Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.
Day FR, Ruth KS, Thompson DJ et al.
Publication Details
Comprehensive information about this research publication
Authors
Abstract
Summary of the research findings
Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
up to 69,626 European ancestry women
Study Statistics
Key metrics and study information
Analysis
Comprehensive review of health and genetic findings
Important Disclaimer: This review has been performed semi-automatically and is provided for informational purposes only. While we strive for accuracy, this analysis may contain errors, omissions, or misinterpretations of the original research. DNA Genics disclaims all liability for any inaccuracies, errors, or consequences arising from the use of this information. Users should independently verify all information and consult original research publications before making any decisions based on this content. This analysis is not intended as a substitute for professional scientific review or medical advice.
Analysis In Progress
Our analysis of this publication is currently being prepared. Please check back soon for comprehensive insights into the health and genetic findings discussed in this research.
Summary
Key Findings
Health Insights
Disease Analysis
Genetic Trait Analysis
Clinical Relevance
Scientific Assessment
Related Publications
Other publications that may be of interest
A genome-wide association study of mass spectrometry proteomics using a nanoparticle enrichment platform.
Suhre K
Nat Genet
HV102 protein level (protein group normalized intensity)
Inference of chronic obstructive pulmonary disease with deep learning on raw spirograms identifies new genetic loci and improves risk models.
Cosentino J
Nat Genet
Chronic obstructive pulmonary disease liability (machine learning-based score)
A genetic map of human metabolism across the allele frequency spectrum.
Zoodsma M
Nat Genet
Free cholesterol in small VLDL (PGS-adjusted)
Large-scale genome-wide analyses of stuttering.
Polikowsky HG
Nat Genet
Stuttering
Genome-wide association study and polygenic risk prediction of hypothyroidism.
Rand SA
Nat Genet
Thyroid stimulating hormone levels
Explore More Research
Discover the latest findings in health and genetic research