SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

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

Perry, JR; Day, F; Elks, CE; Sulem, P; Thompson, DJ; Ferreira, T; He, C; Chasman, DI; Esko, T; Thorleifsson, G; et al. Perry, JR; Day, F; Elks, CE; Sulem, P; Thompson, DJ; Ferreira, T; He, C; Chasman, DI; Esko, T; Thorleifsson, G; Albrecht, E; Ang, WQ; Corre, T; Cousminer, DL; Feenstra, B; Franceschini, N; Ganna, A; Johnson, AD; Kjellqvist, S; Lunetta, KL; McMahon, G; Nolte, IM; Paternoster, L; Porcu, E; Smith, AV; Stolk, L; Teumer, A; Tšernikova, N; Tikkanen, E; Ulivi, S; Wagner, EK; Amin, N; Bierut, LJ; Byrne, EM; Hottenga, JJ; Koller, DL; Mangino, M; Pers, TH; Yerges-Armstrong, LM; Hua Zhao, J; Andrulis, IL; Anton-Culver, H; Atsma, F; Bandinelli, S; Beckmann, MW; Benitez, J; Blomqvist, C; Bojesen, SE; Bolla, MK; Bonanni, B; Brauch, H; Brenner, H; Buring, JE; Chang-Claude, J; Chanock, S; Chen, J; Chenevix-Trench, G; Collée, JM; Couch, FJ; Couper, D; Coviello, AD; Cox, A; Czene, K; D'adamo, AP; Davey Smith, G; De Vivo, I; Demerath, EW; Dennis, J; Devilee, P; Dieffenbach, AK; Dunning, AM; Eiriksdottir, G; Eriksson, JG; Fasching, PA; Ferrucci, L; Flesch-Janys, D; Flyger, H; Foroud, T; Franke, L; Garcia, ME; García-Closas, M; Geller, F; de Geus, EE; Giles, GG; Gudbjartsson, DF; Gudnason, V; Guénel, P; Guo, S; Hall, P; Hamann, U; Haring, R; Hartman, CA; Heath, AC; Hofman, A; Hooning, MJ; Hopper, JL; Hu, FB; Hunter, DJ; Karasik, D; Kiel, DP; Knight, JA; Kosma, VM; Kutalik, Z; Lai, S; Lambrechts, D; Lindblom, A; Mägi, R; Magnusson, PK; Mannermaa, A; Martin, NG; Masson, G; McArdle, PF; McArdle, WL; Melbye, M; Michailidou, K; Mihailov, E; Milani, L; Milne, RL; Nevanlinna, H; Neven, P; Nohr, EA; Oldehinkel, AJ; Oostra, BA; Palotie, A; Peacock, M; Pedersen, NL; Peterlongo, P; Peto, J; Pharoah, PD; Postma, DS; Pouta, A; Pylkäs, K; Radice, P; Ring, S; Rivadeneira, F; Robino, A; Rose, LM; Rudolph, A; Salomaa, V; Sanna, S; Schlessinger, D; Schmidt, MK; Southey, MC; Sovio, U; Stampfer, MJ; Stöckl, D; Storniolo, AM; Timpson, NJ; Tyrer, J; Visser, JA; Vollenweider, P; Völzke, H; Waeber, G; Waldenberger, M; Wallaschofski, H; Wang, Q; Willemsen, G; Winqvist, R; Wolffenbuttel, BH; Wright, MJ; Australian Ovarian Cancer Study; GENICA Network; kConFab; LifeLines Cohort Study; InterAct Consortium; Early Growth Genetics (EGG) Consortium; Boomsma, DI; Econs, MJ; Khaw, KT; Loos, RJ; McCarthy, MI; Montgomery, GW; Rice, JP; Streeten, EA; Thorsteinsdottir, U; van Duijn, CM; Alizadeh, BZ; Bergmann, S; Boerwinkle, E; Boyd, HA; Crisponi, L; Gasparini, P; Gieger, C; Harris, TB; Ingelsson, E; Järvelin, MR; Kraft, P; Lawlor, D; Metspalu, A; Pennell, CE; Ridker, PM; Snieder, H; Sørensen, TI; Spector, TD; Strachan, DP; Uitterlinden, AG; Wareham, NJ; Widen, E; Zygmunt, M; Murray, A; Easton, DF; Stefansson, K; Murabito, JM; Ong, KK (2014) Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. Nature, 514 (7520). pp. 92-97. ISSN 1476-4687 https://doi.org/10.1038/nature13545
SGUL Authors: Strachan, David Peter

[img]
Preview
["document_typename_application/pdf; charset=binary" not defined] Accepted Version
Download (561kB) | Preview

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.

Item Type: Article
Additional Information: Author’s manuscript is made available for academic research only, and cannot be used for commercial purposes without prior permission of the copyright holders.
Keywords: Adolescent, Age Factors, Alleles, Body Mass Index, Breast Neoplasms, Cardiovascular Diseases, Child, Diabetes Mellitus, Type 2, Europe, Female, Genetic Loci, Genome-Wide Association Study, Genomic Imprinting, Humans, Hypothalamo-Hypophyseal System, Intercellular Signaling Peptides and Proteins, Male, Membrane Proteins, Menarche, Obesity, Ovary, Parents, Polymorphism, Single Nucleotide, Potassium Channels, Tandem Pore Domain, Proteins, Quantitative Trait Loci, Receptors, GABA-B, Receptors, Retinoic Acid, Ribonucleoproteins, General Science & Technology, MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Population Health Research Institute (INPH)
Journal or Publication Title: Nature
ISSN: 1476-4687
Language: eng
Dates:
DateEvent
2 October 2014Published
Projects:
Project IDFunderFunder ID
098381Wellcome TrustUNSPECIFIED
10118Cancer Research UKUNSPECIFIED
102215Wellcome TrustUNSPECIFIED
11022Cancer Research UKUNSPECIFIED
14136Cancer Research UKUNSPECIFIED
16561Cancer Research UKUNSPECIFIED
16563Cancer Research UKUNSPECIFIED
G0701863Medical Research CouncilUNSPECIFIED
G1000143Medical Research CouncilUNSPECIFIED
G9815508Medical Research CouncilUNSPECIFIED
MC_U106179471Medical Research CouncilUNSPECIFIED
MC_U106179472Medical Research CouncilUNSPECIFIED
MC_UU_12013/1Medical Research CouncilUNSPECIFIED
MC_UU_12013/3Medical Research CouncilUNSPECIFIED
MC_UU_12015/1Medical Research CouncilUNSPECIFIED
MC_UU_12015/2Medical Research CouncilUNSPECIFIED
MR/J012165/1Medical Research CouncilUNSPECIFIED
NF-SI-0512-10114Department of HealthUNSPECIFIED
NF-SI-0512-10135Department of HealthUNSPECIFIED
R01 AG041517NIA NIH HHSUNSPECIFIED
PubMed ID: 25231870
Web of Science ID: WOS:000342420800042
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107384
Publisher's version: https://doi.org/10.1038/nature13545

Actions (login required)

Edit Item Edit Item