Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Genetic insights into biological mechanisms governing human ovarian ageing

Katherine S. Ruth, Felix R. Day, Jazib Hussain, Ana Martínez-Marchal, Catherine Aiken, Ajuna Azad, Deborah J. Thompson, Lucie Knoblochová, Hironori Abe, Jane L. Tarry‐Adkins, Javier Martín‐González, Pierre Fontanillas, Annique Claringbould, Olivier B. Bakker, Patrick Sulem, Robin Walters, Chikashi Terao, Sandra Turon, Momoko Horikoshi, Kuang Lin, N. Charlotte Onland‐Moret, Aditya Sankar, Emil Peter Thrane Hertz, Pascal Timshel, Vallari Shukla, Rehannah Borup, Kristina Wendelboe Olsen, Paula Aguilera, Mònica Ferrer‐Roda, Yan Huang, Stasa Stankovic, Paul R. H. J. Timmers, Thomas U. Ahearn, Behrooz Z. Alizadeh, Elnaz Naderi, Irene L. Andrulis, Alice M. Arnold, Kristan J. Aronson, Annelie Augustinsson, Stefania Bandinelli, Caterina Barbieri, Robin N. Beaumont, Heiko Becher, Matthias W. Beckmann, Stefania Benónísdóttir, Sven Bergmann, Murielle Bochud, Eric Boerwinkle, Stig E. Bojesen, Manjeet K. Bolla, Dorret I. Boomsma, Nicholas Bowker, Jennifer A. Brody, Linda Broer, Julie E. Buring, Archie Campbell, Harry Campbell, Jose E. Castelao, Eulalia Catamo, Stephen J. Chanock, Georgia Chenevix‐Trench, Marina Ciullo, Tanguy Corre, Fergus J. Couch, Angela Cox, Laura Crisponi, Simon S. Cross, Francesco Cucca, Kamila Czene, George Davey Smith, Eco J. C. de Geus, Renée de Mutsert, Immaculata De Vivo, Ellen W. Demerath, Joe Dennis, Alison M. Dunning, Miriam Dwek, Mikael Eriksson, Tõnu Esko, Peter A. Fasching, Jessica D. Faul, Luigi Ferrucci, Nora Franceschini, Timothy M. Frayling, Manuela Gago-Domínguez, Massimo Mezzavilla, Montserrat García‐Closas, Christian Gieger, Graham G. Giles, Harald Grallert, Daníel F. Guðbjartsson, Vilmundur Guðnason, Pascal Guénel, Christopher A. Haiman, Niclas Håkansson, Per Hall, Caroline Hayward, Chunyan He, Wei He, Gerardo Heiss

Nature · 2021

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Summary

This large international GWAS study identified genetic variants and biological mechanisms governing human ovarian ageing, integrating multiple cohorts to characterise pathways underlying reproductive senescence. The findings provide insights into the molecular basis of menopause timing and ovarian reserve decline, as suggested by the genetic architecture revealed. The work may inform understanding of female reproductive health trajectories and ageing processes, though clinical translation remains uncertain.

UK applicability

The findings are applicable to UK populations as they derive from large international cohorts inclusive of European ancestry data. Results may inform clinical assessment and counselling regarding reproductive ageing in UK clinical practice, though direct policy or farming-systems implications are absent.

Key measures

Age at natural menopause, ovarian reserve (anti-Müllerian hormone levels), genetic variants, biological pathways and mechanisms

Outcomes reported

The study identified genetic variants and biological pathways associated with ovarian ageing, measured through age at natural menopause and ovarian reserve markers. It inferred mechanistic insights into reproductive senescence through genome-wide association analysis across large international cohorts.

Theme
Nutrition & health
Subject
Other / interdisciplinary
Study type
Research
Study design
Genome-wide association study (GWAS) / Observational cohort
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s41586-021-03779-7
Catalogue ID
BFmor3gaas-orppmw

Topic tags

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