Study finds healthy lifestyle may offset genetic risk of early death

In a recent study published in the journal BMJ Evidence-based medicineresearchers used a longitudinal cohort dataset to assess how lifestyle and genetic factors are associated with longevity.

Their results show that there is an independent association between lifestyle, genetic factors and longevity, and that following a healthy lifestyle can reduce the risk of premature death and shortened lifespan due to genetic factors.

Research: Genetic predispositions, modifiable lifestyles, and their joint influence on human lifespan: Evidence from multiple cohort studies. Image credit: lusia83 / Shutterstock

background

Human longevity is known to be influenced by genetic factors, with some studies estimating heritability to be around 16%, as well as non-genetic attributes such as lifestyle.

Researchers have identified the “longevity gene” apolipoprotein E and other genetic loci that are significantly correlated with longevity.

However, even if certain people are genetically predisposed to a shorter lifespan, modifying certain lifestyle behaviors may reduce that risk. The extent to which this is offset by style is not well understood.

About research

Researchers combined cohort data from multiple sources, including the UK Biobank study, to calculate a polygenic risk score (PRS) that assesses an individual's genetic susceptibility to longevity.

Using this score, participants were categorized as long, medium, or short based on their genetically predicted human lifespan. Individuals in the lowest PRS quintile were classified as genetically predisposed to longevity.

Researchers then used PRS to determine the relationship between lifespan and certain common lifestyle indicators, such as sleep duration, body shape, physical activity, diet, alcohol intake, and smoking, as well as the relationship between lifestyle and genetics. We investigated how factors interact to influence longevity.

These lifestyle indicators were used to construct a Healthy Lifestyle Score (HLS). Based on the HLS, participants were classified as having an unfavorable lifestyle, a moderate lifestyle, and a favorable lifestyle.

The researchers calculated lifespan as the date of death minus the date of birth or the sum of ages at baseline and follow-up. Deaths due to COVID-19, injuries, and accidents were excluded. Covariates in the analysis included gender, age, comorbidities, socio-economic status, and education, collected through a baseline questionnaire.

The dataset was analyzed using a multivariable logistics regression model and a Cox proportional hazards regression model. These were adjusted for covariates and principal components of ancestry.

A flexible parametric survival model was used to calculate life expectancy for participants with different lifestyle and genetic risk classes. A multiplicative interaction model was performed to examine the interaction between lifestyle factors and PRS. Multiple sensitivity tests were conducted to assess the robustness of the results.

Investigation result

The study analyzed data from 353,742 European participants, excluding those without genetic data, those who failed quality control, and those who died from certain causes.

Median follow-up was 12.9 years, during which 24,239 people died. A PRS based on 19 independent single nucleotide polymorphisms was created and showed a linear increase in mortality risk across genetic risk categories.

Participants with high genetic risk had a 21% higher risk of death than those with low genetic risk, even after adjusting for lifestyle factors.

Additionally, HLS showed a dose-response relationship with mortality risk. People with unfavorable lifestyles had a 78% higher risk of dying than those with favorable lifestyles. This association persisted even after accounting for genetic risk.

A combined analysis of lifestyle and genetic factors found that people with high genetic risk and unfavorable lifestyles had a 104% higher risk of death compared to those with low genetic risk and favorable lifestyles. has become clear.

Conversely, people with high genetic risk but a favorable lifestyle had a 54% lower risk of death than those with an unfavorable lifestyle.

Stratified analysis was confirmatory and suggested that unfavorable lifestyle increases mortality risk for all genetic risk groups. No significant interactions were found between genetic risk and lifestyle factors. Sensitivity analyzes supported the robustness of our results.

Secondary analyzes assessed the combined effects of lifestyle and genetic risk on life expectancy.

Participants with a favorable lifestyle and low genetic risk had a significantly longer life expectancy than those with an unfavorable lifestyle and high genetic risk, with a difference in life expectancy of 6.7 years.

This study highlights the importance of lifestyle factors in extending lifespan, particularly smoking cessation, physical activity, sleep, and diet.

conclusion

This discussion highlights a review of research on the interaction of genetic and lifestyle factors on lifespan in 353,742 people.

Research shows that high genetic risk is associated with a 21% increased risk of death, and unfavorable lifestyle is associated with a 78% higher risk of death, independent of genetic factors. However, a favorable lifestyle can offset genetic predisposition by up to 62%, and certain combinations can yield better results.

Strengths include a large prospective cohort and comprehensive sensitivity analysis. Limitations include incomplete genetic understanding, short follow-up, reliance on self-reported data, and cohort representativeness.

Nevertheless, promoting healthy lifestyle behaviors may extend lifespan and reduce genetic risk, suggesting important implications for public health.