Recent times has seen an influx in companies offering direct to consumer genetic tests that offer a wide range of feedback, including genetics-based nutrition. Nutrigenomics is the attempt to use genetic testing to steer dietary recommendations and now that many inexpensive mail-order genetic tests are available, could this be the answer to the obesity crisis?
Apparently not, according to Dr Ruth Loos from the Icahn School of Medicine at Mount Sinai.
While genetics does play a role in the onset of obesity, it is only one element of a much wider picture, and advice based on genetics alone has the ability to do more harm than good according to her recent talk at a virtual conference hosted by the American Nutrition society.
Loos explained that previous studies have shown that our genes contribute to around 40-70% of obesity risk, and only 30-60% comes from lifestyle. Obesity has around 1000 gene variants associated with it, and Loos questioned whether we have the evidence needed to provide diet advice based on a person’s genetics.
Putting nutrigenetic tests to the test
Dr Loos decided to sign up to one of the gene-based nutrition advice companies in order to get insight into the advice they give and the data behind that advice, and so presented the case study of a 48-year old healthy and active woman who does not need to lose weight but wants to live a healthy lifestyle. She received her results six weeks after signing up, and they told her that someone of her genotype is more likely than the average person to gain weight on a high saturated fat diet. The company provided Loos with data to back up the prediction that on her diet, with more than 22g of saturated fat a day, her BMI would be 6% higher than an individual with a different genotype. After checking the referenced studies by Corella. D., et al, and studies that showed her genotype group compared with two other genotype groups predicted her group to go up much quicker on a high saturated fat diet than the other groups.
However, Dr Loos said she had concerns with companies using this information to predict weight gain. She said the data she was presented with is not data on weight gain, it does not show that weight will increase by eating a high saturated fat diet, it is simply cross-sectional information. It was also only one variant, whereas other variants could create the opposite effect.
She also voiced concerns about what this might mean for people with other genotypes. Her genotype was in the unlucky group that was predicted a higher BMI from a high saturated fat diet, but what about the other groups? Is it possible to tell them that they will not gain as much weight following a similar diet? That may not be a safe message as it may not affect their weight, but it could still affect their risk of cardiovascular and other diseases.
Likewise, the same researchers that were referenced did a third study which included observations of the people in the previous study and found that the observations from all three genotype groups completely overlapped, meaning this data was not suitable for prediction.
So, can genetics really predict obesity?
Last year, a study created a polygenic score to predict who was most at risk of developing obesity from data of 2.1 million variants on a polygenic risk score. While this study received a lot of attention from the media and led to the launch of an inexpensive test for people to predict their risk of obesity, Loos questioned the validity of the test.
She argues that in order for a predictive test to have clinical relevance, it must have an area under the curve of 0.80 or higher, and if a test had an area under the curve of around 0.50, then it is about as predictable as “flipping a coin”. The study never published the data for the area under the curve, and so she calculated this herself, which came to just under 0.64, which was “far off clinical utility”.
Loos’ concerns come from the advice that goes to people who are told their risk of obesity is not high, which could put them at risk.
But what about using genetics to guide nutritional advice?
There have been studies that have done genotype profiling for 23 diseases on nearly 3,700 participants, where they were asked about their weight, diet, exercise, and anxiety, and followed up after three months and at one year. The team found that those who had been warned to make nutritional changes to their diet based on their genes were more likely to increase their fat intake at their three-month follow ups.
Loos explains that this is understandable as these participants are likely to think their genetics underpin their weight and are demotivated to follow a healthy diet.
Overall, despite research advancing our understanding of how our genes influences our weight and nutritional health, currently nutrigenetic tests should be taken with a pinch of salt to make dietary decisions. Loos states that “we need longitudinal studies to see how people respond to certain diets. Lifestyle behaviour is hard to change so just informing people of genetic risk will not necessarily have the outcome you wish for”.
