As part of an approved UK10K secondary proposal, we aim to perform an age of menarche whole-genome meta-analysis between ALSPAC and Twins UK. A UK10K secondary proposal covers any phenotype not included as a 'core' trait intended to be published as part of UK10K. We aim to analyse menarche and publish as a separate satelite paper at a similar time to the main UK10K effort.

There are two genetic datasets used in this project (that are already available within UK10K):

The ALSPAC UK10K sequence genotypes

Imputed UK10K genotypes from the wider ALSPAC GWAS sample

(We will perform two models, using the same statistical parameters used by the ReproGen consortium.

Model A: Menarche ~ SNP + Birth year

Model B: Menarche ~ SNP + Birth year + BMI (closest to age at menarche)

Model C: Menarche ~ SNP + Birth year + BMI (furthest time point from menarche available)

Similar to the core analyses in UK10K, we aim to perform a 4-way meta-analysis of the following strata:

Discovery sequence genotypes in ALSPAC

Discovery sequence genotypes in Twins UK

Imputed UK10K sequence genotypes from wider GWAS in ALSPAC

Imputed UK10K sequence genotypes from wider GWAS in Twins UK

We plan to share both individual level data (where possible) and summary level SNP results for meta-analysis. Only analysts registered on a UK10K data access agreement will be using the data - currently covers John Perry (KCL side) and Carolina Bonilla (ALSPAC side) for this project.