based on next generation sequencing outperforms previously published scores in routine diagnostics of familial hypercholesterolemia. Transl Res. 2023;255:119–127.

19. Лимонова А.С., Ершова А.И., Киселева А.В. и др. Оценка полигенного риска артериальной гипертензии. Кардиоваскулярная терапия и профилактика. 2022;21(12):3464.

20. Giontella A, Sjögren M, Lotta LA, et al. Clinical Evaluation of the Polygenetic Background of Blood Pressure in the PopulationBased Setting. Hypertension. 2020;77:169–77.

21. Vaura F, Kauko A, Suvila K, et al. Polygenic risk scores predict hypertension onset and cardiovascular risk. Hypertension. 2021:1119–27.

22. Sun X, Pan Y, Zhang R, et al. Life-Course Associations between Blood Pressure-Related Polygenic Risk Scores and Hypertension in the Bogalusa Heart Study. Genes (Basel). 2022;13(8).

23. Malik R, Chauhan G, Traylor M, et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2018;50(4):524–537.

24. Rutten-Jacobs LC, Larsson SC, Malik R, et al. Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306473 UK Biobank participants. BMJ. 2018;363:k4168.

25. Marston NA, Patel PN, Kamanu FK, et al. Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients With Cardiometabolic Disease. Circulation. 2021;143(5):470–478.

26. Khera AV, Chaffin M, Aragam KG, et al. Genomewide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018;50(9):1219–1224.

27. Yun JS, Jung SH, Shivakumar M, et al. Polygenic risk for type 2 diabetes, lifestyle, metabolic health, and cardiovascular disease: a prospective UK Biobank study. Cardiovasc Diabetol 21, 131 (2022).

28. Ge T, Irvin MR, Patki A, et al. Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populationns. Genome Med 14, 70 (2022).

29. Li JH, Szczerbinski L, Dawed AY, et al. A polygenic score for type 2 diabetes risk is associated with both the acute and sustained response to sulfonylureas. Diabetes. 2021;70:293–300.

30. Finer N. Medical consequences of obesity. Medicine. 2015;43(2):88–93.

31. Khera AV, Chaffin M, Wade KH, et al. Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood. Cell. 2019 Apr 18;177(3):587–596.e9.

32. Dashti HS, Miranda N, Cade BE, et al. Interaction of obesity polygenic score with lifestyle risk factors in an electronic health record biobank. BMC Med 20, 5 (2022).

33. Dudbridge F. Power and predictive accuracy of polygenic risk scores. PLoS Genet. 2013;9(3):e1003348.

34. Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747.

35. Igo RP, Kinzy TG, Cooke Bailey JN. Genetic Risk Scores. CurrProtoc Hum Genet. 2019;104(1):e95.

36. Martin AR, Gignoux CR, Walters RK, et al. Human Demographic History Impacts Genetic Risk Prediction across Diverse Populations. Am J Hum Genet. 2017;100(4):635.

37. Dron JS, Hegele RA. The evolution of geneticbased risk scores for lipids and cardiovascular disease. CurrOpinLipidol. 2019;30(2):71–81.

38. Wand H, Lambert SA, Tamburro C, et al. Improving reporting standards for polygenic scores in risk prediction studies. Nature. 2021;591(7849):211–219.