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Genetic markers

Analysis finds new genetic loci for obesity

Researchers found new genetic loci associated with obesity, as well as confirming those found in previous studies. Photo: Flickr / Net_Efekt
Associations identified between gene variations and adult BMI
Study involved genetic data from more than 100,000 adults

A meta-analysis of 46 genetic studies has identified three gene variants associated with increased BMI levels in adults. The analysis, which included genetic data from 108,912 adults, found links between genes associated with other conditions, including type 2 diabetes and Alzheimer’s disease, helping to illustrate the contribution of genetics to adult obesity.

The new genetic signals identified by The study, which was performed by a consortium of more than 200 researchers, may lay the groundwork for insights into the biology of human obesity, and its links to lipid-related disorders.

Lead author Yiran Guo, of Children’s Hospital of Philadelphia, said that “while the individual effects of each gene may be small, they may provide fundamental clues to the biology of adult obesity.”

Methodology

The study used a gene array comprising of probes for 49,320 genetic variants across around 2,100 metabolic and cardiovascular-related loci.

The researchers uncovered three novel signals, from the genes TOMM40-APOE-APOC1, SREBF2 and NTRK2, that were significantly associated with BMI in adults. All had previously been linked to other important disorders.

A meta-analysis of studies involving around 51,000 individuals of European ancestry revealed some initial gene signals, which were replicated in studies of another 27,000 individuals.

Further analysis of data from around 12,300 African Americans, 2,600 Hispanics and 1,100 East Asians strengthened the findings.

The APOE locus is well known to be involved in blood lipid regulation and circulation, and plays an important role in Alzheimer's disease. The SREBF2 gene is in the same family as SREBF1, linked to type 2 diabetes in another study using the same array. Finally, NTRK2 codes for a receptor of the BDNF protein, which is known to be related to BMI and is associated with anorexia.

Guo also noted that the team was able to test for conditional associations within genes -- independent signals from within the same gene locus.

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, including FTO, SH2B1 and COL4A3BP-HMGCR.

As well as finding the new gene signals, the study was able to replicate evidence from previous studies associating ten genetic loci on the array with adult BMI. Out of 10 genetic loci identified in previous studies, the analysis replicated eight, with the remaining two showing nominal significance.

"Previous studies have shown that genetics plays an important role in obesity, and this study expands our knowledge of BMI genetics,” said Guo.

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