CVD risk highest among adults with obesity and genetically predicted low BMI
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Key takeaways:
- The risk for CVD is higher among adults with a low polygenic score for BMI than those with a high polygenic score.
- CVD risk between polygenic score groups was similar among monozygotic twins.
Adults with a genetically predicted high BMI may have a lower risk for cardiovascular disease than those whose obesity is linked more to environmental factors, according to a study published in eClinicalMedicine.
In findings from Sweden of midlife and late-life adult twins, obesity was associated with an increased risk for CVD across the entire range of polygenic scores from BMI. However, midlife adults with a genetically predicted low BMI had the highest CVD risk.
“Individuals with obesity have a higher risk for CVD, but this risk is less elevated for obesity resulting to a large extent from genetic predisposition,” Ida K. Karlsson, PhD, assistant professor in the department of medical epidemiology and biostatistics at Karolinska Institute in Sweden, told Healio. “Obesity is a complex disease, and we do not yet understand why, but it is plausible that individuals with genetic predisposition to a high BMI can cope better with having a higher weight.”
Researchers collected data from the Swedish Twin Registry of nearly all twins born in Sweden in 1958 or earlier who had genotyping data available. CVD, stroke and non-stroke CVD outcomes were collected from the National Patient Registry and the Cause of Death Registry. BMI was collected for each participant, with midlife BMI including adults aged 40 to 64 years with a BMI measurement, and late-life BMI including adults aged at least 65 years with a measurement available. A polygenic score for BMI was calculated using a recent genome-wide association study that identified 941 genetic variants associated with BMI. The cohort was categorized as having genetically predicted low, medium or high BMI based on polygenic score.
CVD risk higher with genetically predicted low BMI
There were 17,988 adults included in the study, of whom 15,786 had BMI measured in midlife and 5,488 had BMI measured as older adults, with some adults having measurements in both age categories. Of the midlife group, 3,123 adults were diagnosed with CVD, 2,414 adults were diagnosed with non-stroke CVD and 1,156 were diagnosed with stroke. Among late-life adults, 1,681 were diagnosed with CVD, 1,246 were diagnosed with non-stroke CVD and 831 were diagnosed with stroke.
In independent effect models, midlife obesity increased the risk for CVD by 76%, and 1 standard deviation (SD) increase in polygenic score for BMI increased CVD risk by 12%. Compared with adults with obesity and a mean polygenic score for BMI, adults with obesity had a 14% lower risk for CVD with each 1 SD higher polygenic score. Adults with a genetically predicted low BMI had a 2.08 times higher risk for CVD compared with a 1.55 times higher CVD risk for adults with genetically predicted high BMI.
No difference in CVD risk for monozygotic twins
Researchers conducted a co-twin control analysis to adjust for genetic influences that may not be captured by the polygenic score. Among monozygotic twins, the difference in CVD risk between the polygenic score groups disappeared. Among dizygotic twins, the associations between genetically predicted BMI and CVD risk were similar to what were observed in the full cohort.
“It was a little surprising at first that we did not see this difference between genetically versus environmentally predicted obesity when comparing identical twins,” Karlsson said. “However, this is the beauty of the twin design, it can control for unmeasured confounding factors that we usually cannot account for. In this case, it tells us that genetic factors, other than those predicting BMI, explain the association between obesity and CVD.”
According to a related press release, future research will look at how blood glucose, cholesterol and inflammation markers differ among adults with genetically predicted high BMI and those with a genetically predicted low BMI.
“Obesity is a heterogeneous phenotype, which can have different causes as well as consequences,” Karlsson said. “We are not there yet and first need to understand the disease better, but in the long run I hope we can move away from focusing on BMI and look at what has caused the obesity and how we best can limit the risk of comorbidities in each individual.”
Reference:
- People with obesity due to genetic predisposition have lower risk of cardiovascular disease. https://news.ki.se/people-with-obesity-due-to-genetic-predisposition-have-lower-risk-of-cardiovascular-disease. Published April 6, 2023. Accessed April 6, 2023.
For more information:
Ida K. Karlsson, PhD, can be reached at ida.karlsson@ki.se.
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