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Genome Scan Pinpoints Common Obesity Factor

 Genome analysis of data from the Framingham Heart Study has revealed a common genetic variant that increases the risk of obesity, a team of scientists reported today.

Writing in this week’s issue of Science magazine, researchers and physicians from Boston and their German collaborators have identified a single nucleotide polymorphism (SNP) that lies 10,000 bases upstream of the INSIG2 gene (insulin-induced gene).

Remarkably, the variant is present in 10 percent of the population, and while the researchers acknowledge that it may not be a major risk factor, its prevalence makes it a significant one.

Using the Affymetrix 100K array, the research team, led by Boston University Medical School’s Alan Herbert and Michael Christman, screened more than 116,000 SNPs in 694 participants from the Framingham Heart Study. Using a family-based association test (FBAT), and making certain assumptions about the mode of genetic inheritance, the researchers found only one SNP that was significantly associated with body mass index, or BMI.

The rs7655505 SNP can be a C or a G. Further study showed that individuals with two copies of C at this position are about 1 BMI unit heavier than those with GC or GG. This effect was confirmed in a sample of nearly 4,000 Germans, as well as several other Caucasian populations.

The researchers also examined more than 1200 individuals of African-American descent, adding further confirmation to the findings. The prevalence of the rs7655505 SNP in different populations prompts the authors to conclude that the “risk allele predates human migration out of Africa,” but that it has “only become deleterious in modern times.”

The authors also argue that INSIG2 is “an attractive candidate gene for the quantitative trait locus affecting BMI as it… inhibits fatty acid and cholesterol synthesis.”

Herbert et al. suggest that many such common variants affecting obesity risk are still to be identified. Genome scans using denser microarrays would be one way of increasing the chances that they will.

Featured Report:

Herbert A. et al. “A common genetic variant 10 kb upstream of INSIG2 is associated with adult and childhood obesity.” Science 14 April, 2005.


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