Aim:

We intend to analyse genetic variants in genes of the growth hormone pathway for their association with childhood fat mass and measures of obesity in adulthood.

Rationale:

This is a continuation of a project which has already identified an association between a genetic variant in the the growth hormone gene cluster and fat mass in ALSPAC children. We wish to expand this research to include other genes in the same pathway that may have additional effects on fat mass in order to determine (a) the importance of this pathway in childhood obesity and adult cardiovascular risk and (b) whether there is any potential for therapeutic developments. Genetic variants have been selected on the basis of functional candidacy and nominal association (pless than 0.01) with type II diabetes in the WTCCC genome-wide data. This combines the notion of prior biological knowledge with significance values in genome wide data, as typified for example by the appearance of key pharmacogenetically important genes such as PPARG in genome wide data. The growth pathway includes several drugged, druggable or possibly nutritionally modifiable targets and these may be lower down the order of hundreds of genes with modest effects in polygenic disease although potentially of more practical utility as targets..

Methods:

Genetic analyses will be carried out by KBioscience according to the standard ALSPAC arrangements for SNP genotyping. Data analysis will be carried out in STATA using regression to test per allele genetic effects.

Genetic variants and phenotypes are listed below.

Expected value of results:

Understanding the genetic mechanisms underlying obesity is an important component of researching the obesity epidemic. We hope this project will direct us to genetic variants that are both important in childhood obesity and in predisposition to adult cardiovascular disease. This work will help clarify the role of a candidate genetic pathway and provide valuable information for future research.