RT Journal Article
T1 Genetic insights into biological mechanisms governing human ovarian ageing.
A1 Ruth, Katherine S
A1 Day, Felix R
A1 Hussain, Jazib
A1 Martínez-Marchal, Ana
A1 Aiken, Catherine E
A1 Azad, Ajuna
A1 Thompson, Deborah J
A1 Knoblochova, Lucie
A1 Abe, Hironori
A1 Tarry-Adkins, Jane L
A1 Gonzalez, Javier Martin
A1 Fontanillas, Pierre
A1 Claringbould, Annique
A1 Bakker, Olivier B
A1 Sulem, Patrick
A1 Walters, Robin G
A1 Terao, Chikashi
A1 Turon, Sandra
A1 Horikoshi, Momoko
A1 Lin, Kuang
A1 Onland-Moret, N Charlotte
A1 Sankar, Aditya
A1 Hertz, Emil Peter Thrane
A1 Timshel, Pascal N
A1 Shukla, Vallari
A1 Borup, Rehannah
A1 Olsen, Kristina W
A1 Aguilera, Paula
A1 Ferrer-Roda, Mònica
A1 Huang, Yan
A1 Stankovic, Stasa
A1 Timmers, Paul R H J
A1 Ahearn, Thomas U
A1 Alizadeh, Behrooz Z
A1 Naderi, Elnaz
A1 Andrulis, Irene L
A1 Arnold, Alice M
A1 Aronson, Kristan J
A1 Augustinsson, Annelie
A1 Bandinelli, Stefania
A1 Barbieri, Caterina M
A1 Beaumont, Robin N
A1 Becher, Heiko
A1 Beckmann, Matthias W
A1 Benonisdottir, Stefania
A1 Bergmann, Sven
A1 Bochud, Murielle
A1 Boerwinkle, Eric
A1 Bojesen, Stig E
A1 Bolla, Manjeet K
A1 Boomsma, Dorret I
A1 Bowker, Nicholas
A1 Brody, Jennifer A
A1 Broer, Linda
A1 Buring, Julie E
A1 Campbell, Archie
A1 Campbell, Harry
A1 Castelao, Jose E
A1 Catamo, Eulalia
A1 Chanock, Stephen J
A1 Chenevix-Trench, Georgia
A1 Ciullo, Marina
A1 Corre, Tanguy
A1 Couch, Fergus J
A1 Cox, Angela
A1 Crisponi, Laura
A1 Cross, Simon S
A1 Cucca, Francesco
A1 Czene, Kamila
A1 Smith, George Davey
A1 de Geus, Eco J C N
A1 de Mutsert, Renée
A1 De Vivo, Immaculata
A1 Demerath, Ellen W
A1 Dennis, Joe
A1 Dunning, Alison M
A1 Dwek, Miriam
A1 Eriksson, Mikael
A1 Esko, Tõnu
A1 Fasching, Peter A
A1 Faul, Jessica D
A1 Ferrucci, Luigi
A1 Franceschini, Nora
A1 Frayling, Timothy M
A1 Gago-Dominguez, Manuela
A1 Mezzavilla, Massimo
A1 García-Closas, Montserrat
A1 Gieger, Christian
A1 Giles, Graham G
A1 Grallert, Harald
A1 Gudbjartsson, Daniel F
A1 Gudnason, Vilmundur
A1 Guénel, Pascal
A1 Haiman, Christopher A
A1 Håkansson, Niclas
A1 Hall, Per
A1 Hayward, Caroline
A1 He, Chunyan
A1 He, Wei
A1 Heiss, Gerardo
A1 Høffding, Miya K
A1 Hopper, John L
A1 Hottenga, Jouke J
A1 Hu, Frank
A1 Hunter, David
A1 Ikram, Mohammad A
A1 Jackson, Rebecca D
A1 Joaquim, Micaella D R
A1 John, Esther M
A1 Joshi, Peter K
A1 Karasik, David
A1 Kardia, Sharon L R
A1 Kartsonaki, Christiana
A1 Karlsson, Robert
A1 Kitahara, Cari M
A1 Kolcic, Ivana
A1 Kooperberg, Charles
A1 Kraft, Peter
A1 Kurian, Allison W
A1 Kutalik, Zoltan
A1 La Bianca, Martina
A1 LaChance, Genevieve
A1 Langenberg, Claudia
A1 Launer, Lenore J
A1 Laven, Joop S E
A1 Lawlor, Deborah A
A1 Le Marchand, Loic
A1 Li, Jingmei
A1 Lindblom, Annika
A1 Lindstrom, Sara
A1 Lindstrom, Tricia
A1 Linet, Martha
A1 Liu, YongMei
A1 Liu, Simin
A1 Luan, Jian'an
A1 Mägi, Reedik
A1 Magnusson, Patrik K E
A1 Mangino, Massimo
A1 Mannermaa, Arto
A1 Marco, Brumat
A1 Marten, Jonathan
A1 Martin, Nicholas G
