Accès ouvert déclaré
2017
article
Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk
Felix R. Day, Deborah J. Thompson, Hannes Helgason, Daniel I. Chasman, Hilary K. Finucane, Patrick Sulem, Katherine S. Ruth, Sean Whalen, Abhishek Sarkar, Eva Albrecht, Elisabeth Altmaier, Marzyeh Amini, Caterina Barbieri, Thibaud Boutin, Archie I Campbell, Ellen W. Demerath, Ayush Giri, Chunyan He, Jouke‐Jan Hottenga, Robert Karlsson, Ivana Kolchic, Po‐Ru Loh, Kathryn L. Lunetta, Massimo Mangino, Marco Brumat, George McMahon, Sarah Elizabeth Medland, Ilja Maria Nolte, Raymond Noordam, Teresa Nutile, Lavinia Paternoster, Natalia Perjakova, Eleonora Porcu, Lynda M. Rose, Katharina E. Schraut, Ayellet V. Segrè, Albert V. Smith, Lisette Stolk, Alexander Teumer, Irene Louise Andrulis, Stefania Bandinelli, Matthias W. Beckmann, Javier Benı́tez, Sven M. Bergmann, Murielle Bochud, Eric Boerwinkle, Stig E. Bojesen, Manjeet K. Bolla, Judith S. Brand, Hiltrud B. Brauch, Hermann Brenner, Linda Broer, Thomas Brüning, Julie E. Buring, Harry Campbell, Eulalia Catamo, Stephen Jacob Chanock, Georgia Chenevix‐Trench, Tanguy Corre, Fergus J. Couch, Diana L. Cousminer, Angela Cox, Laura Crisponi, Kamila Czene, George Davey Smith, Eco J. C. de Geus, Renée de Mutsert, Immaculata De Vivo, Joe Dennis, Peter Devilee, Isabel dos‐Santos‐Silva, Alison M. Dunning, Johan Gunnar Eriksson, Peter Andreas Fasching, Lindsay Fernández‐Rhodes, Luigi Ferrucci, Dieter Flesch‐Janys, Lude Franke, Marike Gabrielson, Ilaria Gandin, Graham G. Giles, Harald Grallert, Daniel Fannar Gudbjartsson, Pascal Guéne, Perr Hall, Emily Hallberg, Ute Hamann, Tamara B. Harris, Catharina A. Hartman, Gerardo Heiss, Maartje J. Hooning, John L. Hopper, Frank B. Hu, David Hunter, M. Arfan Ikram, Hae Kyung Im, Marjo‐Riitta Järvelin, Peter K. Joshi, David Karasik, Zoltán Kutalik, Geneviève Lachance, Diether Lambrechts, Claudia Langenberg, Lenore J. Launer, Joop S.E. Laven, Stefania Lenarduzzi, Jingmei Li, Penelope A. Lind, Sara Lindström, Yongmei Liu, Jian’an Luan, Graham J. Mann, Hamdi Mbarek, Mark I. McCarthy, Christa Meisinger, Thomas Meitinger, Cristina Menni, Andres Metspalu, Kyriaki Michailidou, Lili A. Milani, Roger Laughlin Milne, Grant W. Montgomery, Anna Marie Mulligan, Mike A. Nalls, Pau Navarro, Heli A. Nevanlinna, Dale R. Nyholt, Albertine J. Oldehinkel, Tracy A. O’Mara, Sandosh Padmanabhan, Aarno V. Palotie, Nancy L. Pedersen, Annette Peters, Julian Peto, Paul D.P. Pharoah, Anneli M. Pouta, Paolo Radice, Iffat Ara Sonia Rahman, Susan M. Ring, Antonietta Robino, Frits Richard Rosendaal, Igor Rudan, Rico Rueedi, Daniela Ruggiero, Cinzia Felicita Sala, Marjanka K. Schmidt, Robert A. Scott, Mitul Shah, Rossella Sorice, Melissa C. Southey, Ulla Sovio, Meir J. Stampfer, Maristella Steri, Konstantin Strauch, Toshiko Tanaka, Emmi Tikkanen, Nicholas John Timpson, Michela Traglia, Thérèse Truong, Jonathan P. Tyrer, André Gerardus Uitterlinden, Digna R. Velez Edwards, Véronique Vitart, Uwe Völker, Péter Vollenweider, Qin Wang, Elisabeth Widén, Ko Willems van Dijk, Gonneke A. H. M. Willemsen, Robert Winqvist, Bruce H. R. Wolffenbuttel, Jing Zhao, Magdalena Żołędziewska, Marek Zygmunt, Behrooz Z. Alizadeh, Dorret Irene Boomsma, Marina Ciullo, Francesco Cucca, Tõnu Esko, Nora Franceschini, Christian Gieger, Vilmundur G. Gudnason, Caroline Hayward, Peter Kraft, Debbie A. Lawlor, Patrik K. E. Magnusson, Nicholas G. Martin, Dennis O. Mook‐Kanamori, Ellen Aagaard Nohr, Ozren Polašek, David John Porteous, Alkes L. Price, Paul M. Ridker, Harold Snieder, Tim D. Spector, Doris Stöckl, Daniela Toniolo, Sheila Ulivi, Jenny A. Visser, Henry Völzke, Nicholas J. Wareham, James Fox Wilson, Amanda B. Spurdle, Unnur Thorsteindottir, Katherine S. Pollard, Douglas F. Easton, Joyce Y. Tung, Jenny C. Chang-Claude, David A. Hinds, Anna Murray, Joanne M. Murabito, Kāri Stefánsson, Ken K. Ong, John R. B. Perry, Investigators Aocs
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Le résumé fourni par la source
The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.
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Les sujets associés
Ovarian cancer diagnosis and treatmentHypothalamic control of reproductive hormonesEndometrial and Cervical Cancer Treatments