And other factors like lifestyle, biological and environmental just influence appetite and make you fat.
resh research has now identified a set of genes that have been found to impact the likelihood of obesity based on age and sex.
This study, published today in the journal Cell Genomics, may offer insights into previously unknown biological pathways that promote obesity while emphasizing how factors like age and sex play significant roles in health and disease.
John Perry, the study’s lead author and a professor of genetics at the Wellcome-MRC Institute of Metabolic Science, University of Cambridge, U.K., says, “There are a million and one reasons why we should be thinking about sex, age, and other specific mechanisms rather than just lumping everyone together and assuming that disease mechanism works the same way for everyone.
“We’re not expecting people to have completely different biology, but you can imagine things like hormones and physiology can contribute to specific risks.”
The researchers scrutinized the role of sex in obesity risk by analyzing the exome, the part of the genome that encodes proteins, of 414,032 adults involved in the UK Biobank study. They investigated gene variants linked to body mass index (BMI)—a measure of obesity derived from height and weight—in both men and women. This led to the discovery of five genes that impact BMI in women and two in men.
Notably, malfunctioning variants of three genes—DIDO1, PTPRG, and SLC12A5—correlated with increased BMI in women, with negligible impact on men. More than 80% of women carrying DIDO1 and SLC12A5 variants were found to be obese, as per their BMI. Individuals with DIDO1 variants exhibited strong connections with high testosterone levels and an increased waist-to-hip ratio, both of which are indicators of risk for obesity-related health issues like diabetes and heart disease. Those carrying SLC12A5 variants had a higher risk of type 2 diabetes. This reveals the roles of previously unidentified genes in obesity development in women, without a similar effect on men.
To study the influence of age on obesity, Perry and his team replicated their process by looking for gene variants linked to body size during childhood. This led to the identification of two genes, OBSCN and MADD, which have not been associated with childhood body size or fat content before. While OBSCN variant carriers were more likely to be overweight in childhood, those with MADD variants were found to be leaner. Interestingly, MADD genetic variants did not correlate with adult obesity risk, showcasing the effect of age-specific factors on body size.
“What’s quite surprising is that if you look at the function of some of these genes that we identified, several are clearly involved in DNA damage response and cell death,” explains Perry.
Obesity is predominantly associated with brain functions, while both biological elements and environmental circumstances play significant roles in regulating hunger.
“There’s currently no well-understood biological paradigm for how DNA damage response would influence body size. These findings have given us a signpost to suggest variation in this important biological process may play a role in the etiology of obesity.”
They are now planning to validate their study with a larger, more diverse sample. They also aim to delve deeper into the function of these genes and their connection with obesity using animal models.
Perry concludes, “We’re at the very earliest stages of identifying interesting biology. We hope the study can reveal new biological pathways that may one day pave the way to new drug discovery for obesity.”
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