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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

dc.contributor.authorStolk, L
dc.contributor.authorPerry, JRB
dc.contributor.authorChasman, DI
dc.contributor.authorHe, C
dc.contributor.authorMangino, M
dc.contributor.authorSulem, P
dc.contributor.authorBarbalic, M
dc.contributor.authorBroer, L
dc.contributor.authorByrne, EM
dc.contributor.authorErnst, F
dc.contributor.authorEsko, T
dc.contributor.authorFranceschini, N
dc.contributor.authorGudbjartsson, DF
dc.contributor.authorHottenga, J-J
dc.contributor.authorKraft, P
dc.contributor.authorMcArdle, PF
dc.contributor.authorPorcu, E
dc.contributor.authorShin, S-Y
dc.contributor.authorSmith, AV
dc.contributor.authorvan Wingerden, S
dc.contributor.authorZhai, G
dc.contributor.authorZhuang, WV
dc.contributor.authorAlbrecht, E
dc.contributor.authorAlizadeh, BZ
dc.contributor.authorAspelund, T
dc.contributor.authorBandinelli, S
dc.contributor.authorLauc, LB
dc.contributor.authorBeckmann, JS
dc.contributor.authorBoban, M
dc.contributor.authorBoerwinkle, E
dc.contributor.authorBroekmans, FJ
dc.contributor.authorBurri, A
dc.contributor.authorCampbell, H
dc.contributor.authorChanock, SJ
dc.contributor.authorChen, C
dc.contributor.authorCornelis, MC
dc.contributor.authorCorre, T
dc.contributor.authorCoviello, AD
dc.contributor.authord'Adamo, P
dc.contributor.authorDavies, G
dc.contributor.authorde Faire, U
dc.contributor.authorde Geus, EJC
dc.contributor.authorDeary, IJ
dc.contributor.authorDedoussis, GVZ
dc.contributor.authorDeloukas, P
dc.contributor.authorEbrahim, S
dc.contributor.authorEiriksdottir, G
dc.contributor.authorEmilsson, V
dc.contributor.authorEriksson, JG
dc.contributor.authorFauser, BCJM
dc.contributor.authorFerreli, L
dc.contributor.authorFerrucci, L
dc.contributor.authorFischer, K
dc.contributor.authorFolsom, AR
dc.contributor.authorGarcia, ME
dc.contributor.authorGasparini, P
dc.contributor.authorGieger, C
dc.contributor.authorGlazer, N
dc.contributor.authorGrobbee, DE
dc.contributor.authorHall, P
dc.contributor.authorHaller, T
dc.contributor.authorHankinson, SE
dc.contributor.authorHass, M
dc.contributor.authorHayward, C
dc.contributor.authorHeath, AC
dc.contributor.authorHofman, A
dc.contributor.authorIngelsson, E
dc.contributor.authorJanssens, ACJW
dc.contributor.authorJohnson, AD
dc.contributor.authorKarasik, D
dc.contributor.authorKardia, SLR
dc.contributor.authorKeyzer, J
dc.contributor.authorKiel, DP
dc.contributor.authorKolcic, I
dc.contributor.authorKutalik, Z
dc.contributor.authorLahti, J
dc.contributor.authorLai, S
dc.contributor.authorLaisk, T
dc.contributor.authorLaven, JSE
dc.contributor.authorLawlor, DA
dc.contributor.authorLiu, J
dc.contributor.authorLopez, LM
dc.contributor.authorLouwers, YV
dc.contributor.authorMagnusson, PKE
dc.contributor.authorMarongiu, M
dc.contributor.authorMartin, NG
dc.contributor.authorKlaric, IM
dc.contributor.authorMasciullo, C
dc.contributor.authorMcKnight, B
dc.contributor.authorMedland, SE
dc.contributor.authorMelzer, D
dc.contributor.authorMooser, V
dc.contributor.authorNavarro, P
dc.contributor.authorNewman, AB
dc.contributor.authorNyholt, DR
dc.contributor.authorOnland-Moret, NC
dc.contributor.authorPalotie, A
dc.contributor.authorParé, G
dc.contributor.authorParker, AN
dc.contributor.authorPedersen, NL
dc.contributor.authorPeeters, PHM
dc.contributor.authorPistis, G
dc.contributor.authorPlump, AS
dc.contributor.authorPolasek, O
dc.contributor.authorPop, VJM
dc.contributor.authorPsaty, BM
dc.contributor.authorRäikkönen, K
dc.contributor.authorRehnberg, E
dc.contributor.authorRotter, JI
dc.contributor.authorRudan, I
dc.contributor.authorSala, C
dc.contributor.authorSalumets, A
dc.contributor.authorScuteri, A
dc.contributor.authorSingleton, A
dc.contributor.authorSmith, JA
dc.contributor.authorSnieder, H
dc.contributor.authorSoranzo, N
dc.contributor.authorStacey, SN
dc.contributor.authorStarr, JM
dc.contributor.authorStathopoulou, MG
dc.contributor.authorStirrups, K
dc.contributor.authorStolk, RP
