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

Perry, John R. B., Day, Felix, Elks, Cathy E., Sulem, Patrick, Thompson, Deborah J., Ferreira, Teresa, He, Chunyan, Chasman, Daniel I., Esko, Toenu, Thorleifsson, Gudmar, Albrecht, Eva, Ang, Wei Q., Corre, Tanguy, Cousminer, Diana L., Feenstra, Bjarke, Franceschini, Nora, Ganna, Andrea, Johnson, Andrew D., Kjellqvist, Sanela, Lunetta, Kathryn L., McMahon, George, Nolte, Ilja M., Paternoster, Lavinia, Porcu, Eleonora, Smith, Albert V., Stolk, Lisette, Teumer, Alexander, Tsernikova, Natalia, Tikkanen, Emmi, Ulivi, Sheila, Wagner, Erin K., Amin, Najaf, Bierut, Laura J., Byrne, Enda M., Hottenga, Jouke-Jan, Koller, Daniel L., Mangino, Massimo, Pers, Tune H., Yerges-Armstrong, Laura M., Zhao, Jing Hua, Andrulis, Irene L., Anton-Culver, Hoda, Atsma, Femke, Bandinelli, Stefania, Beckmann, Matthias W., Benitez, Javier, Blomqvist, Carl, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Buring, Julie E., Chang-Claude, Jenny, Chanock, Stephen, Chen, Jinhui, Chenevix-Trench, Georgia, Collee, J. Margriet, Couch, Fergus J., Couper, David, Coviello, Andrea D., Cox, Angela, Czene, Kamila, D'adamo, Adamo Pio, Smith, George Davey, De Vivo, Immaculata, Demerath, Ellen W., Dennis, Joe, Devilee, Peter, Dieffenbach, Aida K., Dunning, Alison M., Eiriksdottir, Gudny, Eriksson, Johan G., Fasching, Peter A., Ferrucci, Luigi, Flesch-Janys, Dieter, Flyger, Henrik, Foroud, Tatiana, Franke, Lude, Garcia, Melissa E., Garcia-Closas, Montserrat, Geller, Frank, de Geus, Eco E. J., Giles, Graham G., Gudbjartsson, Daniel F., Gudnason, Vilmundur, Guenel, Pascal, Guo, Suiqun, Hall, Per, Hamann, Ute, Haring, Robin, Hartman, Catharina A., Heath, AndrewC., Hofman, Albert, Hooning, Maartje J., Hopper, John L., Hu, Frank B., Hunter, David J., Karasik, David, Kiel, Douglas P., Knight, Julia A., Kosma, Veli-Matti, Kutalik, Zoltan, Lai, Sandra, Lambrechts, Diether, Lindblom, Annika, Maegi, Reedik, Magnusson, Patrik K., Mannermaa, Arto, Martin, Nicholas G., Masson, Gisli, McArdle, Patrick F., McArdle, Wendy L., Melbye, Mads, Michailidou, Kyriaki, Mihailov, Evelin, Milani, Lili, Milne, Roger L., Nevanlinna, Heli, Neven, Patrick, Nohr, Ellen A., Oldehinkel, Albertine J., Oostra, Ben A., Palotie, Aarno, Peacock, Munro, Pedersen, Nancy L., Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Postma, Dirkje S., Pouta, Anneli, Pylkaes, Katri, Radice, Paolo, Ring, Susan, Rivadeneira, Fernando, Robino, Antonietta, Rose, Lynda M., Rudolph, Anja, Salomaa, Veikko, Sanna, Serena, Schlessinger, David, Schmidt, Marjanka K., Southey, Mellissa C., Sovio, Ulla, Stampfer, Meir J., Stoeckl, Doris, Storniolo, Anna M., Timpson, Nicholas J., Tyrer, Jonathan, Visser, Jenny A., Vollenweider, Peter, Voelzke, Henry, Waeber, Gerard, Waldenberger, Melanie, Wallaschofski, Henri, Wang, Qin, Willemsen, Gonneke, Winqvist, Robert, Wolffenbuttel, Bruce