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Perry, J.R.B.* ; Day, F.* ; Elks, C.E.* ; Sulem, P.* ; Thompson, D.J.* ; Ferreira, T.* ; He, C.* ; Chasman, D.I.* ; Esko, T.* ; Thorleifsson, G.* ; Albrecht, E. ; Ang, W.Q.* ; Corre, T.* ; Cousminer, D.L.* ; Feenstra, B.* ; Franceschini, N.* ; Ganna, A.* ; Johnson, A.D.* ; Kjellqvist, S.* ; Lunetta, K.L.* ; McMahon, G.* ; Nolte, I.M.* ; Paternoster, L.* ; Porcu, E.* ; Smith, A.V.* ; Stolk, L.* ; Teumer, A.* ; Tsernikova, N.* ; Tikkanen, E.* ; Ulivi, S.* ; Wagner, E.K.* ; Amin, N.* ; Bierut, L.J.* ; Byrne, E.M.* ; Hottenga, J.-J.* ; Koller, D.L.* ; Mangino, M.* ; Pers, T.H.* ; Yerges-Armstrong, L.M.* ; Zhao, J.H.* ; Andrulis, I.L.* ; Anton-Culver, H.* ; Atsma, F.* ; Bandinelli, S.* ; Beckmann, M.W.* ; Benítez, J.* ; Blomqvist, C.* ; Bojesen, S.E.* ; Bolla, M.K.* ; Bonanni, B.* ; Brauch, H.* ; Brenner, H.* ; Buring, J.E.* ; Chang-Claude, J.* ; Chanock, S.* ; Chen, J.* ; Chenevix-Trench, G.* ; Collee, J.M.* ; Couch, F.J.* ; Couper, D.* ; Coviello, A.D.* ; Cox, A.* ; Czene, K.* ; D’adamo, A.P.* ; Smith, G.D.* ; de Vivo, I.* ; Demerath, E.W.* ; Dennis, J.* ; Devilee, P.* ; Dieffenbach, A.K.* ; Dunning, A.M.* ; Eiriksdottir, G.* ; Eriksson, J.G.* ; Fasching, P.A.* ; Ferrucci, L.* ; Flesch-Janys, D.* ; Flyger, H.* ; Foroud, T.* ; Franke, L.* ; Garcia, M.E.* ; Garcia-Closas, M.* ; Geller, F.* ; de Geus, E.J.* ; Giles, G.G.* ; Gudbjartsson, D.F.* ; Gudnason, V.* ; Guénel, P.* ; Guo, S.* ; Hall, P.* ; Hamann, U.* ; Haring, R.* ; Hartman, C.A.* ; Heath, A.C.* ; Hofman, A.* ; Hooning, M.J.* ; Hopper, J.L.* ; Hu, F.B.* ; Hunter, D.J.* ; Karasik, D.* ; Kiel, D.P.* ; Knight, J.A.* ; Kosma, V.M.* ; Kutalik, Z.* ; Lai, S.* ; Lambrechts, D.* ; Lindblom, A.* ; Mägi, R.* ; Magnusson, P.K.* ; Mannermaa, A.* ; Martin, N.G.* ; Masson, G.* ; McArdle, P.F.* ; McArdle, W.L.* ; Melbye, M.* ; Michailidou, K.* ; Mihailov, E.* ; Milani, L.* ; Milne, R.L.* ; Nevanlinna, H.* ; Neven, P.* ; Nohr, E.A.* ; Oldehinkel, A.J.* ; Oostra, B.A.* ; Palotie, A.* ; Peacock, M.* ; Pedersen, N.L.* ; Peterlongo, P.* ; Peto, J.* ; Pharoah, P.D.P.* ; Postma, D.S.* ; Pouta, A.* ; Pylkäs, K.* ; Radice, P.* ; Ring, S.* ; Rivadeneira, F.* ; Robino, A.* ; Rose, L.M.* ; Rudolph, A.* ; Salomaa, V.* ; Sanna, S.* ; Schlessinger, D.* ; Schmidt, M.K.* ; Southey, M.C.* ; Sovio, U.* ; Stampfer, M.* ; Stöckl, D. ; Storniolo, A.* ; Timpson, N.J.* ; Tyrer, J.* ; Visser, J.A.* ; Vollenweider, P.* ; Völzke, H.* ; Waeber, G.* ; Waldenberger, M. ; Wallaschofski, H.* ; Wang, Q.* ; Willemsen, G.* ; Winqvist, R.* ; Wolffenbuttel, B.H.R.* ; Wright, M.J.* ; Boomsma, D.I.* ; Econs, M.J.* ; Khaw, K.-T.* ; Loos, R.J.F.* ; McCarthy, M.I.* ; Montgomery, G.W.* ; Rice, J.P.* ; Streeten, E.A.* ; Thorsteinsdottir, U.* ; van Duijn, C.M.* ; Alizadeh, B.Z.* ; Bergmann, S.* ; Boerwinkle, E.* ; Boyd, H.A.* ; Crisponi, L.* ; Gasparini, P.* ; Gieger, C. ; Harris, T.B.* ; Ingelsson, E.* ; Järvelin, M.-R.* ; Kraft, P.* ; Lawlor, D.* ; Metspalu, A.* ; Pennell, C.E.* ; Ridker, P.M.* ; Snieder, H.* ; Sørensen, T.I.* ; Spector, T.D.* ; Strachan, D.P.* ; Uitterlinden, A.G.* ; Wareham, N.J.* ; Widen, E.* ; Zygmunt, M.* ; Murray, A.* ; Easton, D.F.* ; Stefansson, K.* ; Murabito, J.M.* ; Ong, K.K.*

Parent-of-origin specific allelic associations among 106 genomic1 loci for age at menarche.

Nature 514, 92-97 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10−8) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Central Precocious Puberty; Human Prefrontal Cortex; Breast-cancer Risk; Gene-expression; Wide Association; Metaanalysis; Disease; Variants; Cells; Reveals
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Journal Nature
Quellenangaben Volume: 514, Issue: 7520, Pages: 92-97 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology II (EPI2)