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special/viewpoint: Kathleen Ries Merikangas and Neil Risch Genomic Priorities and Public Health Science 2003; 302: 599-601 [Abstract] [Full text] [PDF]

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Complex diseases influenced by environmental risk factors may require complex cures.

Craig H. Warden, Janis S. Fisler   (20 November 2003)

Complex diseases influenced by environmental risk factors may require complex cures. 20 November 2003
Craig H. Warden, Geneticist UC Davis, Janis S. Fisler Respond to this E-Letter: Re: Complex diseases influenced by environmental risk factors may require complex cures.	Merikangas and Risch (1) argue that complex diseases should be prioritized for genetic research based on several criteria including whether or not there is a “limited ability to modify exposure or risk factors.” Based on their criterion, genetic studies of type 2 diabetes, which they suggest appears “to be highly amenable to environmental modification," i.e. prevention of obesity and physical inactivity, would have lower priority for funding. Although there have been positive reports that intensive diet and exercise interventions reduce the incidence of type2 diabetes (2), these studies have not demonstrated that lifestyle interventions have lifetime effects, or that they prevent diabetes in all subjects, or that these treatments are effective for the most obese patients. Despite the annual expenditure of more than $33 billion (1995 dollars) per year on weight reduction products and services (3), most patients who complete weight loss programs lose only about 10% of their body weight, regain two-thirds back within one year, and most of it back within five years (3). Indeed, the obesity epidemic has grown in magnitude such that now more than half of the U.S. population is overweight or obese. The lack of efficacy of currently available therapies for obesity has driven many seriously obese individuals to choose gastric bypass surgery. An estimated 120,000 Americans this year will opt for this radical treatment, and many more will make the same choice unless fundamentally different approaches are developed for obesity treatment. It is clear that genetics influences many aspects of obesity, from response to diet and exercise, to maternal effects and major gene effects. Finding the underlying genes offers at least the possibility that novel therapeutic targets may be discovered for the prevention of obesity and its sequellae: type 2 diabetes, cardiovascular disease, and cancer. 1. K. R. Merikangas, N. Risch, Science 302, 599 (2003). 2. W. C. Knowler et al., N. Engl. J. Med. 346, 393 (2002). 3. Committee to Develop Criteria for Evaluation the Outcomes of Approaches to Prevent and Treat Obesity. P. R. Thomas, Ed., Food and Nutrition Board (Institute of Medicine, National Academy Press, Washington, D.C., 1995).