Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.

Details

Serval ID
serval:BIB_B4D0ABB2E939
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk.
Journal
Nature genetics
Author(s)
Day F.R., Thompson D.J., Helgason H., Chasman D.I., Finucane H., Sulem P., Ruth K.S., Whalen S., Sarkar A.K., Albrecht E., Altmaier E., Amini M., Barbieri C.M., Boutin T., Campbell A., Demerath E., Giri A., He C., Hottenga J.J., Karlsson R., Kolcic I., Loh P.R., Lunetta K.L., Mangino M., Marco B., McMahon G., Medland S.E., Nolte I.M., Noordam R., Nutile T., Paternoster L., Perjakova N., Porcu E., Rose L.M., Schraut K.E., Segrè A.V., Smith A.V., Stolk L., Teumer A., Andrulis I.L., Bandinelli S., Beckmann M.W., Benitez J., Bergmann S., Bochud M., Boerwinkle E., Bojesen S.E., Bolla M.K., Brand J.S., Brauch H., Brenner H., Broer L., Brüning T., Buring J.E., Campbell H., Catamo E., Chanock S., Chenevix-Trench G., Corre T., Couch F.J., Cousminer D.L., Cox A., Crisponi L., Czene K., Davey Smith G., de Geus EJCN, de Mutsert R., De Vivo I., Dennis J., Devilee P., Dos-Santos-Silva I., Dunning A.M., Eriksson J.G., Fasching P.A., Fernández-Rhodes L., Ferrucci L., Flesch-Janys D., Franke L., Gabrielson M., Gandin I., Giles G.G., Grallert H., Gudbjartsson D.F., Guénel P., Hall P., Hallberg E., Hamann U., Harris T.B., Hartman C.A., Heiss G., Hooning M.J., Hopper J.L., Hu F., Hunter D.J., Ikram M.A., Im H.K., Järvelin M.R., Joshi P.K., Karasik D., Kellis M., Kutalik Z., LaChance G., Lambrechts D., Langenberg C., Launer L.J., Laven JSE, Lenarduzzi S., Li J., Lind P.A., Lindstrom S., Liu Y., Luan J., Mägi R., Mannermaa A., Mbarek H., McCarthy M.I., Meisinger C., Meitinger T., Menni C., Metspalu A., Michailidou K., Milani L., Milne R.L., Montgomery G.W., Mulligan A.M., Nalls M.A., Navarro P., Nevanlinna H., Nyholt D.R., Oldehinkel A.J., O'Mara T.A., Padmanabhan S., Palotie A., Pedersen N., Peters A., Peto J., Pharoah PDP, Pouta A., Radice P., Rahman I., Ring S.M., Robino A., Rosendaal F.R., Rudan I., Rueedi R., Ruggiero D., Sala C.F., Schmidt M.K., Scott R.A., Shah M., Sorice R., Southey M.C., Sovio U., Stampfer M., Steri M., Strauch K., Tanaka T., Tikkanen E., Timpson N.J., Traglia M., Truong T., Tyrer J.P., Uitterlinden A.G., Edwards DRV, Vitart V., Völker U., Vollenweider P., Wang Q., Widen E., van Dijk K.W., Willemsen G., Winqvist R., Wolffenbuttel BHR, Zhao J.H., Zoledziewska M., Zygmunt M., Alizadeh B.Z., Boomsma D.I., Ciullo M., Cucca F., Esko T., Franceschini N., Gieger C., Gudnason V., Hayward C., Kraft P., Lawlor D.A., Magnusson PKE, Martin N.G., Mook-Kanamori D.O., Nohr E.A., Polasek O., Porteous D., Price A.L., Ridker P.M., Snieder H., Spector T.D., Stöckl D., Toniolo D., Ulivi S., Visser J.A., Völzke H., Wareham N.J., Wilson J.F., Spurdle A.B., Thorsteindottir U., Pollard K.S., Easton D.F., Tung J.Y., Chang-Claude J., Hinds D., Murray A., Murabito J.M., Stefansson K., Ong K.K., Perry JRB
Working group(s)
LifeLines Cohort Study, InterAct Consortium, kConFab/AOCS Investigators, Endometrial Cancer Association Consortium, Ovarian Cancer Association Consortium, PRACTICAL consortium
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
06/2017
Peer-reviewed
Oui
Volume
49
Number
6
Pages
834-841
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.

Pubmed
Web of science
Create date
29/04/2017 15:48
Last modification date
20/08/2019 15:23
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