Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.
Elks CE., Perry JRB., Sulem P., Chasman DI., Franceschini N., He C., Lunetta KL., Visser JA., Byrne EM., Cousminer DL., Gudbjartsson DF., Esko T., Feenstra B., Hottenga J-J., Koller DL., Kutalik Z., Lin P., Mangino M., Marongiu M., McArdle PF., Smith AV., Stolk L., van Wingerden SH., Zhao JH., Albrecht E., Corre T., Ingelsson E., Hayward C., Magnusson PKE., Smith EN., Ulivi S., Warrington NM., Zgaga L., Alavere H., Amin N., Aspelund T., Bandinelli S., Barroso I., Berenson GS., Bergmann S., Blackburn H., Boerwinkle E., Buring JE., Busonero F., Campbell H., Chanock SJ., Chen W., Cornelis MC., Couper D., Coviello AD., d'Adamo P., de Faire U., de Geus EJC., Deloukas P., Döring A., Smith GD., Easton DF., Eiriksdottir G., Emilsson V., Eriksson J., Ferrucci L., Folsom AR., Foroud T., Garcia M., Gasparini P., Geller F., Gieger C., GIANT Consortium None., Gudnason V., Hall P., Hankinson SE., Ferreli L., Heath AC., Hernandez DG., Hofman A., Hu FB., Illig T., Järvelin M-R., Johnson AD., Karasik D., Khaw K-T., Kiel DP., Kilpeläinen TO., Kolcic I., Kraft P., Launer LJ., Laven JSE., Li S., Liu J., Levy D., Martin NG., McArdle WL., Melbye M., Mooser V., Murray JC., Murray SS., Nalls MA., Navarro P., Nelis M., Ness AR., Northstone K., Oostra BA., Peacock M., Palmer LJ., Palotie A., Paré G., Parker AN., Pedersen NL., Peltonen L., Pennell CE., Pharoah P., Polasek O., Plump AS., Pouta A., Porcu E., Rafnar T., Rice JP., Ring SM., Rivadeneira F., Rudan I., Sala C., Salomaa V., Sanna S., Schlessinger D., Schork NJ., Scuteri A., Segrè AV., Shuldiner AR., Soranzo N., Sovio U., Srinivasan SR., Strachan DP., Tammesoo M-L., Tikkanen E., Toniolo D., Tsui K., Tryggvadottir L., Tyrer J., Uda M., van Dam RM., van Meurs JBJ., Vollenweider P., Waeber G., Wareham NJ., Waterworth DM., Weedon MN., Wichmann HE., Willemsen G., Wilson JF., Wright AF., Young L., Zhai G., Zhuang WV., Bierut LJ., Boomsma DI., Boyd HA., Crisponi L., Demerath EW., van Duijn CM., Econs MJ., Harris TB., Hunter DJ., Loos RJF., Metspalu A., Montgomery GW., Ridker PM., Spector TD., Streeten EA., Stefansson K., Thorsteinsdottir U., Uitterlinden AG., Widen E., Murabito JM., Ong KK., Murray A.
To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.