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

Perry, J.R.; 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.; Tšernikova, 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.; Hua Zhao, J.; Andrulis, I.L.; Anton-Culver, H.; Atsma, F.; Bandinelli, S.; Beckmann, M.W.; Benitez, 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.; Collée, J.M.; Couch, F.J.; Couper, D.; Coviello, A.D.; Cox, A.; Czene, K.; D'adamo, A.P.; Davey Smith, G.; 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.; García-Closas, M.; Geller, F.; de Geus, E.E.; 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.; 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.J.; Stöckl, D.; Storniolo, A.M.; 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.; Wright, M.J.; Boomsma, D.I.; Econs, M.J.; Khaw, K.T.; Loos, R.J.; 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.

doi:10.1038/nature13545

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

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Download: BIB_7816C9E4E3E5.P001.pdf (995.53 [Ko])
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Serval ID

serval:BIB_7816C9E4E3E5

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature

Author(s)

Perry J.R., 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., Tšernikova 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., Hua Zhao J., Andrulis I.L., Anton-Culver H., Atsma F., Bandinelli S., Beckmann M.W., Benitez 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., Collée J.M., Couch F.J., Couper D., Coviello A.D., Cox A., Czene K., D'adamo A.P., Davey Smith G., 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., García-Closas M., Geller F., de Geus E.E., 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., 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.J., Stöckl D., Storniolo A.M., 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., Wright M.J., Boomsma D.I., Econs M.J., Khaw K.T., Loos R.J., 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.

Working group(s)

Australian Ovarian Cancer Study, GENICA Network, kConFab, LifeLines Cohort Study, InterAct Consortium, Early Growth Genetics (EGG) Consortium

Contributor(s)

Cousminer D.L., Stergiakouli E., Berry D.J., Ang W., Groen-Blokhuis M.M., Körner A., Siitonen N., Ntalla I., Marinelli M., Perry J.R., Kettunen J., Jansen R., Surakka I., Timpson N.J., Ring S., McMahon G., Power C., Wang C., Kähönen M., Viikari J., Lehtimäki T., Middeldorp C.M., Hulshoff Pol H.E., Neef M., Weise S., Pahkala K., Niinikoski H., Zeggini E., Panoutsopoulou K., Bustamante M., Penninx B.W., Murabito J., Torrent M., Dedoussis G.V., Kiess W., Boomsma D.I., Pennell C.E., Raitakari O.T., Hyppönen E., Davey Smith G., Ripatti S., McCarthy M.I., Widén E., Alizadeh B.Z., de Boer R.A., Boezen H.M., Bruinenberg M., Franke L., van der Harst P., Hillege H.L., van der Klauw M.M., Navis G., Ormel J., Postma D., Rosmalen J.G., Slaets J.P., Snieder H., Stolk R.P., Wolffenbuttel B.H., Wijmenga C., Forouhi N., Kerrison N.D., Langenberg C., Scott R.A., Sharp S.J., Sims M., Barroso I., Deloukas P., McCarthy M.I., Arriola L., Balkau B., Barricarte A., Boeing H., Franks P.W., Gonzalez C., Grioni S., Kaaks R., Key T.J., Navarro C., Nilsson P.M., Overvad K., Palli D., Panico S., Quirós J., Rolandsson O., Sacerdote C., Sánchez M.J., Slimani N., Tjonneland A., Tumino R., van der A D.L., van der Schouw Y.T., Riboli E., Wareham N.J., Bowtell D.D., Green A., Chenevix-Trench G., deFazio A., Gertig D., Webb P.M., Brauch H., Justenhoven C., Hamann U., Ko Y.D., Baisch C., Fischer H.P., Pesch B., Rabstein S., Spickenheuer A., Harth V., Aghmesheh M., Amor D., Andrews L., Antill Y., Armitage S., Arnold L., Balleine R., Bankier A., Bastick P., Beesley J., Beilby J., Bennett I., Bennett B., Berry G., Blackburn A., Bogwitz M., Brennan M., Brown M., Buckley M., Burgess M., Burke J., Butow P., Byron K., Callen D., Campbell I., Chauhan D., Chenevix-Trench G., Christian A., Clarke C., Colley A., Cotton D., Crook A., Cui J., Culling B., Cummings M., Dawson S.J., deFazio A., Delatycki M., Dickson R., Dixon J., Dobrovic A., Dudding T., Edkins T., Edwards S., Eisenbruch M., Farshid G., Fawcett S., Fellows A., Fenton G., Field M., Firgaira F., Flanagan J., Fleming J., Fong P., Forbes J., Fox S., French J., Friedlander M., Gaff C., Gardner M., Gattas M., George P., Giles G., Gill G., Goldblatt J., Greening S., Grist S., Eric H., Hardie K., Harris M., Hart S., Hayward N., Healey S., Heiniger L., Hopper J., Humphrey E., Hunt C., James P., Jenkins M., Jones A., Kefford R., Kidd A., Kiely B., Kirk J., Koehler J., Kollias J., Kovalenko S., Lakhani S., Leaming A., Leary J., Lim J., Lindeman G., Lipton L., Lobb L., Mann G., Marsh D., McLachlan S.A., Meiser B., Meldrum C., Milne R., Mitchell G., Newman B., O'Connell S., O'Loughlin I., Osborne R., Pachter N., Patterson B., Peters L., Phillips K., Price M., Purser L., Reeve J., Reeve T., Richards R., Rickard E., Robinson B., Rudzki B., Saleh M., Salisbury E., Sambrook J., Saunders C., Saunus J., Sayer R., Scott E., Scott R., Scott C., Seshadri R., Sexton A., Sharma R., Shelling A., Simpson P., Southey M., Spurdle A., Suthers G., Sykes P., Taylor D., Taylor J., Thierry B., Thompson E., Thorne H., Townshend S., Trainer A., Tran L., Tucker K., Tyler J., Visvader J., Walker L., Walpole I., Waring P., Warner B., Warren G., Williams R., Wilson J., Winship I., Wu K., Young M.A.

ISSN

1476-4687 (Electronic)

ISSN-L

0028-0836

Publication state

Published

Issued date

02/10/2014

Peer-reviewed

Oui

Volume

514

Number

7520

Pages

92-97

Language

english

Notes

Publication types: Journal Article
Publication Status: ppublish

Abstract

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.

Keywords

Adolescent, Age Factors, Alleles, Body Mass Index, Breast Neoplasms/genetics, Cardiovascular Diseases/genetics, Child, Diabetes Mellitus, Type 2/genetics, Europe/ethnology, Female, Genetic Loci/genetics, Genome-Wide Association Study, Genomic Imprinting/genetics, Humans, Hypothalamo-Hypophyseal System/physiology, Intercellular Signaling Peptides and Proteins/genetics, Male, Membrane Proteins/genetics, Menarche/genetics, Obesity/genetics, Ovary/physiology, Parents, Polymorphism, Single Nucleotide/genetics, Potassium Channels, Tandem Pore Domain/genetics, Proteins/genetics, Quantitative Trait Loci/genetics, Receptors, GABA-B/metabolism, Receptors, Retinoic Acid/metabolism, Ribonucleoproteins/genetics

URN

urn:nbn:ch:serval-BIB_7816C9E4E3E58

OAI-PMH

oai:serval.unil.ch:BIB_7816C9E4E3E5

DOI

10.1038/nature13545

Pubmed

25231870

Create date

09/10/2014 16:12

Last modification date

18/01/2021 21:34

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

Details