As obesity becomes an increasingly prominent health condition in the United States, University researchers have made new discoveries about the biological pathways that cause it.

In the largest genome-wide study ever, the Genetic Investigation of Anthropometric Traits consortium of researchers analyzed more than 300,000 genetic samples and found 97 new genetic locations across the genome that are associated with obesity and body mass index — triple the number of previously known sites.

This finding led researchers to believe obesity is much more related to one’s genes than was previously thought.

Elizabeth Speliotes, assistant professor of internal medicine and a senior author of the GIANT study, said if scientists can pinpoint the specific gene variants or proteins that contribute to obesity, then therapeutic interventions can directly target them.

Speliotes said the study could lead to a new era of “tailored” obesity care.

“We are realizing that many of the common diseases we aim to treat are caused by multiple different underlying causes,” Speliotes said. “So now we can understand what those causes are and better define them. And then hopefully in the future we can sub-classify people into what they are at risk for versus what the general population is at risk for.”

Currently, therapeutic interventions are often generalized to diseases. For example, the same medications are often prescribed to all patients suffering from the same disease. Outcomes from these interventions have not been very successful.

“Right now we don’t know what the exact causes are for different diseases, so a lot of the stuff we do is like shooting in the dark,” Speliotes said.

In a companion study, an international consortium of researchers led by Karen Mohlke, professor of genetics at the University of North Carolina School of Medicine, identified 49 sites in the human genome associated with the human waist-to-hip ratio.

Mohlke said the waist-to-hip ratio is often associated with obesity because most people with waistlines larger than their hip circumference have more visceral fat around their abdominal organs, making them susceptible to diseases such as type 2 diabetes and cardiovascular diseases.

Identifying specific gene sites associated with the waist-to-hip metric has implications for tailoring and personalizing treatments to individual patients. The study also found men and women vary in their genetic makeup with regard to the waist-to-hip ratio.

“Many of the associations between the genetic variants and waist-to-hip ratios that we identified have stronger effects in women than in men,” Mohlke said.

Specifically, 19 of the waist-to-hip genetic locations identified had a stronger effect in women. Only one had a stronger effect in men.

The use of large data sets and innovative data algorithms was crucial to both studies. Larger sample sizes, which were made possible by collaboration between research institutions from all over the world, ensured that enough data would be available for the true signal to be differentiated from the statistical noise, Speliotes said.

Speliotes added that a greater understanding of each individual’s specific genotype has excited researchers across the board. Knowing each individual’s particular genetic susceptibilities and advantages would allow physicians to give therapy to each patient that is not necessarily right for their neighbor, but that is right for them.

“A lot of medicine is going in a personalized direction,” she said.

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