Genetic Risk May Influence Weight Loss After Bariatric Surgery, Study Says

Bariatric surgery is the most effective treatment for morbid obesity, causing considerable weight loss, along with improvements in metabolic health and better survival.

It includes a range of procedures (e.g. gastric bypass, sleeve gastrectomy, adjustable gastric band, and biliopancreatic diversion with duodenal switch) aimed at restricting the amount of food the stomach can hold.

However, the amount of weight a person loses following surgery is quite variable. Some studies point to genetic differences as a possible cause, and some of those differences may come from variants known to predispose to excess weight or obesity.

Genetic risk scores are often calculated as the sum of variations found across a person’s genome (the entire set of genetic material, or DNA, inside our cells), associated with a certain trait.

They are created based on small variations within our DNA — called single nucleotide polymorphisms (SNPs) — found to occur more frequently in people with a particular attribute, such as excess weight.

The data is obtained from large genome-wide association studies (GWAS), used by researchers to pinpoint genes that may contribute to a person’s risk of developing a certain condition.

Using available genetic risk scores, a team led by researchers of Innlandet Hospital Trust, in Norway, and University of Copenhagen, in Denmark, set out to study the impact of genetic variations on bariatric surgery-induced weight loss.

Researchers tested three different genetic risk scores to see which was better at explaining weight loss in 577 patients two or three years after undergoing a Roux-en-Y gastric bypass. Patients were referred to two Danish hospitals. Their mean age was 45 years, and mean body mass index (BMI, a measure of body fat) was 44.4 kg/m².

One of the scores tested referred to risk of excess BMI in European populations; the two others were genetic risk scores of surgical weight loss.

On average, patients lost 76.9% of their excess weight (ranging from 21.7 to 149.2%) after surgery.

One of the scores was significantly associated with how much weight patients had lost. It was a genetic risk score for surgical weight loss created based on known BMI SNPs associated with surgery-induced weight loss.

Patients expected to have a high weight loss according to this score had lost 81.1% of their excess weight; those predicted to have the lowest weight loss had lost 73.9% of their excess weight — a difference of about 1.7 kg.

A difference score also indicated that patients genetically predisposed to low BMI had lower weight loss after bariatric surgery. The patients scoring the lowest had a weight loss of 68.8%.

In addition, the team identified 13 SNPs (among a total of 126 searched) known to be associated with being overweight (adiposity) that also related to weight loss variations among individuals.

“A genetic risk score was associated with [excess BMI loss] after bariatric surgery, but may not yet be applicable to clinical practice,” researchers said, adding that larger studies are needed to confirm the usefulness of this risk score.

In the future it may be possible to help clinicians choose treatment strategies for patients with morbid obesity, the researchers said. However, they stressed that even though knowing if the genetic risk of obesity also impairs the ability to lose weight is a question of clinical and biological interest, “in our study, high genetic risk for obesity did not hinder weight loss after bariatric surgery.”