The genetics of obesity and the metabolic syndrome

Abstract

In this review, we discuss the genetic architecture of obesity and the metabolic syndrome, highlighting recent advances in identifying genetic variants and loci responsible for a portion of the variation in components of the metabolic syndrome, namely, adiposity traits, serum HDL and triglycerides, blood pressure, and glycemic traits. We focus particularly on recent progress from large-scale genome-wide association studies (GWAS), by detailing their successes and how lessons learned can pave the way for future discovery. Results from recent GWAS coalesce with earlier work suggesting numerous interconnections between obesity and the metabolic syndrome, developed through several potentially pleiotropic effects. We detail recent work by way of a case study on the cadherin 13 gene and its relation with adiponectin in the HyperGEN and the Framingham Heart Studies, and its association with obesity and the metabolic syndrome. We provide also a gene network analysis of recent variants related to obesity and metabolic syndrome discovered through genome-wide association studies, and 4 gene networks based on searching the NCBI database.

Figure 1

A network of genes that includes 17 interactions with Cadherin 13 gene (CDH13), comprising Adiponectin. Highlighted in yellow are direct interactions with CDH13. (The network is built using the curated literature of GeneGO Inc.)

Figure 2

Association tests results expressed as negative log10 p-value (> 1.3) of a number of SNPs selected from a region on chromosome 16, starting at 82MBs–84MBs, which comprises CDH13. The association tests were implemented with latent factors result of factor analysis on a number of risk variables for obesity and metabolic syndrome (see text).

Figure 3

A network of genes or intragenic SNPs reported from the most recent GWAS in relation to obesity and metabolic syndrome. Results represented here include those that attempted to assay at least 100,000 SNPs in the initial stage, and are limited to those with p-values <1.0×10⁻⁵. (Source: http://www.genome.gov/gwastudies/, accessed on April 05, 2010).