Genetics and Healthspan:
Teasing out what's actually important
Genetic studies, especially large genome-wide association studies, can be informative when looking at what is really important for healthspan. Essentially, these types of studies look to see which genetic variants are linked to outcomes — real-life people, real outcomes, and large data sets.
A 2022 study published in Nature Medicine estimated the effects of genetic variants on DALYs (disability-adjusted life years). DALYs measure ‘lost healthy life years’ — or the opposite side of healthspan.
The results showed that a common genetic variant in the LPA gene had the strongest effect on DALYs for an individual. Additionally, a combination of genetic variants that increased pain was also tied to reduced healthy years. (If you’ve done genetic testing, go to Genetic Lifehack’s LPA article to check your data — this article is free and open to everyone.)
Other genes that impacted healthy years included HLA genes, heart-related genes, and APOE (Alzheimer’s).
Among the heart-related genes, NOS3 (nitric oxide synthase) and PCSK9 (LDL cholesterol levels) were top hits.
Interestingly, a variant in the CHRNA5 gene al was also statistically significant. The variant is linked to nicotine dependence, showing that people more susceptible to nicotine dependence are statistically likelier to smoke more cigarettes and to smoke for a longer time.
Rare mutations, such as in cancer-related genes, were also considered. For example, carrying a BRCA1 mutation (breast cancer risk factor) was associated with an average loss of 4 healthy years.
The study used data from the UK Biobank (400,000+ people) and the FinnGen (300,000+ people) biobank. So it is important to note that the participants were skewed toward European Caucasian background.[ref]
What did previous genetics studies show?
A previous study looked at healthspan and genetics, with some overlapping genes. The study cohort was from the UK, using the UK Biobank information on genetics combined with health records.[ref]
The top reasons for the end of healthspan are cancer, diabetes, and heart attacks. While cancer topped the list for ending healthspan, the study found that genetics wasn’t a significant player (except for cigarette smoking). Instead, genetic variants related to heart disease (heart attack, chronic heart failure), stroke, and diabetes were the stronger hits for healthspan.
Surprisingly, this study did not find a link between healthspan and APOE genetic variants related to Alzheimer’s disease.
Once again, the most significant impact factor found was in the LPA gene, which encodes lipoprotein (a). Lp(a) levels are highly genetic — and a big risk factor for heart attacks.
Another large impact on healthspan was found in the TCF7L2 gene, which is highly associated with an increased risk of diabetes. (Genetic Lifehacks Diabetes Report)
A variant in the MC1R gene was also linked to reduced healthspan. MC1R encodes melanocortin, which is involved in skin and hair color as well as skin cancer. But, variants in the gene are also linked to increased susceptibility to certain pathogens.
Other immune system genes were also identified. Variants in the HLA genes were also linked to healthspan. The HLA-DQ1 gene has variants related to a number of autoimmune diseases, including type 1 diabetes and celiac disease.
Conclusion:
These healthspan genome-wide studies really drive home the importance of metabolic health (avoiding diabetes) and heart health. Additional signals indicate that the immune response is also essential to longevity.
Everyone has genetic variants that negatively impact healthspan. The key is figuring out what your kryptonite is — should you focus on Lp(a)? avoiding Alzheimer’s? making dietary choices to avoid diabetes? Focusing on what is more likely to impact your health makes a lot of sense.
If you haven’t done genetic testing, just knowing your family health history can help. If you want to do genetic testing, AncestryDNA is on sale this week for $39.