The aim of this proposal is to perform follow-up genotyping of top, bone phenotype related, genotypes within the remaining ALSPAC sample in order to replicate findings from the original ALSPAC genome-wide analysis. Our definition of "top" signals of interest will take into account a three sources of information, original ALSPAC genomewide association testing, bioinformatics analysis of highest scoring SNPs and from collaborative exchange between ALSPAC and an established study for genomewide association in extremes of bone mineral density. This, in combination with results available from the one available publication on this topic, should allow us to confidently generate a list of potentially replicating loci for further follow-up. Our current estimations as to the number of loci to be followed up are approximate, however (considering the power of our studies and budget constraints) are likely to include up to 20 loci.

In terms of the recognition and analysis of reliable genetic associates of bone mineral density, this use of the ALSPAC cohort marks an important step. Given the precision and diversity of the measures available in the ALSPAC cohort, this will mark the first comprehensive analysis of top genomewide association signals from available evidence in any cohort in this way and an encouraging first use of ALSPAC genomewide genotype data.