Genetic Risk for High BMI Linked to Obesity, Metabolic Problems in Adults, Study Suggests

Genetic Risk for High BMI Linked to Obesity, Metabolic Problems in Adults, Study Suggests

Middle-age and older people who have a greater genetic risk for high body mass index (BMI) are significantly more likely to be overweight or obese and are more susceptible to metabolic dysfunction, a study suggests.

The study, “Genetic scores for BMI related to metabolically unhealthy obesity in an older Chinese population,” was published in the journal Clinical Endocrinology

Recent reports have suggested that genetic factors can explain between 40% and 70% of people’s BMI, a measure of weight and height. These findings were based on genome-wide association studies (GWASs) that identified genetic markers linked to weight gain and obesity.

These genetic markers – known as single nucleotide polymorphisms (SNPs) — are variations in a single nucleotide, the building blocks of DNA. SNPs can be identified by screening a person’s entire genome and then can be used to calculate a genetic risk score (GRS) for obesity. A higher number of obesity-linked SNPs means a higher GRS.

Large-scale SNP analyses have primarily focused on people of European descent, with studies in East Asian populations reporting differences in some obesity-linked SNPs. However, these studies mostly addressed children and adolescents.

Researchers in China addressed this gap by conducting a large-scale genetic analysis using data from the Guangzhou Biobank Cohort Study (GBCS), an ongoing study of environmental and genetic factors of chronic diseases in people 50 and older and living in Guangzhou.

They collected information on age, gender, education, and tobacco and alcohol use. Height, weight, waist circumference, blood pressure, and heart and lung function were measured. Participants were also asked to compare their weight with that of their peers at age 20. 

Blood was collected to analyze fasting plasma glucose, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. Initial, or baseline, measurements were determined between 2003 and 2008, and patients had follow-ups between 2008 and 2012. 

A total of 13,597 patients, at an average age of 61 years, were evaluated. Of these, 10,877 were women and 2,720 were men. Based on the standards for Chinese populations, 6,175 participants were considered overweight (BMI of 24 or higher). A GRS associated with BMI was calculated for each patient based on 12 obesity-linked SNPs.

Results showed that patients with a high GRS were 36% more likely to be overweight at baseline and 34% more likely at follow-up. Likewise, people with a high GRS were also more likely to be obese (BMI of 28 or higher in Chinese populations), 56% at baseline and 49% at follow-up.

Participants in the high GRS group were also at a higher risk for sustained excess weight and obesity.

Compared with their peers, people in the high GRS group were 30% more likely to be overweight at 20 years of age than those in the low GRS group. 

In contrast, GRS was not associated with being newly overweight or obese, as assessed by BMI at follow-up.

Researchers then split the participants into two groups — obese patients who were metabolically healthy and those who were metabolically unhealthy (MUO). A patient was considered metabolically unhealthy if he or she had at least three of the following risk factors: high waist circumference, high blood pressure, low levels of HDL cholesterol, or high amounts of triglycerides and fasting glucose.

Participants in the high GRS group were more likely to be metabolically healthy than those in the low GRS group: 51% at baseline and 35% at follow-up.

The risk of being metabolically unhealthy in the high GRS group was 59% at baseline and 56% at follow-up. Those with a high genetic score were 28% more likely to become metabolically unhealthy at follow-up than those in the low GRS group. 

“The participants with a high GRS were more likely to be overweight/obese at baseline and follow-up and were heavier than their peers at the age of 20 years,” the researchers wrote. “We also found a positive association between the GRS and newly MUO individuals.” 

“Participants with a high GRS need to prevent becoming obese when they are younger and should be more aware of metabolic disorders when they are older,” they added.

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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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