Rare coding variants and X-linked loci associated with age at menarche
- Lunetta, Kathryn L.
- Day, Felix R.
- Sulem, Patrick
- Ruth, Katherine S.
- Tung, Joyce Y.
- Hinds, David A.
- Esko, Tõnu
- Elks, Cathy E.
- Altmaier, Elisabeth
- He, Chunyan
- Huffman, Jennifer E.
- Mihailov, Evelin
- Porcu, Eleonora
- Robino, Antonietta
- Rose, Lynda M.
- Schick, Ursula M.
- Stolk, Lisette
- Teumer, Alexander
- Thompson, Deborah J.
- Traglia, Michela
- Wang, Carol A.
- Yerges-Armstrong, Laura M.
- Antoniou, Antonis C.
- Barbieri, Caterina
- Coviello, Andrea D.
- Cucca, Francesco
- Demerath, Ellen W.
- Dunning, Alison M.
- Gandin, Ilaria
- Grove, Megan L.
- Gudbjartsson, Daniel F.
- Hocking, Lynne J.
- Hofman, Albert
- Huang, Jinyan
- Jackson, Rebecca D.
- Karasik, David
- Kriebel, Jennifer
- Lange, Ethan M.
- Lange, Leslie A.
- Langenberg, Claudia
- Li, Xin
- Luan, Jian'an
- Mägi, Reedik
- Morrison, Alanna C.
- Padmanabhan, Sandosh
- Pirie, Ailith
- Polasek, Ozren
- Porteous, David
- Reiner, Alex P.
- Rivadeneira, Fernando
- Rudan, Igor
- Sala, Cinzia F.
- Schlessinger, David
- Scott, Robert A.
- Stöckl, Doris
- Visser, Jenny A.
- Völker, Uwe
- Vozzi, Diego
- Wilson, James G.
- Zygmunt, Marek
- Boerwinkle, Eric
- Buring, Julie E.
- Crisponi, Laura
- Easton, Douglas F.
- Hayward, Caroline
- Hu, Frank B.
- Liu, Simin
- Metspalu, Andres
- Pennell, Craig E.
- Ridker, Paul M.
- Strauch, Konstantin
- Streeten, Elizabeth A.
- Toniolo, Daniela
- Uitterlinden, André G.
- Ulivi, Sheila
- Völzke, Henry
- Wareham, Nicholas J.
- Wellons, Melissa
- Franceschini, Nora
- Chasman, Daniel I.
- Thorsteinsdottir, Unnur
- Murray, Anna
- Stefansson, Kari
- Murabito, Joanne M.
- Ong, Ken K.
- Perry, John R. B.
DOIAbstract
More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ~3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08–4.6%; effect sizes 0.08–1.25 years per allele; P<5 × 10−8). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10−13) and FAAH2 (rs5914101, P=4.9 × 10−10). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide sig...
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