Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.

Détails

ID Serval
serval:BIB_95D27766A246
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair.
Périodique
Nature Genetics
Auteur(s)
Day F.R., Ruth K.S., Thompson D.J., Lunetta K.L., Pervjakova N., Chasman D.I., Stolk L., Finucane H.K., Sulem P., Bulik-Sullivan B., Esko T., Johnson A.D., Elks C.E., Franceschini N., He C., Altmaier E., Brody J.A., Franke L.L., Huffman J.E., Keller M.F., McArdle P.F., Nutile T., Porcu E., Robino A., Rose L.M., Schick U.M., Smith J.A., Teumer A., Traglia M., Vuckovic D., Yao J., Zhao W., Albrecht E., Amin N., Corre T., Hottenga J.J., Mangino M., Smith A.V., Tanaka T., Abecasis G.R., Andrulis I.L., Anton-Culver H., Antoniou A.C., Arndt V., Arnold A.M., Barbieri C., Beckmann M.W., Beeghly-Fadiel A., Benitez J., Bernstein L., Bielinski S.J., Blomqvist C., Boerwinkle E., Bogdanova N.V., Bojesen S.E., Bolla M.K., Borresen-Dale A.L., Boutin T.S., Brauch H., Brenner H., Brüning T., Burwinkel B., Campbell A., Campbell H., Chanock S.J., Chapman J.R., Chen Y.D., Chenevix-Trench G., Couch F.J., Coviello A.D., Cox A., Czene K., Darabi H., De Vivo I., Demerath E.W., Dennis J., Devilee P., Dörk T., Dos-Santos-Silva I., Dunning A.M., Eicher J.D., Fasching P.A., Faul J.D., Figueroa J., Flesch-Janys D., Gandin I., Garcia M.E., García-Closas M., Giles G.G., Girotto G.G., Goldberg M.S., González-Neira A., Goodarzi M.O., Grove M.L., Gudbjartsson D.F., Guénel P., Guo X., Haiman C.A., Hall P., Hamann U., Henderson B.E., Hocking L.J., Hofman A., Homuth G., Hooning M.J., Hopper J.L., Hu F.B., Huang J., Humphreys K., Hunter D.J., Jakubowska A., Jones S.E., Kabisch M., Karasik D., Knight J.A., Kolcic I., Kooperberg C., Kosma V.M., Kriebel J., Kristensen V., Lambrechts D., Langenberg C., Li J., Li X., Lindström S., Liu Y., Luan J., Lubinski J., Mägi R., Mannermaa A., Manz J., Margolin S., Marten J., Martin N.G., Masciullo C., Meindl A., Michailidou K., Mihailov E., Milani L., Milne R.L., Müller-Nurasyid M., Nalls M., Neale B.M., Nevanlinna H., Neven P., Newman A.B., Nordestgaard B.G., Olson J.E., Padmanabhan S., Peterlongo P., Peters U., Petersmann A., Peto J., Pharoah P.D., Pirastu N.N., Pirie A., Pistis G., Polasek O., Porteous D., Psaty B.M., Pylkäs K., Radice P., Raffel L.J., Rivadeneira F., Rudan I., Rudolph A., Ruggiero D., Sala C.F., Sanna S., Sawyer E.J., Schlessinger D., Schmidt M.K., Schmidt F., Schmutzler R.K., Schoemaker M.J., Scott R.A., Seynaeve C.M., Simard J., Sorice R., Southey M.C., Stöckl D., Strauch K., Swerdlow A., Taylor K.D., Thorsteinsdottir U., Toland A.E., Tomlinson I., Truong T., Tryggvadottir L., Turner S.T., Vozzi D., Wang Q., Wellons M., Willemsen G., Wilson J.F., Winqvist R., Wolffenbuttel B.B., Wright A.F., Yannoukakos D., Zemunik T., Zheng W., Zygmunt M., Bergmann S., Boomsma D.I., Buring J.E., Ferrucci L., Montgomery G.W., Gudnason V., Spector T.D., van Duijn C.M., Alizadeh B.Z., Ciullo M., Crisponi L., Easton D.F., Gasparini P.P., Gieger C., Harris T.B., Hayward C., Kardia S.L., Kraft P., McKnight B., Metspalu A., Morrison A.C., Reiner A.P., Ridker P.M., Rotter J.I., Toniolo D., Uitterlinden A.G., Ulivi S., Völzke H., Wareham N.J., Weir D.R., Yerges-Armstrong L.M., Generation Scotland, Price A.L., Price A.L., Stefansson K., Visser J.A., Ong K.K., Chang-Claude J., Murabito J.M., Perry J.R., Murray A.
Collaborateur(s)
PRACTICAL Consortium, kConFab Investigators, AOCS Investigators, EPIC-InterAct Consortium, LifeLines Cohort Study
Contributeur(s)
Generation Scotland
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
47
Numéro
11
Pages
1294-1303
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, American Recovery and Reinvestment Act ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Résumé
Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
Mots-clé
Adult, Age Factors, Aging/genetics, BRCA1 Protein/genetics, Breast Neoplasms/genetics, DNA Repair, Female, Gene Regulatory Networks/genetics, Genetic Predisposition to Disease/genetics, Genetic Variation, Genome-Wide Association Study/methods, Genomics/methods, Genotype, Humans, Hypothalamus/metabolism, Menopause/genetics, Middle Aged, Models, Genetic, Phenotype, Reproduction/genetics, Signal Transduction/genetics
Pubmed
Web of science
Création de la notice
01/12/2015 18:44
Dernière modification de la notice
03/03/2018 19:41
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