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

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

doi:10.1038/ng.3841

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

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Serval ID

serval:BIB_B4D0ABB2E939

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

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

Number

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.

OAI-PMH

oai:serval.unil.ch:BIB_B4D0ABB2E939

DOI

10.1038/ng.3841

Pubmed

28436984

Web of science

000402062300007

Create date

29/04/2017 15:48

Last modification date

18/01/2021 21:17

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

Details