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Genetic Obesity Risk Heightened by Sugary Drinks

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SAN ANTONIO -- The relationship between genetics, body mass index, and obesity risk appears to be magnified in adults who drink the most sugar-sweetened beverages, researchers found.

A genetic predisposition score that included a collection of 32 previously identified single-nucleotide polymorphisms was significantly associated with BMI across levels of sugar-sweetened beverage intake, according to Lu Qi, MD, PhD, of the Harvard School of Public Health in Boston.

Action Points

  • This study showed that in two cohorts, increases in body mass index (BMI) and the relative risk of incident obesity were associated with genetic predisposition and the number of risk alleles.
  • Note, however, that the genetic association with adiposity was more pronounced the greater the intake of sugar-sweetened beverages.

However, the average increase in BMI associated with each increment of 10 risk alleles rose from 1.00 kg/m2 in individuals drinking less than one serving of sugary drinks per month to 1.78 kg/m2 for those drinking at least one serving per day, he reported at the Obesity Society meeting here. The findings were reported simultaneously online in the New England Journal of Medicine.

"These data suggest that persons with greater consumption of sugar-sweetened beverages may be more susceptible to genetic effects on adiposity," the researchers wrote.

"Viewed differently, persons with a greater genetic predisposition to obesity appeared to be more susceptible to the deleterious effects of sugar-sweetened beverages on BMI," they continued. "Our findings underscore the need to test interventions that reduce the intake of sugary drinks as a means of reducing the risk of obesity and related diseases."

Two such interventions were reported at the meeting and published in NEJM, both of which provided some evidence that reducing the intake of sugary drinks slowed increases in body mass index in children and teens. One of those trials, however, showed a benefit only on secondary endpoints.

"Although further evidence is warranted," Qi and colleagues wrote, "these data support a causal relationship among the consumption of sugar-sweetened beverages, weight gain, and the risk of obesity."

In comments emailed to ѻý and ABC News, Barbara Moore, PhD, president and CEO of Shape Up America, a nonprofit organization providing information on healthy weight management, added, "These findings and other relevant data suggest that cutting back on sugar-sweetened beverages is likely to be a useful weight management strategy because it is easy, and there is no downside risk because such beverages are not nutritionally valuable."

The researchers explored the issue using data on 6,934 women from the Nurses' Health Study (NHS) -- which included female registered nurses ages 30 to 50 at baseline -- and 4,423 men from the Health Professionals Follow-up Study (HPFS) -- which included men ages 40 to 75 at baseline. Participants in both studies completed food-frequency questionnaires every 4 years.

The findings from those two cohorts were then validated using data on 21,740 women with self-reported European ancestry from the Women's Genome Health Study (WGHS), which included health professionals who were 45 or older and did not have any major chronic diseases at baseline.

The researchers calculated a genetic predisposition score using 32 single-nucleotide polymorphisms that have been correlated with BMI previously in genome-wide association studies.

At baseline, mean intake of sugar-sweetened beverages was relatively low, at 0.33, 0.32, and 0.26 servings per day in the NHS, HPFS, and WGHS cohorts, respectively. Baseline consumption was associated with BMI in all three studies.

In addition, a higher genetic predisposition score was associated with greater BMI in all three cohorts (P<0.001 for all).

In the NHS and HPFS, that relationship was stronger among those who drank more sugar-sweetened beverages. When combining the men and women together, the increases in BMI associated with each increment of 10 risk alleles were 1.00 kg/m2 for those drinking less than one serving per month, 1.12 kg/m2 for one to four servings per month, 1.38 kg/m2 for two to six servings per week, and 1.78 kg/m2 for one or more servings per day (P<0.001 for the interaction).

For those same categories of consumption, the relative risks of developing obesity during follow-up per increment of 10 risk alleles were 1.19 (95% 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 15.50).

Similar trends for BMI and obesity risk were confirmed in the WGHS cohort.

No such trends, however, were observed in relation to consumption of artificially sweetened beverages in any of the cohorts.

"This study provides strong evidence that there is a significant interaction between an important dietary factor – intake of sugar-sweetened beverages – and a genetic-predisposition score, obesity, and the risk of obesity," Sonia Caprio, MD, of Yale University, wrote in an editorial accompanying the NEJM paper.

"Hence," she wrote, "participants with a greater genetic predisposition may be more susceptible to the adverse effects of sugar-sweetened beverages on obesity; this is a clear example of gene-environment interaction."

She noted that the possible mechanisms underlying the findings were not identified in the study, but said that the findings support the need to study whether interventions aimed at reducing the intake of sugary drinks would be more effective at reducing the risk of obesity in populations with a high genetic predisposition to obesity.

In emailed comments to ѻý and ABC News, Keith-Thomas Ayoob, EdD, RD, of Albert Einstein College of Medicine, said that "I wouldn't want people to think that because of a genetic predisposition that can occur to an unknown degree, that weight gain is a 'done deal.' We need to recognize the traps for how we get extra calories. We also need to move more and eat smarter."

Qi and colleagues acknowledged some limitations of the study, including possible measurement errors in consumption of sugary drinks and other aspects of the diet, possible residual confounding, and the use of cohorts predominantly made up of individuals with European ancestry.

This article was developed in collaboration with ABC News.

Disclosures

The study was supported by grants from the NIH, with additional support for genotyping from Merck Research Laboratories, an American Heart Association Scientist Development Award, a Research to Prevent Blindness award, and a Harvard Ophthalmology Scholar Award from the Harvard Glaucoma Center of Excellence. The Women's Genome Health Study is supported by grants from the NIH, with collaborative scientific support and funding for genotyping provided by Amgen.

Qi reported receiving lecture fees from Kellogg. His co-authors reported relationships with Genzyme, Isis Pharmaceuticals, Vascular Biogenics, Merck, Abbott, Novartis, AstraZeneca, Novo Nordisk, and the California Walnut Commission. One of the study authors is listed as a co-inventor on patents held by his institution that relate to the use of inflammatory biomarkers in cardiovascular disease and diabetes (patent and royalty payments are received by Brigham and Women's Hospital.

Caprio reported that she had no conflicts of interest.

Primary Source

New England Journal of Medicine

Qi Q, et al "Sugar-sweetened beverages and genetic risk of obesity" N Engl J Med 2012; DOI: 10.1056/NEJMoa1203039.

Secondary Source

New England Journal of Medicine

Caprio S "Calories from soft drinks -- do they matter?" N Engl J Med 2012; DOI: 10.1056/NEJMe1209884.