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@ARTICLE{Ruth:170226,
      author       = {K. S. Ruth and F. R. Day and J. Hussain and A.
                      Martínez-Marchal and C. E. Aiken and A. Azad and D. J.
                      Thompson and L. Knoblochova and H. Abe and J. L.
                      Tarry-Adkins and J. M. Gonzalez and P. Fontanillas and A.
                      Claringbould and O. B. Bakker and P. Sulem and R. G. Walters
                      and C. Terao and S. Turon and M. Horikoshi and K. Lin and N.
                      C. Onland-Moret and A. Sankar and E. P. T. Hertz and P. N.
                      Timshel and V. Shukla and R. Borup and K. W. Olsen and P.
                      Aguilera and M. Ferrer-Roda and Y. Huang and S. Stankovic
                      and P. R. H. J. Timmers and T. U. Ahearn and B. Z. Alizadeh
                      and E. Naderi and I. L. Andrulis and A. M. Arnold and K. J.
                      Aronson and A. Augustinsson and S. Bandinelli and C. M.
                      Barbieri and R. N. Beaumont and H. Becher and M. W. Beckmann
                      and S. Benonisdottir and S. Bergmann and M. Bochud and E.
                      Boerwinkle and S. E. Bojesen and M. K. Bolla and D. I.
                      Boomsma and N. Bowker and J. A. Brody and L. Broer and J. E.
                      Buring and A. Campbell and H. Campbell and J. E. Castelao
                      and E. Catamo and S. J. Chanock and G. Chenevix-Trench and
                      M. Ciullo and T. Corre and F. J. Couch and A. Cox and L.
                      Crisponi and S. S. Cross and F. Cucca and K. Czene and G. D.
                      Smith and E. J. C. N. de Geus and R. de Mutsert and I. De
                      Vivo and E. W. Demerath and J. Dennis and A. M. Dunning and
                      M. Dwek and M. Eriksson and T. Esko and P. A. Fasching and
                      J. D. Faul and L. Ferrucci and N. Franceschini and T. M.
                      Frayling and M. Gago-Dominguez and M. Mezzavilla and M.
                      García-Closas and C. Gieger and G. G. Giles and H. Grallert
                      and D. F. Gudbjartsson and V. Gudnason and P. Guénel and C.
                      A. Haiman and N. Håkansson and P. Hall and C. Hayward and
                      C. He and W. He and G. Heiss and M. K. Høffding and J. L.
                      Hopper and J. J. Hottenga and F. Hu and D. Hunter and M. A.
                      Ikram and R. D. Jackson and M. D. R. Joaquim and E. M. John
                      and P. K. Joshi and D. Karasik and S. L. R. Kardia and C.
                      Kartsonaki and R. Karlsson and C. M. Kitahara and I. Kolcic
                      and C. Kooperberg and P. Kraft and A. W. Kurian and Z.
                      Kutalik and M. La Bianca and G. LaChance and C. Langenberg
                      and L. J. Launer and J. S. E. Laven and D. A. Lawlor and L.
                      Le Marchand and J. Li and A. Lindblom and S. Lindstrom and
                      T. Lindstrom and M. Linet and Y. Liu and S. Liu and J. Luan
                      and R. Mägi and P. K. E. Magnusson and M. Mangino and A.
                      Mannermaa and B. Marco and J. Marten and N. G. Martin and H.
                      Mbarek and B. McKnight and S. E. Medland and C. Meisinger
                      and T. Meitinger and C. Menni and A. Metspalu and L. Milani
                      and R. L. Milne and G. W. Montgomery and D. O. Mook-Kanamori
                      and A. Mulas and A. M. Mulligan and A. Murray and M. A.
                      Nalls and A. Newman and R. Noordam and T. Nutile and D. R.
                      Nyholt and A. F. Olshan and H. Olsson and J. N. Painter and
                      A. V. Patel and N. L. Pedersen and N. Perjakova and A.
                      Peters and U. Peters and P. D. P. Pharoah and O. Polasek and
                      E. Porcu and B. M. Psaty and I. Rahman and G. Rennert and H.
                      S. Rennert and P. M. Ridker and S. M. Ring and A. Robino and
                      L. M. Rose and F. R. Rosendaal and J. Rossouw and I. Rudan
                      and R. Rueedi and D. Ruggiero and C. F. Sala and E.
                      Saloustros and D. P. Sandler and S. Sanna and E. J. Sawyer
                      and C. Sarnowski and D. Schlessinger and M. K. Schmidt and
                      M. J. Schoemaker and K. E. Schraut and C. Scott and S.
                      Shekari and A. Shrikhande and A. V. Smith and B. H. Smith
                      and J. A. Smith and R. Sorice and M. C. Southey and T. D.
                      Spector and J. J. Spinelli and M. Stampfer and D. Stöckl
                      and J. B. J. van Meurs and K. Strauch and U. Styrkarsdottir
                      and A. J. Swerdlow and T. Tanaka and L. R. Teras and A.
                      Teumer and U. Þorsteinsdottir and N. J. Timpson and D.
                      Toniolo and M. Traglia and M. A. Troester and T. Truong and
                      J. Tyrrell and A. G. Uitterlinden and S. Ulivi and C. M.
                      Vachon and V. Vitart and U. Völker and P. Vollenweider and
                      H. Völzke and Q. Wang and N. J. Wareham and C. R. Weinberg
                      and D. R. Weir and A. N. Wilcox and K. W. van Dijk and G.
                      Willemsen and J. F. Wilson and B. H. R. Wolffenbuttel and A.
                      Wolk and A. R. Wood and W. Zhao and M. Zygmunt and Z. Chen
                      and L. Li and L. Franke and S. Burgess and P. Deelen and T.
                      H. Pers and M. L. Grøndahl and C. Y. Andersen and A. Pujol
                      and A. J. Lopez-Contreras and J. A. Daniel and K. Stefansson
                      and J. Chang-Claude$^*$ and Y. T. van der Schouw and K. L.
                      Lunetta and D. I. Chasman and D. F. Easton and J. A. Visser
                      and S. E. Ozanne and S. H. Namekawa and P. Solc and J. M.
                      Murabito and K. K. Ong and E. R. Hoffmann and A. Murray and
                      I. Roig and J. R. B. Perry},
      collaboration = {B. I. O. Study and e. Consortium and B. J. Project and C.
                      K. B. C. Group and k. Investigators and L. C. Study and I.
                      consortium and 2. R. Team},
      title        = {{G}enetic insights into biological mechanisms governing
                      human ovarian ageing.},
      journal      = {Nature},
      volume       = {596},
      number       = {7872},
      issn         = {1476-4687},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2021-01834},
      pages        = {393-397},
      year         = {2021},
      note         = {2021 Aug;596(7872):393-397},
      abstract     = {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.},
      cin          = {C020},
      ddc          = {500},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34349265},
      doi          = {10.1038/s41586-021-03779-7},
      url          = {https://inrepo02.dkfz.de/record/170226},
}