H. R., Wright, Margaret J., Australian Ovarian Cancer Study, The GENICA Network, kConFab, The LifeLines Cohort Study, The InterAct Consortium, Early Growth Genetics (EGG) Consortium, Boomsma, Dorret I., Econs, Michael J., Khaw, Kay-Tee, Loos, Ruth J. F., McCarthy, Mark I., Montgomery, Grant W., Rice, John P., Streeten, Elizabeth A., Thorsteinsdottir, Unnur, van Duijn, Cornelia M., Alizadeh, Behrooz Z., Bergmann, Sven, Boerwinkle, Eric, Boyd, Heather A., Crisponi, Laura, Gasparini, Paolo, Gieger, Christian, Harris, Tamara B., Ingelsson, Erik, Jaervelin, Marjo-Riitta, Kraft, Peter, Lawlor, Debbie, Metspalu, Andres, Pennell, Craig E., Ridker, Paul M., Snieder, Harold, Sorensen, Thorkild I. A., Spector, Tim D., Strachan, David P., Uitterlinden, Andre G., Wareham, Nicholas J., Widen, Elisabeth, Zygmunt, Marek, Murray, Anna, Easton, Douglas F., Stefansson, Kari, Murabito, Joanne M., Ong, Ken K., the ReproGen Consortium and Middeldorp, Christel (2014) Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. Nature, 514 7520: 92-97. doi:10.1038/nature13545

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Author Perry, John R. B.
Day, Felix
Elks, Cathy E.
Sulem, Patrick
Thompson, Deborah J.
Ferreira, Teresa
He, Chunyan
Chasman, Daniel I.
Esko, Toenu
Thorleifsson, Gudmar
Albrecht, Eva
Ang, Wei Q.
Corre, Tanguy
Cousminer, Diana L.
Feenstra, Bjarke
Franceschini, Nora
Ganna, Andrea
Johnson, Andrew D.
Kjellqvist, Sanela
Lunetta, Kathryn L.
McMahon, George
Nolte, Ilja M.
Paternoster, Lavinia
Porcu, Eleonora
Smith, Albert V.
Stolk, Lisette
Teumer, Alexander
Tsernikova, Natalia
Tikkanen, Emmi
Ulivi, Sheila
Wagner, Erin K.
Amin, Najaf
Bierut, Laura J.
Byrne, Enda M.
Hottenga, Jouke-Jan
Koller, Daniel L.
Mangino, Massimo
Pers, Tune H.
Yerges-Armstrong, Laura M.
Zhao, Jing Hua
Andrulis, Irene L.
Anton-Culver, Hoda
Atsma, Femke
Bandinelli, Stefania
Beckmann, Matthias W.
Benitez, Javier
Blomqvist, Carl
Bojesen, Stig E.
Bolla, Manjeet K.
Bonanni, Bernardo
Brauch, Hiltrud
Brenner, Hermann
Buring, Julie E.
Chang-Claude, Jenny
Chanock, Stephen
Chen, Jinhui
Chenevix-Trench, Georgia
Collee, J. Margriet
Couch, Fergus J.
Couper, David
Coviello, Andrea D.
Cox, Angela
Czene, Kamila
D'adamo, Adamo Pio
Smith, George Davey
De Vivo, Immaculata
Demerath, Ellen W.
Dennis, Joe
Devilee, Peter
Dieffenbach, Aida K.
Dunning, Alison M.
Eiriksdottir, Gudny
Eriksson, Johan G.
Fasching, Peter A.
Ferrucci, Luigi
Flesch-Janys, Dieter
Flyger, Henrik
Foroud, Tatiana
Franke, Lude
Garcia, Melissa E.
Garcia-Closas, Montserrat
Geller, Frank
de Geus, Eco E. J.
Giles, Graham G.
Gudbjartsson, Daniel F.
Gudnason, Vilmundur
Guenel, Pascal
Guo, Suiqun
Hall, Per
Hamann, Ute
Haring, Robin
Hartman, Catharina A.
Heath, AndrewC.
Hofman, Albert
Hooning, Maartje J.
