B639 - Replication of genomewide associates for gestational age from the Northern Finnish Birth Cohort 66 in ALSPAC - 09/04/2008

B number: 
Principal applicant name: 
Prof Mark McCarthy (University of Oxford, UK)
Dr Nic Timpson (University of Bristol, UK)
Title of project: 
Replication of genomewide associates for gestational age from the Northern Finnish Birth Cohort ('66) in ALSPAC
Proposal summary: 

Recently, a genomewide association study was undertaken within the Northern Finnish Birth Cohort ('66). This study was designed around the analysis of ~4-5000 individuals for both early phenotypes and those at a later recorded age (31 yrs). Within the cohort, there are extensive phenotypes available and as such there have been a sereis of analyses undertaken in light of the availability of genomewide data a feature only available in the last few weeks. One area of considerable interest has been with respect to the early phenotypes available for this cohort and as such, analyses on birth weight, birth length, ponderal index and gestational age have been undertaken. Of these, that concerning gestational age has yielded preliminary results of great interest (see appendix) and such that warrant immediate replication before undertaking very large-scale follow-up analyses.

The forthcoming availability of genomewide data for the a selection of the ALSPAC cohort (data which may be interrgated on an in silico basis for the initial stage of this project) majes it possible to seek initial and immediate replication of this signal. We propose initally to take the top signals for gestational age and to recover genotypes for these from the genomewide data (currently being finalised at the Sanger Institute, Cambridge). As suggested by one of the key organisers of this project (Panos Deloukas), this is a plausible exercise and the expediated delivery os select genotypes may allow for the checking of initial findings in this ALSPAC sub set.

Following this, we propose (on the basis of inference made from both the Norther Finnish data and that of the ALSPAC sub set) to take promising signals forward to replication in a sample comprised of (within ALSPAC as one of the sample bases) in both all the children and mothers. We feel that this will allow us then to formulate a roubust argument as to the possible contribution of these data to the literature surrounding the genetic predisposition to pre-term delivery (an field ALSPAC already recognises as important and contributes to directly through alternative collaborations).

This second stage of analysis would be dependent on the initial, rapid, exploration of the Finnish signal and would be derived from funding form the Oxford group.

Overall we wish to (i) seek an initial insight into the top Finnish associated signals in an expediated set of ALSPAC genomewide data (such that can be analyse immediately by Dr N Timpson) and (ii) seek permission to genotye promising signals from this stage (of which there appear naively to be 4-5) withiin the whole ALSPAC cohort.

Date proposal received: 
Wednesday, 9 April, 2008
Date proposal approved: 
Wednesday, 9 April, 2008
Genetics, Obstetrics, Pregnancy
Primary keyword: