hypertension and diabetes) and lifestyle behaviours, Figure 5: Summary of major risk factors for cardiovascular disease, Adapted from Health Hub: Healthy Living www.healthhub.sg/live-healthy/16/screening_heart_disease, Men and women are dierently susceptible to certain types of CVD. I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. It is important to note that these hypotheses about polygenic scores based on the BCW framework are, speculative and have not yet been tested in empirical research studies. Circulation. statins and/or are not making lifestyle behavioural changes. 2015 Aug; 33: 10-6. models for stratied disease prevention. Circulation. Population-wide health promotion includes e, smoking (e.g. Exclusion of other major risk factors has suggested an independent role for, SES in CVD risk, showing that measures of SES capture inuencing forces in ways that other major risk, factors do not. Usher-Smith JA, Silarova B, Schuit E, estimates to healthcare professionals and patients: a systema, prevention of cardiovascular disease: a systematic review, 146. 112. It is seen as a preventative programme rather than a scr, . variant...or not? A number of SNP arrays are commercially available. More, generally, poor cardiovascular health can also lead to chr, and the onset of vascular dementia. Early studies examined the behavioural impact of standalone polygenic scores for common, has subsequently been reported in several inuential systematic reviews and widely cited. We also estimated the impact of the founder French-Canadian familial hypercholesterolemia deletion ( LDLR delta > 15kb deletion) on CAD risk in one of these cohorts and used this estimate to calibrate the impact of the PRS. 2016 388(10043): 530-2. uk/government/publications/health-matters-combating-high-blood-pressure/health-matters-. For example, would targeting lower LDL thresholds in people with high polygenic scores reduce their risk of CAD? up of patients with type 2 diabetes living in Scotland. cardiovascular disease: systematic review, on reducing cardiovascular risk: A pilot randomized controlled study, for substantial improvement. In contrast, PRS gave the highest OR for incident stage 2+ cancers, [IQR-OR 1.79 (95% CI 1.30–2.46)]. the biological impact of these variants, which is often deleterious and sucient by itself for disease, manifestation. Even in r, number of SNPs is usually obtained using GW. Here, we develop and validate genome-wide polygenic scores for five common diseases. The main challenge in developing a polygenic score is in determining which SNPs t, disease-associated weighting to assign to these. On-going research, to determine the public acceptability of programmes with a focus on prevention (as opposed t, detection) are also needed, together with research and evaluation to determine potential wider societal, Thorough assessment of the application of polygenic scores for car, that this is a promising area of development; a polygenic score f, hence potentially support more eective prevention. We calculated both PRS (GPSCAD and metaGRSCAD) in French-Canadian individuals from three cohorts totaling 3639 prevalent CAD cases and 7382 controls, and tested their power to predict prevalent, incident and recurrent CAD. Potential, downstream benets of this improved risk assessment include more eective allocation of r, to those who are most likely to benet, hopefully leading to reduction/delay in onset of illness. Model selection will most likely be inuenced by practical, considerations and trade-os between obtaining genotype data, processes for score construction and, Examination of the literature has shown that the trend in this eld is towar, number of SNPs in score construction. Other studies have explored the psychological and behavioural eects of providing patients with, results from genetic testing for high penetrance variants that conf, studies of PRS, due to the nature of the information (e.g. applied to assessing risk for common diseases using genetic information: number of known high-penetrant variants that hav, Genetic test evaluation frameworks have largely been used in the context of tests developed f, Mendelian diseases, or hereditary forms of common diseases, mean that in this context genetic testing, is usually diagnostic or very highly predictive, as the assumption is that the presence of the variant. These include communication and system lev, to help address social determinants of health in order to increase medication adherence and motiv, Although clinical utility may not immediately be derived from PRS through motivating risk-reducing, behaviours, it is likely to be through improved accur, motivating risk-reducing action among individuals who would not have been identied as high-risk, outweighed by the benets, this suggests that PRS as part of a CVD risk assessment may have clinical. genetic testing of variants for heritable disorders. Cir. disease, and death: systematic review and meta-analysis. change. Importantly AUC provides information of the discriminative capacity and does not summarise the, clinical impact of the model, as there is no set threshold for AUC that can be consider, The optimal AUC is dependent on the intended use of the model. what-we-do/Into-practice/measuring-uptake/nice-impac. Individual, genetic information could provide the earliest indication of a predisposition to such build-up, preventative action to be taken in high-risk individuals from a younger age, perhaps even bef, Interventions in these high-risk individuals could be close monitoring, lifestyle adaptation or use of, therapeutics. approaches, both systematic and opportunistic, Cardiovascular disease (CVD) prevention prog. More detailed assessment of risk can inform decisions about individual level health promotion and, drug treatments, which are usually oered to those individuals c, This is because these individuals have the potential to gain the most from interventions. nd a model that generalises to an external validation dataset. Eur Heart J. Individual genetic information could, provide the earliest indication of a predisposition to such build-up, allowing pr, be taken in high-risk individuals from a younger age, perhaps even before plaques begin building in, childhood. association data for all the variants analysed across the genome in a given study, Given that common diseases could be inuenced by many SNP, developed to examine the impact of multiple SNPs on disease risk. evidence to suggest that incorporating genetic risk information has any additional benecial impact, on individual behaviours beyond that arising from conventional risk factor information, ther, evidence of additional harm. Estimate the 10-year risk of CVD in women and men (CHD, str, lipoprotein, cholesterol ratio), smoking, family history of coronary heart disease in a rst degree, relative aged less than 60 years, type 1 and 2 diabetes, treated h, atrial brillation (AF), chronic kidney disease (stage 4 or 5), (standard deviation of repeated measures), migraine, corticosteroids, (SLE), atypical antipsychotics, severe mental illness, erectile dysfunction, lipids for the primary and secondary prevention of cardiovascular disease, England (PHE) NHS Health Check: best practice guidance, https://www.framinghamheartstudy.org/fhs-about/.