Genetically Influenced Obesity Less Harmful Than Environment-Influenced Obesity

While the negative health effects of obesity in midlife are well-established, the causes and consequences of overweight or obesity in late-life may be more complicated.

Adverse health effects of obesity differ between genetically influenced obesity and environmentally influenced obesity, according to study results published in eClinicalMedicine.

Researchers examined differences in the association between obesity and cardiovascular disease (CVD) between individuals with a genetically predicted low, medium, or high body mass index (BMI). A total of 17,988 participants enrolled in the Swedish Twin Registry participants between 1984 and 2010 were included in the study. Participants were born prior to 1959 and had BMI measured between the ages of 40 to 64 years (mid-life), at age 65 years and older (late-life), or both categories. Prospective CVD information was gathered using nationwide data through 2016.

A total of 15,786 individuals had BMI measured in midlife and 5488 had BMI measured in late-life. There were 3286 participants who had measures taken in both age categories. The midlife sample included 5144 complete twin pairs (dizygotic pairs, n=3124; monozygotic pairs, n=2020). The late-life sample included 1670 complete twin pairs (dizygotic pairs, n=1235; monozygotic pairs, n=435).

The effect estimates of obesity on CVD risk was attenuated in co-twin control analyses compared with the full sample, with a stronger attenuation within monozygotic (HR, 1.14; 95% CI, 0.64–2.02) than dizygotic (HR, 1.64; 95% CI, 1.11-2.42) twin pairs. The association between overweight and CVD was similar to that in the total population in dizygotic twin pairs (HR, 1.35; 95% CI, 1.10-1.66), but attenuated in monozygotic twin pairs (HR, 1.08; 95% CI, 0.80-1.46)

Importantly, this indicates that the negative health effects of obesity may be influenced by other factors, rather than by the obesity in itself….

The association between midlife obesity and CVD was stronger among women than men, but the associations between overweight or obesity and CVD were present in both women and men. The association between late-life BMI category was stronger within dizygotic (overweight, HR, 1.30; 95% CI, 0.97-1.74; obesity, HR, 1.42; 95% CI, 0.92-2.21) and monozygotic (overweight, HR, 1.54; 95% CI, 0.79-3.03; obesity, HR, 2.18; 95% CI, 0.68-7.02) twin pairs.

In the independent effect models, midlife overweight and obesity were associated with a 31% and 76% higher risk for CVD, respectively. One SD higher polygenic score for BMI was associated with a 12% higher risk for CVD.

Overall, obesity influenced by genetic predisposition (ie, genetically predicted high BMI) was less harmful than obesity influenced by environmental factors such as lifestyle, although the lifestyle factors that influenced obesity were not specified.

The study was limited by the self-reported BMI measures and historical effects of the included cohorts (ie, lifestyles and treatment options have changed during the large time span of when the twins were born).

“Importantly, this indicates that the negative health effects of obesity may be influenced by other factors, rather than by the obesity in itself, as we would otherwise expect similar effects of obesity, regardless of if it is predicted by genetic predisposition or environmental factors,” the researchers conclude.


Ojalehto E, Zhan Y, Jylhävä J, et al. Genetically and environmentally predicted obesity in relation to cardiovascular disease: a nationwide cohort study. eClinicalMedicine. 2023;101943. doi:10.1016/j.eclinm.2023.101943