A1 Mbarek, Hamdi
A1 McKnight, Barbara
A1 Medland, Sarah E
A1 Meisinger, Christa
A1 Meitinger, Thomas
A1 Menni, Cristina
A1 Metspalu, Andres
A1 Milani, Lili
A1 Milne, Roger L
A1 Montgomery, Grant W
A1 Mook-Kanamori, Dennis O
A1 Mulas, Antonella
A1 Mulligan, Anna M
A1 Murray, Alison
A1 Nalls, Mike A
A1 Newman, Anne
A1 Noordam, Raymond
A1 Nutile, Teresa
A1 Nyholt, Dale R
A1 Olshan, Andrew F
A1 Olsson, Håkan
A1 Painter, Jodie N
A1 Patel, Alpa V
A1 Pedersen, Nancy L
A1 Perjakova, Natalia
A1 Peters, Annette
A1 Peters, Ulrike
A1 Pharoah, Paul D P
A1 Polasek, Ozren
A1 Porcu, Eleonora
A1 Psaty, Bruce M
A1 Rahman, Iffat
A1 Rennert, Gad
A1 Rennert, Hedy S
A1 Ridker, Paul M
A1 Ring, Susan M
A1 Robino, Antonietta
A1 Rose, Lynda M
A1 Rosendaal, Frits R
A1 Rossouw, Jacques
A1 Rudan, Igor
A1 Rueedi, Rico
A1 Ruggiero, Daniela
A1 Sala, Cinzia F
A1 Saloustros, Emmanouil
A1 Sandler, Dale P
A1 Sanna, Serena
A1 Sawyer, Elinor J
A1 Sarnowski, Chloé
A1 Schlessinger, David
A1 Schmidt, Marjanka K
A1 Schoemaker, Minouk J
A1 Schraut, Katharina E
A1 Scott, Christopher
A1 Shekari, Saleh
A1 Shrikhande, Amruta
A1 Smith, Albert V
A1 Smith, Blair H
A1 Smith, Jennifer A
A1 Sorice, Rossella
A1 Southey, Melissa C
A1 Spector, Tim D
A1 Spinelli, John J
A1 Stampfer, Meir
A1 Stöckl, Doris
A1 van Meurs, Joyce B J
A1 Strauch, Konstantin
A1 Styrkarsdottir, Unnur
A1 Swerdlow, Anthony J
A1 Tanaka, Toshiko
A1 Teras, Lauren R
A1 Teumer, Alexander
A1 Þorsteinsdottir, Unnur
A1 Timpson, Nicholas J
A1 Toniolo, Daniela
A1 Traglia, Michela
A1 Troester, Melissa A
A1 Truong, Thérèse
A1 Tyrrell, Jessica
A1 Uitterlinden, André G
A1 Ulivi, Sheila
A1 Vachon, Celine M
A1 Vitart, Veronique
A1 Völker, Uwe
A1 Vollenweider, Peter
A1 Völzke, Henry
A1 Wang, Qin
A1 Wareham, Nicholas J
A1 Weinberg, Clarice R
A1 Weir, David R
A1 Wilcox, Amber N
A1 van Dijk, Ko Willems
A1 Willemsen, Gonneke
A1 Wilson, James F
A1 Wolffenbuttel, Bruce H R
A1 Wolk, Alicja
A1 Wood, Andrew R
A1 Zhao, Wei
A1 Zygmunt, Marek
A1 Biobank-based Integrative Omics Study (BIOS) Consortium, 
A1 eQTLGen Consortium, 
A1 Biobank Japan Project, 
A1 China Kadoorie Biobank Collaborative Group, 
A1 kConFab Investigators, 
A1 LifeLines Cohort Study, 
A1 InterAct consortium, 
A1 23andMe Research Team, 
A1 Chen, Zhengming
A1 Li, Liming
A1 Franke, Lude
A1 Burgess, Stephen
A1 Deelen, Patrick
A1 Pers, Tune H
A1 Grøndahl, Marie Louise
A1 Andersen, Claus Yding
A1 Pujol, Anna
A1 Lopez-Contreras, Andres J
A1 Daniel, Jeremy A
A1 Stefansson, Kari
A1 Chang-Claude, Jenny
A1 van der Schouw, Yvonne T
A1 Lunetta, Kathryn L
A1 Chasman, Daniel I
A1 Easton, Douglas F
A1 Visser, Jenny A
A1 Ozanne, Susan E
A1 Namekawa, Satoshi H
A1 Solc, Petr
A1 Murabito, Joanne M
A1 Ong, Ken K
A1 Hoffmann, Eva R
A1 Murray, Anna
A1 Roig, Ignasi
A1 Perry, John R B
AB Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
YR 2021
FD 2021-08-04
LK http://hdl.handle.net/10668/18292
UL http://hdl.handle.net/10668/18292
LA en
DS RISalud
RD May 9, 2025