A large international study has identified three new gene variants associated with body mass index (BMI) levels in adults. A consortium of approximately 200 researchers performed a meta-analysis of 46 studies, covering gene data from nearly 109,000 adults spanning four ethnic groups.

By discovering links to lipid-related diseases, type 2 diabetes, and other disorders, the IBC 50K SNP Array BMI Consortium's study may provide fundamental insights into the biology of adult obesity. Scientists from the Center for Applied Genomics led the study by using the Cardiochip, a gene array containing probes for some 50,000 genetic variants across 2,100 genes relevant to cardiovascular and metabolic functions.

"BMI is a widely used measure of obesity, which affects one third of U.S. adults, and approximately half a billion people worldwide," said Children's Hospital's Yiran Guo, PhD, who led the meta-analysis. "Previous studies have shown that genetics plays an important role in obesity, and this study expands our knowledge of BMI genetics."

The researchers first analyzed a dataset of approximately 51,000 individuals of European ancestry (EA) to discover initial gene signals, and then performed replication studies in another 27,000 EA subjects, as well as 14,500 additional EA individuals. Further analyses of data from approximately 12,300 African Americans, 2,600 Hispanics, and 1,100 East Asians strengthened the team's findings.

The consortium uncovered three novel signals, from the genes TOMM40-APOE-APOC1, SREBF2, and NTRK2 that were significantly associated with BMI in adults. All three genes had previously been linked to other important disorders. The team was able to test for conditional associations within genes — independent signals from within the same gene locus, Dr. Guo noted. In particular, the researchers discovered that two genes, BDNF and MC4R, each harbor two independent signals for BMI. Both genes were among eight genes previously associated with BMI that the current study was able to replicate.

"While the individual effects of each gene may be small, they may provide fundamental clues to the biology of adult obesity," Dr. Guo said, adding that further studies will investigate gene-gene interactions for the same trait.

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