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Refined association mapping for a quantitative trait: weight in the H19-IGF2-INS-TH region
W Zhang1, N Maniatis, S Rodriguez
1Human Genetics Division, University of Southampton, School of Medicine, Duthie Building (MP 808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. wz@soton.ac.uk
Genetic analysis identified the Insulin-like Growth Factor 2 (IGF2) gene as a key factor influencing body weight in men. Further research is needed to pinpoint the exact causal single nucleotide polymorphisms (SNPs) within IGF2.
Area of Science:
- Human Genetics
- Obesity Research
- Statistical Genomics
Background:
- Previous studies suggest genetic loci in the 11p15 region influence human body weight.
- The H19-IGF2-INS-TH locus is a region of interest for body weight regulation.
Purpose of the Study:
- To pinpoint the specific causal locus or loci influencing body weight within the 11p15 region.
- To apply association analysis using composite likelihood to a large cohort.
Main Methods:
- A cohort of 2731 UK men was genotyped for single nucleotide polymorphisms (SNPs) in IGF2, H19, INS, and TH genes.
- Composite likelihood association analysis was performed using the Malecot model for body weight.
- F tests were used to assess the superiority of regression over correlation.
Main Results:
- All evidence for association with body weight was linked to the IGF2 gene.
- A significant association was found for height-adjusted weight (P=0.007) and weight adjusted for smoking and alcohol (P=0.019).
- The confidence intervals for the causal variant encompassed most of IGF2, but not other genes in the region.
Conclusions:
- The Insulin-like Growth Factor 2 (IGF2) gene is strongly implicated as a causal factor for body weight variation.
- Further investigation of variants within IGF2 is necessary to identify the specific causal single nucleotide polymorphisms (SNPs).
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