Sugar-sweetened beverages and genetic risk of obesity

Abstract

Background: Temporal increases in the consumption of sugar-sweetened beverages have paralleled the rise in obesity prevalence, but whether the intake of such beverages interacts with the genetic predisposition to adiposity is unknown.

Methods: We analyzed the interaction between genetic predisposition and the intake of sugar-sweetened beverages in relation to body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) and obesity risk in 6934 women from the Nurses' Health Study (NHS) and in 4423 men from the Health Professionals Follow-up Study (HPFS) and also in a replication cohort of 21,740 women from the Women's Genome Health Study (WGHS). The genetic-predisposition score was calculated on the basis of 32 BMI-associated loci. The intake of sugar-sweetened beverages was examined prospectively in relation to BMI.

Results: In the NHS and HPFS cohorts, the genetic association with BMI was stronger among participants with higher intake of sugar-sweetened beverages than among those with lower intake. In the combined cohorts, the increases in BMI per increment of 10 risk alleles were 1.00 for an intake of less than one serving per month, 1.12 for one to four servings per month, 1.38 for two to six servings per week, and 1.78 for one or more servings per day (P<0.001 for interaction). For the same categories of intake, the relative risks of incident obesity per increment of 10 risk alleles were 1.19 (95% confidence interval [CI], 0.90 to 1.59), 1.67 (95% CI, 1.28 to 2.16), 1.58 (95% CI, 1.01 to 2.47), and 5.06 (95% CI, 1.66 to 15.5) (P=0.02 for interaction). In the WGHS cohort, the increases in BMI per increment of 10 risk alleles were 1.39, 1.64, 1.90, and 2.53 across the four categories of intake (P=0.001 for interaction); the relative risks for incident obesity were 1.40 (95% CI, 1.19 to 1.64), 1.50 (95% CI, 1.16 to 1.93), 1.54 (95% CI, 1.21 to 1.94), and 3.16 (95% CI, 2.03 to 4.92), respectively (P=0.007 for interaction).

Conclusions: The genetic association with adiposity appeared to be more pronounced with greater intake of sugar-sweetened beverages. (Funded by the National Institutes of Health and others.).

Figure 1. Relative Risk of the Development of Obesity per Increment of 10 Risk Alleles, According to Intake of Sugar-Sweetened Beverages

For the discovery phase, with data from the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts, the analyses were based on 18 years of follow-up for 6402 initially nonobese women (1980 to 1998, 1107 incident cases of obesity) and 12 years of follow-up for 3889 initially nonobese men (1986 to 1998, 297 incident cases of obesity). Shown are the pooled relative risks of incident obesity, with adjustment for age, source of genotyping data, level of physical activity, status with respect to current smoking, alcohol intake, time spent watching television, Alternative Healthy Eating Index score, and total energy intake. For the replication phase, with data from the Women’s Genome Health Study (WGHS) cohort, the analyses were based on a median of 6 years of follow-up for 18,127 initially nonobese women (1992 to 1998, 2280 incident cases of obesity). Shown are the relative risks of incident obesity, with adjustment for age, geographic region, eigenvectors, level of physical activity, status with respect to current smoking, alcohol intake, and total energy intake. Horizontal bars indicate 95% confidence intervals.

Figure 2. Difference in BMI Associated with One Serving of a Sugar-Sweetened Beverage per Day, According to the Quartile of the Genetic-Predisposition Score

Data are effect sizes (β coefficients [±SE]) of sugar-sweetened beverage intake (one serving per day) on body-mass index (BMI; the weight in kilograms divided by the square of the height in meters), stratified according to the quartile of the genetic-predisposition score. In the NHS cohort, the median scores across the quartiles were 24.5 (range, 13.1 to 26.3), 27.8 (range, 26.4 to 29.0), 30.3 (range, 29.1 to 31.7), and 33.6 (range, 31.8 to 43.4); in the HPFS cohort, 24.9 (range, 16.0 to 26.5), 27.9 (range, 26.6 to 29.1), 30.4 (range, 29.2 to 31.7), and 33.6 (range, 31.8 to 41.9); and in the WGHS cohort, 24.7 (range, 15.3 to 26.5), 27.8 (range, 26.6 to 29.1), 30.3 (range, 29.2 to 31.6), and 33.4 (range, 31.7 to 43.4). In the NHS and HPFS cohorts, the analyses were based on data from the first 4 years in women (1980 to 1984) and men (1986 to 1990), respectively, with adjustment for age, source of genotyping data, level of physical activity, time spent watching television, status with respect to current smoking, alcohol intake, and Alternative Healthy Eating Index score. In the WGHS cohort, the analyses were based on data from the first 3 years, with adjustment for age, geographic region, eigenvectors, level of physical activity, status with respect to current smoking, and alcohol intake. P values are for interaction. I bars indicate standard errors.