Study explores impact of genetic risk variants on overall disease burden and healthy life years

In a recent study published in natural medicineresearchers explored genetic risk factors associated with various diseases to understand their impact on healthy life years.

The researchers estimated this impact using disability-adjusted life years (DALYs), years of healthy life lost due to a deterioration in quality of life or premature death caused by disease. .

Study: Genetic risk factors have a substantial impact on healthy life years. Image Credit: Billion Photos/Shutterstock


Studies investigating the association of genetic variants with disease risk have identified generalized pleiotropy, when one genetic variation influences two or more unrelated traits. Quantification of the impact of genetic risk factors on human health has either been limited to single disease studies or lacked comparable measures other than lifespan.

Comparative risk assessments have examined the effect of modifiable exposures like sodium intake on overall health, but a systematic assessment of the impact of genetic risk factors is still lacking. A comprehensive assessment of the influence of genetic risk factors on the overall burden of disease would be very informative for the implementation of genetic screening and live gene editing in the delivery of targeted therapy to improve quality of life.

About the study

The current study used data from two biobank studies, FinnGen and UK Biobank, and compiled genetic information from 735,748 individuals across 80 diseases. This was correlated with DALY estimates from a 2019 Global Burden of Disease (GBD) study, which estimated the DALY assigned to an extensive list of diseases and injuries for each country. Years Lived with Disability (YLD), which indicates reduced quality of life, and Years of Life Lost (YLL), indicating premature death from disease or injury, are combined to calculate DALYs.

To develop a standard for comparative risk assessment, researchers ranked genetic risk factors according to their health impacts and associated them with modifiable risk factors. This approach provides a consistent measure to compare the health impacts of genetic risk variants across various diseases.


The results indicated that at the individual level, rare genetic variants had a greater impact on DALYs than common variants. Rare deleterious genetic variants linked to cancers of the breast, ovary, prostate, liver, colon and rectum, as well as those of cardiomyopathy, myocarditis and ischemic heart disease, have the greatest impact on DALYs individual.

At the population level, these rare variants had a significantly lower impact on DALYs than the common variant due to their low frequency in a population. A variant of lipoprotein A (PLA) locus had the highest number of DALYs at the individual level and is implicated in ischemic heart disease and non-rheumatic valvular heart disease.

Common genetic variants that had a large impact on DALYs were for the risk of ischemic heart disease, dementia, prostate cancer, or type 2 diabetes. Since the number of DALYs for a disease is based on its prevalence , its contribution to premature death and its role in decreasing the quality of life, common diseases have a higher population DALY because they lead to prolonged life with disability or lead to premature death. mortality.

The authors also considered variants that affected intermediate risk factors, such as blood pressure and body mass index, when calculating DALYs. However, the variants with the high DALY scores were directly correlated with the disease and not with the intermediate risk factors.

An exception was the variant in the CHRNA5/A3/B4 group of genes, which causes nicotine addiction. Although an intermediate risk factor, this variant has resulted in high DALY scores due to its role in lung cancer, intestinal vascular disorders, aortic aneurysm, and chronic obstructive pulmonary disease.

Traits that contribute to PGS can be either cardiometabolic like coronary heart disease or type 2 diabetes, or related to pain and addiction, which include substance dependence, low back pain, chronic multisite pain, depressive disorders adults and smoking. The study found that being in the top 10% of PGS for multisite chronic pain had a large impact on DALYs.


Overall, the results indicate that genetic risk factors can have a large impact on the number of healthy years lost due to reduced quality of life or premature death from disease. The study found that some common genetic variants associated with the disease have DALYs comparable to established modifiable risk factors such as sodium intake.

Stratification of genetic risk factors according to health impacts can help prioritize treatments and interventions and reduce the impact of disease on quality of life. The authors also believe that although genetic risk factors are currently not modifiable, this information can be used to improve genetic screening and prioritize targets for live gene modification.

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