Prevention

5.3.4 Personalised prevention & genotyping

Despite decades of interventions at national level, most nations have not achieved progress in reversing the increasing tide of lifestyle related risk factors such as obesity and diabetes. The use of generalisations, such as calories, number of steps, minutes of exercise etc, without taking the individuals’ life circumstances into account has not had the desired impact on lifestyle change, with a large intention-action gap as discussed earlier in the document. One reason for this is that individuals possess different capabilities and motivations to change (Hardcastle et al., 2015) and provision of a prevention approach that is personalised to such factors is more likely to lead to greater impact at individual and population level.

The Impact of Personalisation on Healthspan and Lifespan

There are numerous benefits of personalised interventions for lifestyle change:

• Personalised interventions are more effective than generic interventions at promoting change across a range of lifestyle behaviours
• Tailoring support to individuals’ needs, experiences, and expectations can boost patient satisfaction with health services
• Personalisation enhances the relevance of lifestyle change support resources, so enhancing engagement and adherence

While tailored advice and support has always been offered by healthcare providers, the advent of digital health technologies means that precision prevention services can now be offered at sufficient scale to benefit population health.

Genetic and Epigenetic Information

Currently, when we refer to personalisation or precision medicine, we rely very heavily on the use of genotyping information.

1. Clinical Utility

To date there has been modest clinical utility from genotyping output, aside from a handful of hereditary conditions which are discussed below.

Cancer detection and management has the potential to be transformed via genetic information. Detection of the BRCA mutation for breast cancer, which not only alters risk, but the screening and management of the disease, was one of the earliest clinical use-cases for genetic information. In cervical cancer, the identification of specific genetic polymorphisms linked to cervical cancer susceptibility, can facilitate more personalized screening and preventive measures.

Huntington’s Disease is a critical condition where genetic information plays a central role, impacting treatment decisions and prognostic assessments. Genetic information can inform both diagnosis and the timing of potential therapeutic interventions.

2. Polygenic Risk Scores

More recent interest has been in the elucidation of polygenic risk scoring – the amalgamation of risk that accrues from numerous genetic locations – from individuals’ genotyping data to predict the risk of chronic disease. However, this theory has not been well supported by the evidence, which shows very low correlation between predicted disease rates from polygenic risk scoring and actual disease incidence (Hingorani et al., 2023).

3. Epigenetic Information

Epigenetic information acts as a crucial link between our genes and our environment, influencing how our DNA is expressed without changing its underlying sequence. It involves chemical modifications like DNA methylation and histone modification that essentially act as switches, turning genes “on” or “off.” Over time, factors like diet, exercise, stress, and toxin exposure can lead to disruptions in these patterns, called “epigenetic noise” which can lead to the development of chronic diseases such as cancer, diabetes, and cardiovascular disease.

Genetic susceptibility in Alzheimer’s disease (AD) primarily involves the APOE gene, specifically the ε4 allele, which significantly increases the risk of late-onset AD. The presence of the ε4 allele can guide discussions regarding lifestyle interventions, which can heavily influence the progression to clinical Alzheimer’s disease, as well as potential enrolment in clinical trials for preventative therapies.

Regular physical activity induces favourable epigenetic modifications, particularly in muscle tissue. For example, it can promote DNA demethylation and alter histone marks on genes related to glucose and lipid metabolism, as well as cellular repair and inflammation, thereby improving insulin sensitivity and chronic low-grade inflammation. The type and intensity of exercise can have specific impact, with high intensity interval training and resistance strength training both shown to partially act through epigenetic changes.

Our nutrition provides the raw materials for the enzymes that add or remove epigenetic tags. For instance, diets rich in fruits, vegetables, and whole foods provide antioxidants and other bioactive compounds that can influence DNA methylation and histone acetylation. The Mediterranean diet, known for its anti-inflammatory properties, is a prime example of a dietary pattern that can promote beneficial epigenetic changes, leading to improved health biomarkers and slower epigenetic aging. Conversely, unhealthy diets high in salt, sugar and saturated fats can lead to detrimental epigenetic modifications that promote inflammation and disease.

Longevity-associated genes, such as the FOXO gene family, demonstrate the interplay between genetics and epigenetics. While some genetic variants of FOXO3 are associated with a longer lifespan, the expression and activity of these genes are heavily influenced by epigenetic factors – they respond to environmental stress by turning on genes related to stress resistance, DNA repair, and metabolism. Lifestyle interventions such as exercise and healthy nutrition can activate FOXO genes, allowing them to better perform their protective functions.

