The genetics of obesity: from discovery to biology

The prevalence of obesity has tripled over the past four decades, imposing an enormous burden on people’s health. Polygenic (or common) obesity and rare, severe, early-onset monogenic obesity are often polarized as distinct diseases. However, gene discovery studies for both forms of obesity show tha...

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Published in:Nature reviews. Genetics Vol. 23; no. 2; pp. 120 - 133
Main Authors: Loos, Ruth J. F., Yeo, Giles S. H.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.02.2022
Nature Publishing Group
Subjects:
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Age
Agriculture
Animal Genetics and Genomics
Animals
Biomedical and Life Sciences
Biomedicine
Body weight
Cancer Research
Eating - genetics
Gene Function
Gene-Environment Interaction
Genetic Predisposition to Disease - genetics
Genetic Variation
Genome, Human - genetics
Genome-wide association studies
Genome-Wide Association Study - methods
Genomes
Human Genetics
Humans
Multifactorial Inheritance - genetics
Obesity
Obesity - genetics
Overweight - genetics
Review
Review Article
Whole Genome Sequencing - methods
ISSN:1471-0056, 1471-0064, 1471-0064
Online Access:Get full text
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Summary:The prevalence of obesity has tripled over the past four decades, imposing an enormous burden on people’s health. Polygenic (or common) obesity and rare, severe, early-onset monogenic obesity are often polarized as distinct diseases. However, gene discovery studies for both forms of obesity show that they have shared genetic and biological underpinnings, pointing to a key role for the brain in the control of body weight. Genome-wide association studies (GWAS) with increasing sample sizes and advances in sequencing technology are the main drivers behind a recent flurry of new discoveries. However, it is the post-GWAS, cross-disciplinary collaborations, which combine new omics technologies and analytical approaches, that have started to facilitate translation of genetic loci into meaningful biology and new avenues for treatment. In this Review, Loos and Yeo summarize our current understanding of the genetic underpinnings of monogenic and polygenic obesity. They highlight the commonalities revealed by recent studies and discuss the implications for treatment and prediction of obesity risk.
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ISSN:1471-0056
1471-0064
1471-0064
DOI:10.1038/s41576-021-00414-z