A Common Genetic Variant Is Associated with Adult and Childhood Obesity

Abstract

Obesity is a heritable trait and a risk factor for many common diseases such as type 2 diabetes, heart disease, and hypertension. We used a dense whole-genome scan of DNA samples from the Framingham Heart Study participants to identify a common genetic variant near the INSIG2 gene associated with obesity. We have replicated the finding in four separate samples composed of individuals of Western European ancestry, African Americans, and children. The obesity-predisposing genotype is present in 10% of individuals. Our study suggests that common genetic polymorphisms are important determinants of obesity.

The single nucleotide polymorphism upstream of insulin-induced gene 2 (INSIG2) is associated with the prevalence of hypercholesterolaemia, but not with obesity, in Japanese American women

“…We could not provide any support for the results reported by Herbert et al that the rs7566605 SNP is associated with obesity, as assessed by BMI in five out of six cohorts (5) . Furthermore, we suggest that other parameters related to obesity, such as waist girth and %fat, were also not influenced by the SNP.…”

“…The relationship between the SNP and the degree of obesity is extremely interesting, because it was suggested that the key factors to resolving the controversy would be the degree of BMI. In short, the SNP is likely to influence BMI in obese subjects rather than lean subjects (5,6) .We hypothesised that the rs7566605 SNP is associated with hypercholesterolaemia or hypertriacylglycerolaemia, since the polymorphism, which is located upstream of INSIG2, may influence the expression of insig-2. Therefore, we investigated the association between the SNP and the prevalence of hypercholesterolaemia or hypertriacylglycerolaemia as well as obesity in Japanese American and Japanese subjects.…”

“…In addition, insig-2-overexpressing mice exhibit lower plasma TAG levels compared with wild-type mice, independent of food intake, body weight and fat weight (4) , which suggests the association between insig-2 and TAG metabolism. Taken together, it is suggested that insig-2 is strongly related to cholesterol and TAG metabolism through the level of insig-2 expression.Recently, an interesting single nucleotide polymorphism (SNP), rs7566605, which is located 10 kb upstream of INSIG2, was found to be associated with obesity, as assessed by BMI (5) . This polymorphism was identified from a genomewide association scan of 86 604 SNP in the Framingham Heart Study offspring cohort.…”

Genetic variations in regulatory pathways of fatty acid and glucose metabolism are associated with obesity phenotypes: a population-based cohort study

“…Genome-wide association studies, a hypothesis-free approach to find genetic areas associated with a trait, identified associations between genetic variations in the INSIG2, FTO, CTNNBL1 and MC4R gene and obesity. 15,[21][22][23] So far, very few studies used a hypothesisdriven pathway-based approach to study many genes from the same pathway in relation to obesity. 24 Nuclear receptors are transcription factors that regulate the expression of target genes through binding to a specific DNA sequence in the target gene, the so-called hormone response element.…”

The pursuit of genome-wide association studies: where are we now?

“…25,26 The identification of the INSIG2 gene for obesity has not been consistently replicated; many studies have been trying to verify the finding, but the association was only found in some but not all the studies. 27 Therefore, a well-conducted meta-analysis is required to resolve the conflicting results.…”