Genetic studies of common types of obesity: a critique of the current use of phenotypes

Abstract

Recent research into the genetic basis of obesity has focused upon the study of candidate genes, both functional and positional, of genes underlying weight-related Mendelian disorders and of susceptibility loci identified in genome-wide association studies. Three large genome-wide association studies on obesity, together involving more than 150,000 individuals, were published in Nature Genetics last year. The results suggested the involvement of a large number of genetic variants in disease susceptibility. Most genetic effects upon body weight are likely to become obscured by the use of inappropriate phenotypes. In particular, clinical categories such as the body mass index and Metabolic Syndrome do not provide sufficient etiological information for them to be used sensibly in genetic studies on obesity or obesity-related disease. Alleviation of this situation will not come from new genomic research tools, sophisticated statistical algorithms or ever larger sample sizes. Instead, the above notions argue in favour of so-called 'deep phenotyping'.