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Genetic Insights Into the Biological Mechanisms Governing Human Ovarian Ageing

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Genetic Insights Into the Biological Mechanisms Governing Human Ovarian Ageing medRxiv preprint doi: https://doi.org/10.1101/2021.01.11.20248322; this version posted January 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Title: Genetic insights into the biological mechanisms governing human ovarian ageing Katherine S Ruth*1, Felix R Day*2, Jazib Hussain*3, Ana Martínez-Marchal*4,5, Catherine E Aiken6,7, Ajuna Azad3, Deborah J Thompson8, Hironori Abe9, Jane L Tarry-Adkins6,7, Javier Martin Gonzalez10, Annique Claringbould11, Olivier B Bakker12, Patrick Sulem13, Sandra Turon14, N Charlotte Onland-Moret15, Emil Peter Trane Hertz3,16, Pascal N Timshel17,18, Vallari Shukla3, Rehannah Borup3, Kristina W Olsen19,3, Mònica Ferrer-Roda4,5, Yan Huang4,5, Stasa Stankovic2, Paul RHJ Timmers20,21, Thomas U Ahearn22, Behrooz Z Alizadeh23, Elnaz Naderi23, Irene L Andrulis24,25, Alice M Arnold26,27, Kristan J Aronson28, Annelie Augustinsson29, Stefania Bandinelli30, Caterina M Barbieri31, Robin N Beaumont1, Heiko Becher32, Matthias W Beckmann33, Stefania Benonisdottir13, Sven Bergmann34,35, Murielle Bochud36, Eric Boerwinkle37, Stig E Bojesen38,39,40, Manjeet K Bolla41, Dorret I Boomsma42, Nicholas Bowker2, Jennifer A Brody43, Linda Broer44, Julie E Buring45,46, Archie Campbell47, Harry Campbell20, Jose E Castelao48, Eulalia Catamo49, Stephen J Chanock22, Georgia Chenevix-Trench50, Marina Ciullo51,52, Tanguy Corre36,34,35, Fergus J Couch53, Angela Cox54, Simon S Cross55, Francesco Cucca56,57, Kamila Czene58, George Davey-Smith59,60, Eco JCN de Geus42,61, Renée de Mutsert62, Immaculata De Vivo63,64, Ellen W Demerath65, Joe Dennis41, Alison M Dunning8, Miriam Dwek66, Mikael Eriksson67, Tõnu Esko68,69, Peter A Fasching70,33, Jessica D Faul71, Luigi Ferrucci72, Nora Franceschini73, Timothy M Frayling1, Manuela Gago-Dominguez74,75, Massimo Mezzavilla76, Montserrat García-Closas22, Christian Gieger77,78,79, Graham G Giles80,81,82, Harald Grallert77,78,79, Daniel F Gudbjartsson13, Vilmundur Gudnason83,84, Pascal Guénel85, Christopher A Haiman86, Niclas Håkansson87, Per Hall58, Caroline Hayward88, Chunyan He89,90, Wei He67, Gerardo Heiss73, Miya K Høffding3, John L Hopper81, Jouke J Hottenga42, Frank Hu91,64,63, David Hunter92,64,93, Mohammad A Ikram94, Rebecca D Jackson95, Micaella DR Joaquim1, Esther M John96,97, Peter K Joshi20, David Karasik98,46, Sharon LR Kardia99, Robert Karlsson100, Cari M Kitahara101, Ivana Kolcic102, Charles Kooperberg103, Peter Kraft63,104, Allison W Kurian97,96, Zoltan Kutalik36,35, Martina La Bianca49, Genevieve LaChance105, Claudia Langenberg2, Lenore J Launer106, Joop SE Laven107, Deborah A Lawlor59,60, Loic Le Marchand108, Jingmei Li58, Annika Lindblom109,110, Sara Lindstrom111, Tricia Lindstrom112, Martha Linet101, YongMei Liu113, Simin Liu114, Jian'an Luan2, Reedik Mägi69, Patrik KE Magnusson100, Massimo Mangino105,115, Arto Mannermaa116,117,118, Brumat Marco76, Jonathan Marten88, Nicholas G Martin119, Hamdi Mbarek42, Barbara McKnight27, Sarah E Medland119, Christa Meisinger78,120, Thomas Meitinger121, Cristina Menni105, Andres Metspalu69, Lili Milani69, Roger L Milne80,81,82, Grant W Montgomery122, Dennis O Mook-Kanamori62,123, Antonella Mulas56, Anna M Mulligan124,125, Alison Murray126, Mike A Nalls127, Anne Newman128, Raymond Noordam129, Teresa Nutile51, Dale R Nyholt130, Andrew F Olshan131, Håkan Olsson29, Jodie N Painter119, Alpa V Patel132, Nancy L Pedersen100, Natalia Perjakova69, Annette Peters78,79, Ulrike Peters103, Paul DP Pharoah8,41, Ozren Polasek133, Eleonora Porcu56, Bruce M Psaty43, Iffat Rahman134, Gad Rennert135, Hedy S Rennert135, Paul M Ridker45,46, Susan M Ring59,60, Antonietta Robino49, Lynda M Rose45, Frits R Rosendaal62, Jacques Rossouw136, Igor Rudan20, Rico Rueedi34,35, Daniela Ruggiero51,52, Cinzia F Sala31, Emmanouil Saloustros137, Dale P Sandler138, Serena