Do allelic variants of SLC6A14 predispose to obesity?

Abstract

Obesity is arguably the world's most prevalent nutritional disorder and is a substantial contributor to morbidity and early mortality. Obesity is known to have a strong genetic component, but the specific influential genes in humans are largely unknown. A new paper describes a genetic variant that appears as though it may cause some people to be fatter or thinner than others (see the related article beginning on page 1762). This commentary considers the strength of the evidence in support of this finding and discusses additional research questions that should be addressed in further evaluations of this genetic variant as a putative contributor to human obesity.

Figure 1

Dr. E. Brown, the Largest Man in America. — From a Portrait by Mr. J.R. Dix. Image courtesy of the U.S. National Library of Medicine.

Figure 2

Schematic presentation of the positional cloning strategy. The initial genome-wide linkage scan is followed by fine mapping with additional microsatellite and single SNP markers. Genes showing significant associations with the SNPs are resequenced to identify relevant DNA sequence variants in the study population. The relevance of these mutations is verified with additional association studies in other populations (replications) and using in vitro and in vivo functional studies. Modified with permission from Circulation (22). LOD, log (base 10) of the odds ratio.