4. Pharmacogenomics

In pharmacogenomics, genotyping provides insights that can optimize drug therapy and reduce adverse drug reactions. For example, in individuals undergoing percutaneous coronary interventions, genotyping information aids in determining the appropriate use of clopidogrel, given that certain genotypes are associated with an increased risk of adverse cardiovascular events (Ramesh et al., 2020).

5. Application of Technology with Genetic Information

Merging electronic medical records with genetic risk profiles underline a growing trend in personalized medicine for neurodegenerative diseases. For example, a program aimed at utilizing electronic health records to stratify risk for Alzheimer’s disease based on genotypic data, showcases how such approaches bolster early intervention opportunities (Fosnacht et al., 2017).

The applicability of genetic analysis extends beyond traditional therapeutic or preventive paradigms. The Genotype-Tissue Expression (GTEx) Project illustrates the promise of correlating genetic data with biological outcomes, informing both diagnostic and treatment strategies for various conditions (Carithers et al., 2015). This comprehensive analysis enhances the understanding of disease mechanisms and enables tailored healthcare approaches based on individuals’ genetic profiles.

Such applications of genetic data exemplify the future trajectory of integrated healthcare models utilizing genotyping information for optimal patient management. Several barriers still hinder the widespread implementation of genomic-based precision medicine, including physicians’ knowledge gaps about genetics and the challenges of integrating genetic information into clinical practice (Najafzadeh et al., 2013). System-level changes are necessary to prepare healthcare providers to effectively use genetic data in patient care.

Personality and Psychological Factors

Conventional public health approaches typically only regard lifestyle without factoring in the individual factors that predispose to lifestyle behaviours such as mindset, personality, personal life circumstances, preferences and interests.

There are many different approaches to precision prevention of interventions. While demographic, health status, and exposure-based options are already commonly used, more novel approaches are beginning to emerge. For example, behavioural approaches involve specifically understanding how a health-related behaviour is enacted and developing targeted change programs based on this insight.

Similarly, psychological profiling, segmentation and tailoring offers another new approach, going further upstream to identify the individual psychological characteristics that drive health behaviours. Examples include health-related attitudes, social norms, perceived behavioural control and intentions, autonomy, competence, and relatedness in relation to health behaviour change (Taylor et al., 2006).

Furthering this approach, precision prevention programmes are now being developed based on personality type, such as using the ‘big five’ model. This follows from a growing evidence-base to show that personality traits are significantly associated with health behaviours (Strickhouser et al., 2017). For example, higher extraversion and neuroticism, and lower levels of conscientiousness have been linked to greater probability of smoking, increased alcohol intake, and physical inactivity. These additional insights enable prevention programmes to meet personality preferences, thereby enhancing programme engagement and satisfaction, and downstream efficacy as a result (Alqahtani et al., 2022).

Dietary Supplementation

Personalization in supplementation involves tailoring dietary intake and supplements to fit individual genetic, metabolic, and lifestyle factors. Nutrigenomics explores how individual genetic variations influence responses to dietary supplements. a tailored approach to supplementation could optimize nutrient intake based on one’s genetic background and metabolic needs, thus enhancing health benefits (Meral et al., 2024). Similarly, the evolution of nutrigenomics allows healthcare providers to use genetic assessments to recommend specific vitamins and minerals that align with a patient’s genetic makeup, potentially leading to more effective nutrient interventions.

1. Genetic Personalization of Supplementation

A prime example of personalized supplementation is for individuals with a Methylenetetrahydrofolate reductase (MTHFR) gene mutation. This common genetic variant can impair the body’s ability to convert synthetic folic acid (found in many fortified foods and supplements) into its active form, L-methylfolate. A personalized approach would recommend supplementing with the pre-methylated, active forms of folate (L-methylfolate or 5-MTHF) and vitamin B12 (methylcobalamin), bypassing the need for the impaired MTHFR enzyme.

2. Environmental & Lifestyle Personalization of Supplementation

Environmental and lifestyle factors also play a significant role in supplementation.

Sunlight Exposure: People with limited sun exposure, living in northern latitudes, or with darker skin tones may be at a higher risk of vitamin D deficiency. A personalized recommendation would include a higher dose of vitamin D3 to compensate for the lack of sun-induced synthesis.

Pollution: Exposure to air pollution, heavy metals, and other toxins can increase oxidative stress in the body. Personalization in this case would focus on supplements that support detoxification pathways and provide a high level of antioxidant support, such as N-acetyl cysteine (NAC), glutathione, and certain vitamins and minerals (zinc, selenium, vitamins C and E).

Diet: A vegan or vegetarian diet might require supplementation with nutrients not easily obtained from plants, like vitamin B12, iron, and omega-3 fatty acids. Conversely, someone who consumes a lot of oily fish might not need an omega-3 supplement.