Association studies of genetic polymorphisms in central obesity: a critical review

During the past decade, mutations affecting liability to central obesity have been discovered at a phenomenal rate, and despite few consistently replicated findings, a number of intriguing results have emerged in the literature. Association studies have been proposed to identify the genetic determinants of complex traits such as central obesity. The advantages of the association method include its relative robustness to genetic heterogeneity and the ability to detect much smaller effect sizes than is detectable using feasible sample sizes in linkage studies. However, the current literature linking central obesity to genetic variants is teeming with reports of associations that either cannot be replicated or for which corroboration by linkage has been impossible to find. Explanations for this lack of reproducibility are well rehearsed, and typically include poor study design, incorrect assumptions about the underlying genetic architecture, and simple overinterpretation of data. These limitations create concern about the validity of association studies and cause problems in establishing robust criteria for undertaking association studies. In this article, the current status of the literature of association studies for genetic dissection of central obesity is critically reviewed.