Previously, genetic screening has only been conducted through healthcare providers, warranted on medical grounds. Now, in an age where advanced high-throughput-omic technologies allow for cheaper and faster screening of the genome, consumer genomics is becoming increasingly mainstream and a growing number of people are opting to purchase genetic tests for a variety of purposes, including personalized nutrition advice.
Interplay between genetics and nutrition
The increasing volume of nutrition and wellbeing advice published in the media can be challenging to digest and makes it difficult to deduce exactly what makes a diet “healthy”. Nutrigenetics and nutrigenomics are branches of science that have been propelled by the Human Genome Project (HGP) and aim to identify how we respond to nutrients based on our genetic profile (nutrigenetics) and how the foods that we eat affect our genome (nutrigenomics). Variation at the genetic level, the most common form being single nucleotide polymorphisms (SNPs), produce variations in the molecular machinery involved in nutrient metabolism across populations. Subsequently, different people show varied metabolic responses to the same foods.
The HGP has provided leverage for this field in that large sequence databases are freely available, listing thousands of SNPs that have been identified thus far and their impact on human physiology. An array of companies such as DNAFit and Nutrigenomix utilize this information to provide personalized nutrition and diet advice, often available at the click of a button. “If you can gain insight into your own genetic predispositions, it’s clear that you can make better decisions in order to maximize your health and fitness,” says Avi Lasarow, CEO of DNAFit, a personalized health and wellbeing company formed in 2013.
Dr. Ahmed El-Sohemy, PhD, Canada Research Chair in Nutrigenomics, discusses the evidence and application of the science of nutrigenomics. Taken from YouTube.
From saliva swab to SNP profile
In direct-to-customer testing (DTC), obtaining a genetic profile couldn't be easier. “The kits are simple to use, and, in most cases, you are required to deposit a saliva sample in a tube, seal it, and post it back to the company,” says Yiannis Mavrommatis, Senior Lecturer in Nutrition at St Mary's University. What happens next behind the scenes is the result of decades of developments in genetic technology. “Your sample is then sent to a laboratory where your DNA is extracted from saliva and genotyped for the SNPs that the specific company has chosen to include.”
Similarities and differences exist across companies and institutions in their approaches to screening. Mavrommatis says, “The most common methods that are used in SNP genotyping are KASP assays and SNP microarrays. Whole genome sequencing and exome sequencing are more exhaustive and are also used in research but only within large projects due to their cost and the large data that they generate. PCR-based techniques are also popular in candidate-gene studies where only a small number of specific SNPs needs to be genotyped.”
In nutrition and genetic testing, the outcome of your report is dependent on the SNPs that the company or institution select to screen against. DNAFit, for example, as part of its “Diet Pro” package screen a variety of SNPs to produce reports analyzing factors such as an individual’s carbohydrate and fat response, caffeine, alcohol and salt sensitivity, lactose tolerance, and celiac predisposition.
What insight can our genetics provide?
Nutrigenomix is the first genetic testing company to provide personalized nutrition reports used exclusively for healthcare professionals only. Ahmed El-Sohemy, PhD, the founder of Nutrigenomix, emphasizes that understanding our genetic profile can help us to make informed choices about the food and drink we consume – choices that may ultimately affect our health. For instance, in the study published by Nutrigenomix researchers in JAMA, the clinical implications of being homozygous for the CYP1A2*1A allele, and thus a “fast” caffeine metabolizer, vs carrying a variant, CYP1A2*1F and being a “slow” caffeine metabolizer, in a sample of 2,014 people was explored.1 “We showed that individuals who are "slow" metabolizers of caffeine have an increased risk of heart disease, whereas "fast" metabolizers actually see the opposite effect and it may have protective benefits,” says El-Sohemy. Subsequent research has confirmed these findings.2
Genetics can also give insight into how much of a specific nutrient or vitamin your body requires as its "standard" – an example being the GSTT1 gene and response to vitamin C. "Having a particular version of this gene means your vitamin C requirements differ. The "risk" variant of this gene is found in about 20% of Caucasians, but in roughly half of East Asians. Regardless of what your genetic ancestry is, you still need to know if you, as an individual, have that risk variant. There are other examples of other genetic variants that are common in various populations around the world,” adds El-Sohemy.
