Lifecourse genome-wide association study meta-analysis refines the critical life stages for adiposity’s influence on breast cancer risk

Previous evidence suggests that higher prepubertal adiposity protects against breast cancer risk. Whether this protection extends into early adulthood remains uncertain. We conducted genome-wide association studies on body mass index (BMI) in nulliparous women from menarche to <40 years across five cohorts, with additional analyses in three sub-intervals of this life stage. Results were meta-analysed, and two-sample univariable and multivariable Mendelian randomisation was applied within a life-course framework to assess the effect of BMI on breast cancer risk. Between menarche and <40 years, we observed heterogeneity in genetic effects. Genome-wide correlations further suggest BMI during this early adult period may be partly influenced by distinct genetic factors compared with adiposity at other life stages. Higher genetically proxied BMI between menarche and 40 years reduced breast cancer risk. This protective effect attenuated after adjusting for prepubertal adiposity. These fi..., , # Lifecourse genome-wide association study meta-analysis refines the critical life stages for adiposity’s influence on breast cancer risk

Dataset DOI: [10.5061/dryad.0gb5mkmcn](https://doi.org/10.5061/dryad.0gb5mkmcn)

## Description of the data and file structure

Four files: 
- gwas_metaanalysis_bmi_f_1019
- gwas_metaanalysis_bmi_f_2029
- gwas_metaanalysis_bmi_f_3039
- gwas_metaanalysis_bmi_f_total

The data consist of meta-analysed genome-wide association study (GWAS) summary statistics for BMI in nulliparous females between menarche and age <40 years. Summary statistics were generated separately for three age groups (<20 years, 20–<30 years, and 30–<40 years) using data from five population-based cohorts (ALSPAC, HUNT, MoBa, Generation R, and Generation Scotland), and combined using fixed-effect meta-analysis.

## Code/software

The standard operating procedure (SOP) and analysis scripts used to conduct the genome-wide association study (GWAS) of BMI between menarche and first birt..., All participants provided informed consent for cohort participation and for the use of their de-identified data in research. Only summary-level genome-wide association study (GWAS) statistics, which contain no individual-level information, are shared in this repository. No directly identifying variables are included. All data were aggregated across large participant groups, and all cohort-level governance policies regarding the sharing of de-identified data were strictly followed prior to public release.