dc.contributor.authorStyrkarsdottir, U
dc.contributor.authorSun, YV
dc.contributor.authorTenesa, A
dc.contributor.authorThorand, B
dc.contributor.authorToniolo, D
dc.contributor.authorTryggvadottir, L
dc.contributor.authorTsui, K
dc.contributor.authorUlivi, S
dc.contributor.authorvan Dam, RM
dc.contributor.authorvan der Schouw, YT
dc.contributor.authorvan Gils, CH
dc.contributor.authorvan Nierop, P
dc.contributor.authorVink, JM
dc.contributor.authorVisscher, PM
dc.contributor.authorVoorhuis, M
dc.contributor.authorWaeber, G
dc.contributor.authorWallaschofski, H
dc.contributor.authorWichmann, HE
dc.contributor.authorWiden, E
dc.contributor.authorWijnands-van Gent, CJM
dc.contributor.authorWillemsen, G
dc.contributor.authorWilson, JF
dc.contributor.authorWolffenbuttel, BHR
dc.contributor.authorWright, AF
dc.contributor.authorYerges-Armstrong, LM
dc.contributor.authorZemunik, T
dc.contributor.authorZgaga, L
dc.contributor.authorZillikens, MC
dc.contributor.authorZygmunt, M
dc.contributor.authorLifeLines Cohort Study
dc.contributor.authorArnold, AM
dc.contributor.authorBoomsma, DI
dc.contributor.authorBuring, JE
dc.contributor.authorCrisponi, L
dc.contributor.authorDemerath, EW
dc.contributor.authorGudnason, V
dc.contributor.authorHarris, TB
dc.contributor.authorHu, FB
dc.contributor.authorHunter, DJ
dc.contributor.authorLauner, LJ
dc.contributor.authorMetspalu, A
dc.contributor.authorMontgomery, GW
dc.contributor.authorOostra, BA
dc.contributor.authorRidker, PM
dc.contributor.authorSanna, S
dc.contributor.authorSchlessinger, D
dc.contributor.authorSpector, TD
dc.contributor.authorStefansson, K
dc.contributor.authorStreeten, EA
dc.contributor.authorThorsteinsdottir, U
dc.contributor.authorUda, M
dc.contributor.authorUitterlinden, AG
dc.contributor.authorvan Duijn, CM
dc.contributor.authorVölzke, H
dc.contributor.authorMurray, A
dc.contributor.authorMurabito, JM
dc.contributor.authorVisser, JA
dc.contributor.authorLunetta, KL
dc.date.accessioned2017-02-20T13:28:10Z
dc.date.issued2012-01-22
dc.description.abstractTo newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.en_GB
dc.description.sponsorshipV.M. was a full-time employee of GlaxoSmithKline when this work was done. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetical order): Andromed, Ardana, Ferring, Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth. F.J.B. is a member of the external advisory board for Merck Serono, does consultancy work for MSD and carries out educational activities for Ferring. B.M.P. discloses (i) service on a data and safety monitoring board for a clinical trial of a device funded by the manufacturer and (ii) service on the steering committee for the Yale Open-Data Project, which is funded by Medtronic for the review of clinical trial data on recombinant morphogenic protein 2.en_GB
dc.identifier.citationVol. 44, pp. 260 - 268en_GB
dc.identifier.doi10.1038/ng.1051
dc.identifier.otherng.1051
dc.identifier.urihttp://hdl.handle.net/10871/25959
dc.language.isoenen_GB
dc.publisherNature Publishing Groupen_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/22267201en_GB
dc.subjectAge Factorsen_GB
dc.subjectDNA Helicasesen_GB
dc.subjectDNA Primaseen_GB
dc.subjectDNA Repairen_GB
dc.subjectDNA Repair Enzymesen_GB
dc.subjectDNA-Directed DNA Polymeraseen_GB
dc.subjectEuropean Continental Ancestry Groupen_GB
dc.subjectExodeoxyribonucleasesen_GB
dc.subjectFemaleen_GB
dc.subjectGenetic Locien_GB
dc.subjectGenome-Wide Association Studyen_GB
dc.subjectHumansen_GB
dc.subjectImmunityen_GB
dc.subjectMenopauseen_GB
dc.subjectPolymorphism, Single Nucleotideen_GB
dc.subjectProteinsen_GB
dc.titleMeta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathwaysen_GB
dc.typeArticleen_GB
dc.date.available2017-02-20T13:28:10Z
exeter.place-of-publicationUnited Statesen_GB
dc.descriptionThis is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.en_GB
dc.identifier.journalNature Geneticsen_GB
dc.identifier.pmcidPMC3288642
dc.identifier.pmid22267201


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