Book Review

Obesity: Genomics and Postgenomics

N Engl J Med 2008; 358:2417-2418May 29, 2008

Article

Obesity: Genomics and Postgenomics
Edited by Karine Clément and Thorkild I.A. Sørensen. 576 pp., illustrated. New York, Informa Healthcare, 2008. $249.95. ISBN: 978-0-8493-8089-1

Now is the perfect time for a book about obesity and genomics. The prevalence of obesity is increasing worldwide, and about two thirds of the population of the United States is obese or overweight. The fields of genetics, genomics, and pharmacogenomics are progressing rapidly and are prominent in both the lay press and scientific journals.

We can gain perspective on how far we have come in the field of obesity genetics by considering that William Osler wrote in 1892 that “the tendency to polysarcia or obesity is often hereditary.” By the 1920s, reports of familial aggregation of obesity had started to appear in the medical literature. The hereditary nature of human obesity was firmly established later by twin studies. The first animal model of monogenic obesity, the viable yellow mouse, was reported in 1905. However, it was not until 1994 that the first mechanistic elucidation of a monogenic cause of murine obesity, leptin deficiency, was reported. Leptin deficiency was also the first monogenic cause of human obesity that was identified, 3 years later.

During the past two decades, the predominant approaches to studying the genetics of human obesity have been linkage and candidate-gene studies. We now believe that many genes (hundreds, maybe thousands) can contribute to the regulation of body weight. Obesity genetics is on the cusp of a new era. The first obesity locus to be identified in a genomewide association study was FTO in 2007; the identification of many more such loci will presumably follow. Information gained in the study of obesity genetics by such powerful new tools cannot stand alone, however, but must be applied to our understanding of the physiology of energy homeostasis and the biology of obesity, and then to the treatment of obesity and its coexisting conditions.

Two Mice with a Defect in a Gene Called Obese (ob).

Obesity reviews the history, evolution, and future directions of obesity research. The editors have divided the book into 11 sections, but the chapters can also be divided into three basic categories. The first category includes established fields, such as the classic family and twin studies that clearly demonstrated the existence of a genetic component to obesity. These chapters contain excellent discussions of the reported data as well as some new summaries. The chapters on the monogenic causes of obesity in mice and humans provide comprehensive discussions of our current understanding of the biology of obesity. The material covered by these chapters is unlikely to change rapidly, making these sections a useful resource for years to come.

The chapters in the second category summarize linkage and candidate-gene studies and provide a good overview of current knowledge in these areas. The summaries are timely and valuable, but the information is likely to be modified in the near future, particularly as replication studies in independent cohorts are emphasized. The findings from candidate-gene studies will also need to be integrated with results from genomewide association studies.

The chapters in the third category concern topics that have not yet been definitively tied to obesity in a mechanistic way (e.g., epigenetics). The inclusion of these chapters is understandable given the potential importance of these areas. However, with the current absence of data on how these topics apply to obesity, recent journal reviews may provide the most up-to-date reading.

One minor issue with the book is its subtitle. At this time, the term “postgenomics” means different things to different researchers, and one might look to current journals for the latest approach to the integration of systems biology into obesity genetics and genomics. Overall, this is a timely publication that will serve as a useful reference in the broad and growing field of obesity research.

Steven B. Heymsfield, M.D.
Marc L. Reitman, M.D., Ph.D.
Merck Research Laboratories, Rahway, NJ 07065
steven_heymsfield@merck.com