Largest Ever Genome-Wide Study Strengthens Genetic Link to Obesity

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Newswise ANN ARBOR, Mich. There are many reasons why people gain different amounts of weight and why fat becomes stored in different parts of their bodies. Now researchers are homing in on genetic reasons. Their findings, part of the largest genome-wide study to date, were published in two companion papers today in the journal Nature.

By analyzing genetic samples from more than 300,000 individuals to study obesity and body fat distribution, researchers in the international Genetic Investigation of Anthropometric Traits (GIANT) Consortium completed the largest study of genetic variation to date, and found over 140 locations across the genome that play roles in various obesity traits.

By applying novel computational methods to the genetic results, they discovered new biological pathways that are important in controlling body weight and fat distribution.

This work is the first step toward finding individual genes that play key roles in body shape and size. The proteins these genes help produce could become targets for future drug development.

Obesity is a global public health burden that affects millions of people. Yet, there are no long-term treatments.

Waist-to-hip ratios key for health risk One paper focused on where fat is stored in the body, one determinant of health risk. One of the observable traits linked to the genetic locations was waist-to-hip circumference ratio. People with waistlines larger than hip circumferences have more belly fat surrounding their abdominal organs. This makes them more likely to have metabolic conditions, such as type-2 diabetes, and cardiovascular problems than do people with body fat concentrated more in the hip area or distributed equally throughout the body.

We need to know these genetic locations because different fat depots pose different health risks, says Karen Mohlke, Ph.D., professor of genetics at the University of North Carolina School of Medicine and senior author of the paper that examined waist-to-hip ratio of fat distribution. If we can figure out which genes influence where fat is deposited, it could help us understand the biology that leads to various health conditions, such as insulin resistance/diabetes, metabolic syndrome, and heart disease.

The genetic locations associated with fat depots are associated with genes previously identified as being important for the creation of adipose tissue. Researchers also determined that 19 of the fat distribution genetic locations had a stronger effect in women; one had a stronger effect in men.

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Largest Ever Genome-Wide Study Strengthens Genetic Link to Obesity