Hopper, John L.
Hu, Frank B.
Hunter, David J.
Karasik, David
Kiel, Douglas P.
Knight, Julia A.
Kosma, Veli-Matti
Kutalik, Zoltan
Lai, Sandra
Lambrechts, Diether
Lindblom, Annika
Maegi, Reedik
Magnusson, Patrik K.
Mannermaa, Arto
Martin, Nicholas G.
Masson, Gisli
McArdle, Patrick F.
McArdle, Wendy L.
Melbye, Mads
Michailidou, Kyriaki
Mihailov, Evelin
Milani, Lili
Milne, Roger L.
Nevanlinna, Heli
Neven, Patrick
Nohr, Ellen A.
Oldehinkel, Albertine J.
Oostra, Ben A.
Palotie, Aarno
Peacock, Munro
Pedersen, Nancy L.
Peterlongo, Paolo
Peto, Julian
Pharoah, Paul D. P.
Postma, Dirkje S.
Pouta, Anneli
Pylkaes, Katri
Radice, Paolo
Ring, Susan
Rivadeneira, Fernando
Robino, Antonietta
Rose, Lynda M.
Rudolph, Anja
Salomaa, Veikko
Sanna, Serena
Schlessinger, David
Schmidt, Marjanka K.
Southey, Mellissa C.
Sovio, Ulla
Stampfer, Meir J.
Stoeckl, Doris
Storniolo, Anna M.
Timpson, Nicholas J.
Tyrer, Jonathan
Visser, Jenny A.
Vollenweider, Peter
Voelzke, Henry
Waeber, Gerard
Waldenberger, Melanie
Wallaschofski, Henri
Wang, Qin
Willemsen, Gonneke
Winqvist, Robert
Wolffenbuttel, Bruce H. R.
Wright, Margaret J.
Australian Ovarian Cancer Study
The GENICA Network
kConFab
The LifeLines Cohort Study
The InterAct Consortium
Early Growth Genetics (EGG) Consortium
Boomsma, Dorret I.
Econs, Michael J.
Khaw, Kay-Tee
Loos, Ruth J. F.
McCarthy, Mark I.
Montgomery, Grant W.
Rice, John P.
Streeten, Elizabeth A.
Thorsteinsdottir, Unnur
van Duijn, Cornelia M.
Alizadeh, Behrooz Z.
Bergmann, Sven
Boerwinkle, Eric
Boyd, Heather A.
Crisponi, Laura
Gasparini, Paolo
Gieger, Christian
Harris, Tamara B.
Ingelsson, Erik
Jaervelin, Marjo-Riitta
Kraft, Peter
Lawlor, Debbie
Metspalu, Andres
Pennell, Craig E.
Ridker, Paul M.
Snieder, Harold
Sorensen, Thorkild I. A.
Spector, Tim D.
Strachan, David P.
Uitterlinden, Andre G.
Wareham, Nicholas J.
Widen, Elisabeth
Zygmunt, Marek
Murray, Anna
Easton, Douglas F.
Stefansson, Kari
Murabito, Joanne M.
Ong, Ken K.
the ReproGen Consortium
Middeldorp, Christel
Title Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
1476-4687
Publication date 2014-10-01
Year available 2014
Sub-type Article (original research)
DOI 10.1038/nature13545
Open Access Status Not yet assessed
Volume 514
Issue 7520
Start page 92
End page 97
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing
Language eng
Subject 1000 General
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.
Keyword Central Precocious Puberty
Human Prefrontal Cortex
Breast-Cancer Risk
Gene-Expression
Wide Association
Metaanalysis
Disease
Variants
Cells
Reveals
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID R01 NS017950
MC_UU_12013/3
G1000143
MR/J012165/1
R01 AG041517
UL1 TR001108
102215
MC_UU_12015/1
MC_U106179471
MC_UU_12015/2
MC_PC_15018
MC_U106179472
P50 CA116201
G0401527
MC_UU_12013/1
G0701863
098381
10118
G9815508
10124
U01 AG049505
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 121 times in Thomson Reuters Web of Science Article | Citations
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