Background
Evidence indicates that the adverse health effects of obesity differ between genetically and environmentally influenced obesity . We examined differences in the association between obesity and cardiovascular disease (CVD) among individuals with genetically predicted low, medium, or high body mass index (BMI).
Methods
We used cohort data from Swedish twins born before 1959 whose BMI was measured at ages 40 to 64 years (midlife) or at age 65 years or older (late life), or both, and prospective CVD information from the registry. national. linkage until 2016. A polygenic score for BMI (PGSBMI) was used to define genetically predicted BMI.
Individuals with missing BMI or covariate data, or who were diagnosed with CVD at the first BMI measurement, were excluded, leaving an analysis sample of 17,988 individuals. We applied Cox proportional hazards models to examine the association between BMI category and incident CVD, stratified by PGSBMI. Co-twin control models were applied to adjust for genetic influences not captured by the PGSBMI.
Results
Between 1984 and 2010, 17,988 participants were enrolled in substudies of the Swedish Twin Registry. Midlife obesity was associated with increased CVD risk across all PGSBMI categories, but the association was strongest with genetically predicted lower BMI (hazard ratio 1.55 to 2.08 for those with PGSBMI high and low, respectively).
Within monozygotic twin pairs, the association did not differ by genetically predicted BMI, indicating genetic confounding not captured by the polygenic score for BMI (PGSBMI). The results were similar when obesity was measured in old age, but suffered from low power.
Interpretation
Obesity was associated with CVD regardless of polygenic score category for BMI (PGSBMI), but obesity influenced by genetic predisposition (genetically predicted high BMI) was less harmful than obesity influenced by environmental factors (obesity despite high BMI). low genetically predicted). However, additional genetic factors, not captured by the PGSBMI, still influence the associations.
Comments
The risk of developing cardiovascular diseases is lower in people with obesity who have a genetic predisposition to a high BMI than in people with obesity influenced mainly by environmental factors such as lifestyle, researchers from Karolinska Institutet report in eClinicalMedicine .
There has been a global increase in the incidence of overweight and obesity in recent years. Almost a third of the world’s population now lives with overweight or obesity.
“The figure is alarming as it is well established that a high BMI in middle age increases the risk of developing cardiovascular diseases and other conditions,” says Ida Karlsson, assistant professor at the Department of Medical Epidemiology and Biostatistics at the Karolinska Institutet.
However, according to this new study, the risk of developing cardiovascular disease varies widely among people with obesity. The researchers used data from more than 15,000 twins from the Swedish Twin Registry, gathering information about their BMI and their genetic predisposition to a high BMI. They also used data from medical records to establish the incidence of cardiovascular disease in this group.
By analyzing this information, researchers were able to study how overweight and obesity as a result of genetic versus environmental and lifestyle factors influenced the risk of cardiovascular disease.
“The link between obesity and cardiovascular disease was twice as strong in those with a genetic predisposition to low BMI than in those with obesity driven by genetic factors,” says the study’s last author, Ida Karlsson.
Dr. Karlsson emphasizes that a healthy lifestyle is always important for everyone, and that the risk of cardiovascular disease was higher in all people who were overweight or obese compared to people with a healthy weight. However, the findings also indicate that obesity driven primarily by genetic factors may not have the same adverse impact on health as obesity driven by other factors, such as lifestyle.
“Obesity is a complex common disease that can have many different causes.” "Because it is so stigmatized, the results may help us understand that its health effects differ from individual to individual."
She continues: “Although we all know that it takes more than exercise and diet to combat obesity, there is still a huge stigma associated with it. “I think a lot could be gained by focusing on what has caused obesity and what we can do to reduce the risk of comorbidities in each individual rather than focusing primarily on BMI.”
The next step of Dr. Karlsson’s research is to examine how people with overweight and obesity caused, respectively, by genetic and lifestyle factors differ in blood glucose levels, cholesterol and markers of inflammation .
Added value of this study
By considering phenotypic obesity together with a polygenic score for body mass index (BMI; PGS BMI), we examined differences in CVD risk between genetically predicted obesity and obesity driven primarily by nongenetic factors. For these purposes, we used a cohort of almost 18,000 Swedish twins followed on average for 18 years. In fact, there were differences, with the increased risk for those with obesity influenced by lifestyle or other environmental factors (obesity despite a low PGS BMI) being twice that of those with genetically predicted obesity (obesity with a low PGS BMI). high; risk rates 2.08 versus 1.55), compared to those with a healthy weight in the same PGS BMI category.
Implications of all available evidence
While a healthy lifestyle should always be strived for, findings from the current study and previous work indicate that obesity influenced by environmental factors may be more detrimental than obesity influenced by genetic factors . The topic has not yet been well studied, but this heterogeneity in obesity has been observed in several important outcomes and in data from Sweden and the US. This, together with the attenuated association within twin pairs, indicates that the effects Negative effects of obesity on health may be mediated by other factors, rather than being driven by obesity itself .
In conclusion , while it is important to note that overweight and obesity were associated with increased CVD risk across all PGS BMI categories, obesity influenced by environmental factors may be more detrimental than obesity influenced by genetic factors. . Interestingly, these differences were not observed when comparing pairs of monozygotic twins, indicating that there are shared environmental or genetic factors, not captured by the PGS, that influence the associations. |
Reference : “Genetically and environmentally predicted obesity in relation to cardiovascular disease: a nationwide cohort study.” Elsa Ojalehto, Yiqiang Zhan, Juulia Jylhävä, Chandra A. Reynolds, Anna K. Dahl Aslan, Ida K. Karlsson. eClinicalMedicine, online 6 April 2023, doi: 10.1016/j.eclinm.2023.101943
The study was mainly funded by the Swedish Research Council for Health, Working Life and Welfare (Forte) and the Strategic Research Area in Epidemiology and Biostatistics at Karolinska Institutet. The researchers report no conflicts of interest.
