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Small genetic change carries a lot of weight

U. QUEENSLAND (AUS) —Even a small change to the DNA sequence can have a significant effect on body mass index, a new study shows.

Body mass index or BMI measures someone’s weight adjusted for height.

Published in the journal Nature, the research focuses on a single change in genetic sequence at the gene FTO.  The genetic change, called a single nucleotide polymorphism (SNP), was the replacement of one nucleotide—the units that make up our DNA—with another, says Peter Visscher, professor of quantitative genetics at the University of Queensland.

“They are the most abundant type of variation in the human genome. SNPs occur normally throughout our DNA and most have no effect on our health, however, we’ve found one that does have a small but significant effect on variation in BMI.”


After analyzing data from almost 170,000 people, Visscher and colleagues established that those with a sequence variant in the FTO gene not only weighed more on average, but the measured weights varied more than in the group without the variant.

The variability of BMI within the group with two copies of the variant was, in fact, seven percent larger than the group without the variant. This equates to around half a kilogram difference in the standard deviation of weight.

“So as a group, people with two copies of the weight increasing variant are a few kilograms heavier and vary more,” he says.

Genetic differences in variability of specific traits have been seen in many plant and animal species but specific genes or mechanisms to explain the phenomenon had not been identified.

Visscher’s study is the first to look systematically at genetic effects on variation of a complex trait in humans using a very large sample size. “The study is important because it demonstrates that genes can be found that affect trait variability. This is a first step towards understanding how genes control variation.”

The study is also the first to offer researchers an indirect method to measure genotype by environment interactions without having a measure of specific environmental factors.

“If a gene interacts with specific environmental factors then this can be observed with our method. For example, if the effect of a gene on weight is smaller in people who physically exercise than in people who do not, then this will lead to less variation among people with two copies of the weight decreasing variant.

“In our study we did not measure specific environmental effects such as physical exercise so we can’t say for sure whether our results are due to a genotype-environment interaction.”

Source: University of Queensland

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