gms | German Medical Science

Kongress Medizin und Gesellschaft 2007

17. bis 21.09.2007, Augsburg

The association of a SNP upstream of INSIG2 with Body Mass Index is reproduced in several but not all cohorts

Meeting Abstract

  • Iris M Heid - GSF-Institut für Epidemiologie, Neuherberg
  • Helen Lyon - Broad Institute of Harvard and MIT, Boston
  • Valur Emilsson - deCODE genetics, Reykjavik
  • Anke Hinney - Rheinische Kliniken Essen, Essen
  • Jennifer Lasky-Su - Harvard Medical School, Boston
  • Xiaofeng Zhu - Case Western Reserve University, Cleveland
  • Juan C. Celedón - Harvard Medical School, Boston
  • H. Erich Wichmann - GSF-Institut für Epidemiologie, Neuherberg
  • Johannes Hebebrand - Rheinische Kliniken Essen, Essen
  • Kari Stefansson - deCODE genetics, Reykjavik
  • Christoph Lange - Harvard Medical School, Boston
  • Joel Hirschhorn - Children’s Hospital, Boston

Kongress Medizin und Gesellschaft 2007. Augsburg, 17.-21.09.2007. Düsseldorf: German Medical Science GMS Publishing House; 2007. Doc07gmds141

The electronic version of this article is the complete one and can be found online at:

Published: September 6, 2007

© 2007 Heid et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



A SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI)[1]. 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 (FHS) offspring cohort. The association was reproduced in 4 additional cohorts, but was not seen in a fifth cohort. To further assess the general reproducibility of this association, we genotyped rs7566605 in 9 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 four 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.