Perry, John RBDay, FelixElks, Cathy ESulem, PatrickThompson, Deborah JFerreira, TeresaHe, ChunyanChasman, DanielEsko, TõnuThorleifsson, GudmarAlbrecht, EvaAng, Wei QCorre, TanguyCousminer, Diana LFeenstra, BjarkeFranceschini, NoraGanna, AndreaJohnson, Andrew DKjellqvist, SanelaLunetta, Kathryn LMcMahon, GeorgeNolte, Ilja MPaternoster, LaviniaPorcu, EleonoraSmith, Albert VStolk, LisetteTeumer, AlexanderTšernikova, NataliaTikkanen, EmmiUlivi, SheilaWagner, Erin KAmin, NajafBierut, Laura JByrne, Enda MHottenga, Jouke-JanKoller, Daniel LMangino, MassimoPers, Tune HYerges-Armstrong, Laura MZhao, Jing HuaAndrulis, Irene LAnton-Culver, HodaAtsma, FemkeBandinelli, StefaniaBeckmann, Matthias WBenitez, JavierBlomqvist, CarlBojesen, Stig EBolla, Manjeet KBonanni, BernardoBrauch, HiltrudBrenner, HermannBuring, JulieChang-Claude, JennyChanock, StephenChen, JinhuiChenevix-Trench, GeorgiaCollée, J. MargrietCouch, Fergus JCouper, DavidCoveillo, Andrea DCox, AngelaCzene, KamilaD’adamo, Adamo PioSmith, George DaveyDe Vivo, ImmaculataDemerath, Ellen WDennis, JoeDevilee, PeterDieffenbach, Aida KDunning, Alison MEiriksdottir, GudnyEriksson, Johan GFasching, Peter AFerrucci, LuigiFlesch-Janys, DieterFlyger, HenrikForoud, TatianaFranke, LudeGarcia, Melissa EGarcía-Closas, MontserratGeller, Frankde Geus, Eco EJGiles, Graham GGudbjartsson, Daniel FGudnason, VilmundurGuénel, PascalGuo, SuiqunHall, PerHamann, UteHaring, RobinHartman, Catharina AHeath, Andrew CHofman, AlbertHooning, Maartje JHopper, John LHu, FrankHunter, DavidKarasik, DavidKiel, DouglasKnight, Julia AKosma, Veli-MattiKutalik, ZoltanLai, SandraLambrechts, DietherLindblom, AnnikaMägi, ReedikMagnusson, Patrik KMannermaa, ArtoMartin, Nicholas GMasson, GisliMcArdle, Patrick FMcArdle, Wendy LMelbye, MadsMichailidou, KyriakiMihailov, EvelinMilani, LiliMilne, Roger LNevanlinna, HeliNeven, PatrickNohr, Ellen AOldehinkel, Albertine JOostra, Ben APalotie, AarnoPeacock, MunroPedersen, Nancy LPeterlongo, PaoloPeto, JulianPharoah, Paul DPPostma, Dirkje SPouta, AnneliPylkäs, KatriRadice, PaoloRing, SusanRivadeneira, FernandoRobino, AntoniettaRose, Lynda MRudolph, AnjaSalomaa, VeikkoSanna, SerenaSchlessinger, DavidSchmidt, Marjanka KSouthey, Mellissa CSovio, UllaStampfer, MeirStöckl, DorisStorniolo, Anna MTimpson, Nicholas JTyrer, JonathanVisser, Jenny AVollenweider, PeterVölzke, HenryWaeber, GerardWaldenberger, MelanieWallaschofski, HenriWang, QinWillemsen, GonnekeWinqvist, RobertWolffenbuttel, Bruce HRWright, Margaret JBoomsma, Dorret IEcons, Michael JKhaw, Kay-TeeLoos, Ruth JFMcCarthy, Mark IMontgomery, Grant WRice, John PStreeten, Elizabeth AThorsteinsdottir, Unnurvan Duijn, Cornelia MAlizadeh, Behrooz ZBergmann, SvenBoerwinkle, EricBoyd, Heather ACrisponi, LauraGasparini, PaoloGieger, ChristianHarris, Tamara BIngelsson, ErikJärvelin, Marjo-RiittaKraft, PhillipLawlor, DebbieMetspalu, AndresPennell, Craig ERidker, PaulSnieder, HaroldSørensen, Thorkild IASpector, Tim DStrachan, David PUitterlinden, André GWareham, Nicholas JWiden, ElisabethZygmunt, MarekMurray, AnnaEaston, Douglas FStefansson, KariMurabito, Joanne MOng, Ken K2015-05-042014Perry, J. R., F. Day, C. E. Elks, P. Sulem, D. J. Thompson, T. Ferreira, C. He, et al. 2014. “Parent-of-origin specific allelic associations among 106 genomic loci for age at menarche.” Nature 514 (7520): 92-97. doi:10.1038/nature13545. http://dx.doi.org/10.1038/nature13545.0028-0836http://nrs.harvard.edu/urn-3:HUL.InstRepos:15034821Age 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 mortality1. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation2,3, 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 gamma-aminobutyric acid-B2 receptor signaling, 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.en-USJournal Article2015-05-0410.1038/nature13545