Informed exercise choices to avoid injury
Insights aren't only limited to nutrition, but also can help you make informed exercise choices. Sporting injuries tend to occur when force is applied that exceeds the strength of the body part being exercised. However, injury can also result from underlying medical conditions or weakness in the muscles, bones, and joints. Typically, we only learn of our susceptibility to injury once the injury itself has been sustained. But what if injury could be avoided in the first place?
“At DNAFit, we look at genes that are linked to the production of collagen, which is the main structural component of ligaments and tendons,” says Lasarow. “Variations in these genes have been linked to an increased risk of Achilles tendon, knee tendon, and shoulder injuries. As a result, if we identify a person with these genetic variants, we can give them advice on how best to mitigate this risk. This might be increasing the amount of specific shoulder strengthening work a person does, or by introducing eccentric loading exercises for those at an increased risk of an Achilles tendon injury”.
Clinical applications of nutrition and genetics research
The World Health Organization (WHO) statistics estimate that in 2016, 1.9 billion adults over 18 were overweight, with 650 million defined as clinically obese. Genome wide association studies (GWAS) examine genetic variations across large populations. In a study published in Science, researchers conducted a whole-genome scan of DNA samples obtained in the Framingham Heart Study, where they discovered a variant 10kb upstream of the insulin-induced gene-2 (INSIG2) associated with obesity.3 More recently, a study published by the GIANT consortium identified 24 coding loci – 15 common and nine rare – across the chromosomes in 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation) that predisposed them to a higher waist-hip ratio.4
The whole picture is significantly more complex than one single gene controlling a person’s likelihood of obesity – interplay between genetics, environmental factors, and lifestyle certainly exist. However, novel insights gained through personalized nutrition research may provide a much needed shift in the paradigm that a single diet is applicable to the entirety of the population: “When we consider that public health initiatives in nutrition (one size fits all approach) have been consistently failing to meet their targets, the personalized approach has the potential to substantially improve nutrition attitude,” says Mavrommatis.
Overcoming challenges in a novel field
As with any scientific field in its infancy, nutrition and genetics faces challenges that it must overcome. "There are no clear scientific, ethical or commercial frameworks specific to nutrition and genetics. As a result, there are growing concerns about data protection and scientific rigor. A good example is related to the number of SNPs that each company analyses. Some companies (the more responsible ones) only genotype a small number of SNPs that are supported by appropriate science and communication of results is done by having experts explaining probabilities, risks and interactions with environment factors. At the same time (and due to lack of regulations), a substantial number of DTCs include SNPs, sometimes hundreds of them, which may only have very little clinical value," says Mavrommatis. "An international project led by the Quadram Institute in the UK is currently ongoing and its aim is to provide a platform for evidence-based personalized nutrition services. It is still early days, but this is a promising initiative.”
Nonetheless, researchers are excited to see where this field will go: "What we have here is a dream combination: on one hand we have DNA, the epitome of biological science, the most magical and powerful molecule. On the other hand, we have nutrition, the most potent, modifiable environmental factor (we all have to eat and drink many times every day). The fact that these two work together and we now start to understand this relationship, will reshape nutrition science," Mavrommatis concludes.
2. Palatini, P., Ceolotto, G., Ragazzo, F., Dorigatti, F., Saladini, F., Papparella, I., Mos, L., Zanata, G. and Santonastaso, M. (2009). CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. Journal of Hypertension, 27(8), pp.1594-1601.
3. Herbert, A. (2006). A Common Genetic Variant Is Associated with Adult and Childhood Obesity. Science, 312(5771), pp.279-283.
4. Justice et al. 2019. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution. Nature Genetics. DOI: https://doi.org/10.1038/s41588-018-0334-2.