Erratum: Functional Analysis of Seven Genes Linked to Body Mass Index and Adiposity by Genome-Wide Association Studies: A Review
2017-07-25T13:44:42Z (GMT) by
Genome-wide association studies (GWAS) have identified a total of about 40 single nucleotide polymorphisms (SNPs) that show significant linkage to body mass index, a widely utilised surrogate measure of adiposity. However, only 8 of these associations have been confirmed by follow-up GWAS using more sophisticated measures of adiposity (computed tomography). Among these 8, there is a SNP close to the gene <i>FTO</i> which has been the subject of considerable work to diagnose its function. The remaining 7 SNPs are adjacent to, or within, the genes <i>NEGR1, TMEM18, ETV5, FLJ35779, LINGO2, SH2B1</i> and <i>GIPR</i>, most of which are less well studied than <i>FTO,</i> particularly in the context of obesity. This article reviews the available data on the functions of these genes, including information gleaned from studies in humans and animal models. At present, we have virtually no information on the putative mechanism associating the genes <i>FLJ35779</i> and <i>LINGO2</i> to obesity. All of these genes are expressed in the brain, and for 2 of them <i>(SH2B1</i> and <i>GIPR)</i>, a direct link to the appetite regulation system is known.<i> SH2B1</i> is an enhancer of intracellular signalling in the JAK-STAT pathway, and <i>GIPR </i>is the receptor for an appetite-linked hormone (GIP) produced by the alimentary tract. <i>NEGR1, ETV5</i> and <i>SH2B1</i> all have suggested roles in neurite outgrowth, and hence SNPs adjacent to these genes may affect development of the energy balance circuitry. Although the genes have central patterns of gene expression, implying a central neuronal connection to energy balance, for at least 4 of them <i>(NEGR1, TMEM18, SH2B1</i> and <i>GIPR)</i>, there are also significant peripheral functions related to adipose tissue biology. These functions may contribute to their effects on the obese phenotype.