The Association of a SNP Upstream of INSIG2 with Body Mass Index is Reproduced in Several but Not All Cohorts
نویسندگان
چکیده
A SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI) by Herbert and colleagues. The association between increased BMI and homozygosity for the minor allele was first observed in data from a genome-wide association scan of 86,604 SNPs in 923 related individuals from the Framingham Heart Study offspring cohort. The association was reproduced in four additional cohorts, but was not seen in a fifth cohort. To further assess the general reproducibility of this association, we genotyped rs7566605 in nine large cohorts from eight populations across multiple ethnicities (total n = 16,969). We tested this variant for association with BMI in each sample under a recessive model using family-based, population-based, and case-control designs. We observed a significant (p < 0.05) association in five cohorts but saw no association in three other cohorts. There was variability in the strength of association evidence across examination cycles in longitudinal data from unrelated individuals in the Framingham Heart Study Offspring cohort. A combined analysis revealed significant independent validation of this association in both unrelated (p = 0.046) and family-based (p = 0.004) samples. The estimated risk conferred by this allele is small, and could easily be masked by small sample size, population stratification, or other confounders. These validation studies suggest that the original association is less likely to be spurious, but the failure to observe an association in every data set suggests that the effect of SNP rs7566605 on BMI may be heterogeneous across population samples.
منابع مشابه
Soy and children's health: a formula for trouble.
A SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI) by Herbert and colleagues. The association between increased BMI and homozygosity for the minor allele was first observed in data from a genome-wide association scan of 86,604 SNPs in 923 related individuals from the Framingham Heart Study offspring cohort. The ass...
متن کاملINSIG2 promoter variant, obesity markers and lipid parameters - No association in a large Slavonic Caucasian population sample.
Heritability studies have estimated the genetically attributable part of body mass index variance to be in the range of 30-70 %. Rs7566650 (G>C) single-nucleotide polymorphism (SNP) near the promoter of the INSIG2 gene has been identified as associated with body mass index. The gene product of INSIG2 is involved in regulation of fatty acid and cholesterol synthesis. In order to replicate this a...
متن کاملFine mapping of the insulin-induced gene 2 identifies a variant associated with LDL cholesterol and total apolipoprotein B levels.
BACKGROUND In a whole-genome scan, a single nucleotide polymorphism (SNP) (rs7566605) upstream of the insulin-induced gene 2 (INSIG2) was shown to influence body mass index and obesity in the Framingham Heart Study, with replication of these results in an additional 4 of 5 studies. However, other studies could not replicate the association. Because INSIG2 plays an important role in cholesterol ...
متن کاملBody mass index and composition in physical preparedness of Iranian military personnel
Purpose: Military personnel are expected to maintain the highest possible level of physical fitness to do their duties. Several factors including body composition and body mass index affect the level of their physical preparedness. The current study was designed to investigate the effect of body composition and body mass index in the level of physical preparedness of Iranian military ...
متن کاملCommon Genetic Variant of insig2 Gene rs7566605 Polymorphism Is Associated with Severe Obesity in North India
Background: Obesity is a very common disorder resulting from an imbalance between food intake and energy expenditure, and it has a substantial impact on the development of chronic diseases. The aim of this study was to examine the association of INSIG2 (rs7566605) gene polymorphism with obesity and obesity associated phenotypes in North Indian subjects. Methods: The variants were investig...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- PLoS Genetics
دوره 3 شماره
صفحات -
تاریخ انتشار 2007