European Association for the Study of Diabetes
European Association for the Study of Diabetes
September 17, 2014
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Genetic susceptibility tied to high BMI at all ages

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An increased risk of having a higher BMI at young, middle and old age is associated with a genetic risk score composed of variants from 31 BMI-associated DNA regions, according to research presented at the 50th European Association for the Study of Diabetes Annual Meeting.

The data also suggest that the genetic risk score (GRS) was associated with unstable weight from young to middle age and gaining substantial weight until middle age.

“Our findings propose that mechanisms underlying the susceptibility to obesity may have opposite consequences for weight gain before and after middle age,” Gull Rukh, a PhD student at the Lund University Diabetes Center in Sweden, said in a press release. “The mechanisms behind this switched associated effect are unknown and could not be addressed in our study, but they may be related to the more intensive weight gain before middle age among individuals with a high number of BMI-associated genetic variants, which could ultimately lead to weight loss due to, for example, higher morbidity and accentuated loss of muscle mass in old age. This needs to be verified in future studies.”

Gull Rukh

Gull Rukh

Rukh and colleagues evaluated 21,407 adults with self-reported BMI at young age (20 years) and measured BMI at middle age (mean age, 58 years), as well as 2,673 of those at old age (mean age, 73 years), to determine the effect of genetic susceptibility on BMI at young, middle and old age, and substantial weight gain over 50 years.

Researchers also analyzed the risk, per GRS quintile, for belonging to the reported unstable weight group and substantial weight gain from young, to middle, to old age, and from middle to old age.

A higher BMI was associated with GRS at all ages: 20 years (beta=0.03), middle age (beta=0.23) and old age (beta=0.2). There was a 10% increased risk per GRS quintile for having unstable weight associated with GRS from age 20 years to middle age (OR=1.1; 95% CI, 1.07-1.13) and a 4% increased risk for substantial weight gain (OR=1.04; 95% CI, 1.02-1.07).

Compared with participants in the lowest GRS quintile, those in the highest GRS quintile had a 42% increased risk for unstable weight and 15% for substantial weight gain. However, GRS was not associated with substantial weight gain from age 20 years to old age (OR=0.97; 95% CI, 0.9-1.05) and was associated with a 10% decreased risk for substantial weight gain from age 20 years to old age (OR=0.9; 95% CI, 0.84-0.97), as well as a 26% decreased risk when comparing the highest and lowest GRS quintiles (OR=0.74; 95% CI, 0.55-1.01).

“Our results suggest that the genetic effects related to higher BMI may not consistently convert to higher weight gain throughout the whole life course,” Rukh said. “Instead, according to our observations in two large prospective cohorts, such genetic effects on weight gain seem to be age dependent. Before middle age, greater genetic risk for higher BMI results in a higher risk for weight gain, while after middle age, greater genetic risk or higher BMI results in a lower risk for weight gain.”

For more information:

Rukh G. Abstract #79. Presented at: 50th EASD Annual Meeting; Sept. 16-19, 2014; Vienna.

Disclosure: See the abstract for a complete list the researchers’ relevant financial disclosures.