DOI: 10.5061/dryad.0gb5mkmcn
title: Lifecourse genome-wide association study meta-analysis refines the critical life stages for adiposity’s influence on breast cancer risk

description: 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 &lt;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 &lt;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
 findings refine our understanding of adiposity’s role in breast cancer and
 highlight earlier life stages as critical windows for risk modulation.
description: # 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 &lt;40
 years. Summary statistics were generated separately for three age groups
 (&lt;20 years, 20–&lt;30 years, and 30–&lt;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 birth are available in a GitHub repository: \
 [https://github.com/gracemarionpower/Collaboration_MA_BMI_M2FB](https://github.com/gracemarionpower/Collaboration_MA_BMI_M2FB).\ A citable snapshot of the repository is archived on Zenodo:\ [https://doi.org/10.5281/zenodo.17178557](https://doi.org/10.5281/zenodo.17178557) ## Access information Data access for the Avon Longitudinal Study of Parents and Children (ALSPAC) operates via a managed open access system. Approved proposals are reviewed by the ALSPAC Executive Committee. Full details are provided in the ALSPAC Data Management Plan ([www.bristol.ac.uk/alspac/researchers/data-access/documents/alspac-data-management-plan.pdf](http://www.bristol.ac.uk/alspac/researchers/data-access/documents/alspac-data-management-plan.pdf)). Data from the Norwegian Mother, Father and Child (MoBa) Cohort Study is managed by the Norwegian Institute of Public Health. Access is provided upon approval from the Regional Committees for Medical and Health Research Ethics (REC), compliance with GDPR, and data owner approval. Participant consent does not allow individual-level data storage in repositories or journals. Researchers seeking access for replication must apply via [www.helsedata.no](http://www.helsedata.no/ "http://www.helsedata.no/"). To request access to data from the Trøndelag Health Study (HUNT), researchers affiliated with Norwegian research institutes can apply for the use of HUNT data and biological samples, subject to approval by the Regional Committee for Medical and Health Research Ethics. Researchers from other countries may also apply if collaborating with a Norwegian Principal Investigator. All applications are reviewed by the HUNT Data Access Committee, and successful applicants are required to enter into data access and/or material transfer agreements. Detailed information on the application process, ethical requirements, and available datasets can be found on the HUNT website ([www.ntnu.edu/hunt/data](https://www.ntnu.edu/hunt/data)). Data from Generation Scotland are available on application to an independent access committee. More information can be found on the Generation Scotland website ([www.generationscotland.org](http://www.generationscotland.org/)). Data from the Generation R Study are available upon reasonable request to the director of the Generation R Study ([generationr@erasmusmc.nl](mailto:generationr@erasmusmc.nl)), subject to local, national, and European rules and regulations. ## Human subjects data 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.