 By LEE BOWMAN Scripps Howard News Service April 15, 2006
Geneticists have estimated that a person inherits 30 percent to 70 percent of a tendency to be fat or thin (or body mass index) from his or her parents. At least 70 different mutations or variants of 10 different genes have been implicated in obesity thus far, but just how common the mutations are in people or groups of people is not always clear.
An estimated 65 percent of Americans are overweight and 30 percent are considered obese. Obesity is a risk factor for a variety of diseases, including diabetes, stroke and high blood pressure. A new study - which used a pioneering statistical technique to test more than 86,000 DNA sequence variations - has identified yet another gene variant that's linked to BMI, an obesity index based on the ratio of weight to height. And after studying the DNA samples from five different study groups, the researchers calculated that the obesity-predisposing genotype is present in about 10 percent of populations around the world. Such widespread distribution suggests that the variant has been common in humans for a long time. And, like other gene mutations related to fat storage and eating habits, it probably gave a competitive advantage to early humans who lived with the uncertain food supplies associated with hunting and gathering, only becoming a liability with the abundant food supplies of modern times. The study, published Friday in the journal Science, started with blood samples taken from nearly 700 participants in the landmark Framingham Heart Study, which has tracked heart disease through three generations of residents of the Massachusetts town since 1948. Normally, a search for one gene variant most tied to obesity out of a field of tens of thousands would use a two-step process that first selected a smaller group of candidates, then a second round of screening. But using a technique developed by the Harvard School of Public Health that estimated the extent that genetics can explain variations in a specific trait, the researchers found a single candidate. The variant lies near an insulin-induced gene (INSIG2) that's known to produce a protein that controls the burn rate of fatty acid and cholesterol. "Although these variants are likely to carry low relative risk, their impact on health is substantial because of their (widespread) prevalence in the population," wrote the team led by Alan Herbert, a professor at Boston University School of Medicine. With the new obesity culprit in hand, the researchers joined with scientists at other institutions to determine if the variant could also be linked to an increased risk of obesity in other groups. Those studies confirmed the same association in four of five independent groups, including those of Western European ancestry, blacks and children, and which included both families and unrelated subjects. The analysis also confirmed that people had to have inherited two copies of the mutation to face the increased risk of obesity. The link did not hold up in one study group, a sample from the Nurses Health Study at Harvard University that was involved in research on diabetes and breast cancer. The researchers noted that there were fewer individuals with high BMI compared to those in the other study groups, and that this different distribution of weight or differences in environment or lifestyle among the nurses may have affected the result. "Several features make this study especially exciting: the large-scale genotyping (screening), the use of population samples of families, the long-term follow-up of the subjects, the replication of the finding in independent samples and novel statistical methodology," said Nan Laird, a professor at Harvard and co-author of the paper. She explained that most genetic studies of obesity have involved unrelated subjects who were not monitored for physical characteristics over time, making replication of the results more difficult.
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