Sanna56, Elinor J Sawyer139, Chloé Sarnowski140, David Schlessinger141, Marjanka K Schmidt142,143, Minouk J Schoemaker144, Katharina E Schraut145,20, Christopher Scott112, Saleh Shekari1, Amruta Shrikhande3, Albert V Smith83,84, Blair H Smith146, Jennifer A Smith99, Rossella Sorice51, Melissa C Southey82,147,80, Tim D Spector105, John J Spinelli148,149, Meir Stampfer63,64,91, Doris Stöckl78,150, Joyce BJ van Meurs44, Konstantin Strauch151,152, Unnur Styrkarsdottir13, Anthony J Swerdlow144,153, Toshiko Tanaka72, Lauren R Teras132, Alexander Teumer154, Unnur Þorsteinsdottir13,155, Nicholas J Timpson59,60, Daniela Toniolo31, Michela Traglia31, Melissa A Troester131, Thérèse Truong85, Jessica Tyrrell1, André G Uitterlinden44,94, Sheila Ulivi49, Celine M Vachon156, Veronique Vitart88, Uwe Völker157, Peter Vollenweider158, Henry Völzke154, Qin Wang41, Nicholas J Wareham2, Clarice R Weinberg159, David R Weir71, Amber N Wilcox22, Ko 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.01.11.20248322; this version posted January 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Willems van Dijk160,161,162, Gonneke Willemsen42, James F Wilson20,21, Bruce HR Wolffenbuttel163, Alicja Wolk87,164, Andrew R Wood1, Wei Zhao99, Marek Zygmunt165, Biobank- based Integrative Omics Study (BIOS) Consortium, eQTLGen Consortium, kConFab Investigators, The LifeLines Cohort Study,, The InterAct consortium, Lude Franke12,170, Stephen Burgess171,172, Patrick Deelen173,12, Tune H Pers17,18, Marie Louise Grøndahl19, Claus Yding Andersen174, Anna Pujol14, Andres J Lopez-Contreras3, Jeremy A Daniel16, Kari Stefansson13,155, Jenny Chang-Claude175,176, Yvonne T van der Schouw15, Kathyrn L Lunetta140,177, Daniel I Chasman45,46, Douglas F Easton8,41, Jenny A Visser44, Susan E Ozanne6, Satoshi H Namekawa9, Joanne M Murabito178,177, Ken K Ong2,179, Eva R Hoffmann*3, Anna Murray*1, Ignasi Roig*4,5, John RB Perry*2,44 * Denotes equal contribution Correspondence to Eva R Hoffmann ([email protected]), Anna Murray ([email protected]), Ignasi Roig ([email protected]) and John R B Perry ([email protected]). Author membership for listed consortia appear in the Supplementary Information. Affiliations 1 Genetics of Human Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, U.K, 2MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK, 3DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, 4Genome Integrity and Instability Group, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain., 5Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain, 6University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom, 7Department of Obstetrics and Gynaecology, University of Cambridge, Box 223, The Rosie Hospital and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0SW, UK, 8Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., 9Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, 45229, USA, 10Transgenic Core Facility, Department of Experimental Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, 11Structural and Computational Biology Unit, EMBL, Heidelberg, Germany, 12University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, The Netherlands, 13deCODE genetics/Amgen, Reykjavik, Iceland, 14Transgenic Animal Unit, Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain., 15Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands., 16The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, 17The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, København Ø, Denmark., 18Department of Epidemiology Research, Statens Serum Institut, København S, Denmark, 19Department of Obstetrics and Gynaecology, Department of Reproductive Medicine, Copenhagen University Hospital Herlev, Denmark, 20Centre for Global Health, Usher Institute, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK, 21MRC 2 medRxiv preprint doi: https://doi.org/10.1101/2021.01.11.20248322; this version posted January 15, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, Scotland, 22Division of Cancer
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