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Genetic contribution and pathophysiology of obesity

Authors
George A Bray, MD
Leigh Perreault, MD
Section Editor
F Xavier Pi-Sunyer, MD, MPH
Deputy Editor
Kathryn A Martin, MD

INTRODUCTION

Obesity has many causes, each of which has a variable genetic component [1-4]. At one extreme are the kinds of obesity caused by single-gene mutations. At the other extreme are the kinds of obesity caused by various diseases (such as damage to the ventromedial hypothalamus) in subjects in whom obesity would otherwise not occur [1].

This topic will review the types of obesity caused by single-gene defects, the genetic susceptibility to obesity, and the pathogenetic mechanisms that operate within this genetic framework to cause differences in total body fat content and in regional fat distribution.

Other risk factors associated with the development of obesity, such as diet, lifestyle, drugs, and endocrine disorders, are discussed elsewhere. (See "Obesity in adults: Etiology and natural history".)

HERITABLE FACTORS

Studies of twins, adoptees, and families all suggest the existence of genetic factors in humans with obesity [5,6]. The heritability of obesity estimated from twin studies is high, ranging from 60 to 90 percent, with only slightly lower values in twins raised apart compared with those raised together. Similarly, in adoptees, the body mass index (BMI) correlates with that of their biologic parents rather than that of their adoptive parents.

Common obesity — Obesity is a heritable trait, but the genes that contribute to the more common forms of obesity have been a challenge to identify. A combined meta-analysis of genome-wide association studies (GWAS) (n = 82) and Metabochip studies (n = 43) in nearly 340,000 individuals identified 97 loci associated with BMI [7]. These loci accounted for approximately 2.7 percent of the variation in BMI, and the authors estimated that as much as 21 percent of BMI variation can be accounted for by common genetic variation.

                             

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Literature review current through: Apr 2017. | This topic last updated: May 10, 2017.
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