Under the direction of experts from the Medical Research Council (MRC), the study found genetic polymorphisms in two genes that affect the risk of obesity in some of the most significant ways yet found.
According to experts, uncommon mutations in the APBA1 and BSN genes were among the first to be linked to obesity and show an increased risk only in maturity.
The MRC Metabolic Diseases Unit’s Professor Giles Yeo, one of the study’s authors, stated: “We have identified two genes with variants that have the most profound impact on obesity risk at a population level we’ve ever seen, but perhaps more importantly, that the variation in Bassoon is linked to adult-onset and not childhood obesity.”
“Thus these findings give us a new appreciation of the relationship between genetics, neurodevelopment and obesity.”
The researchers performed whole exome sequencing (a sort of DNA sequencing used to determine what may be causing symptoms or a disease) of body mass index (BMI) in over 500,000 individuals using data from the UK Biobank and other sources.
They discovered that there is a six-fold increase in the risk of obesity due to genetic variations in the BSN gene, also referred to as Bassoon.
Additionally, it was linked to a higher risk of type 2 diabetes and non-alcoholic fatty liver disease.
One in 6,500 adults were discovered to be affected by the Bassoon gene variations, indicating that approximately 10,000 persons in the UK may be affected.
“These findings represent another example of the power of large-scale human population genetic studies to enhance our understanding of the biological basis of disease,” stated study author and MRC investigator Professor John Perry of the University of Cambridge.
“The genetic variants we identify in BSN highlight a new biological mechanism regulating appetite control and confer some of the largest effects on obesity, type 2 diabetes, and fatty liver disease observed to date.”
Heart disease and type 2 diabetes are two major diseases for which obesity is a major risk factor.
It’s unclear, though, just why some people are genetically predisposed to gaining weight.
In contrast to the obesity genes found in earlier research, variations in BSN and APBA1 do not correlate with childhood obesity.
Because of this, the researchers thought they might have discovered a novel biological explanation for obesity.
Drawing from extant literature and their in vitro investigations, the authors propose that age-related neurodegeneration may be influencing appetite regulation.
Using genetic data from individuals in Pakistan and Mexico, the researchers collaborated closely with AstraZeneca to reproduce their findings in pre-existing groups for the current study.
This is significant because it allows the researchers to extend their findings to individuals who are not of European descent.
