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Rare coding variants and X-linked loci associated with age at menarche

Lunetta, Kathryn L. (author)
Day, Felix R. (author)
Sulem, Patrick (author)
show more...
Ruth, Katherine S. (author)
Tung, Joyce Y. (author)
Hinds, David A. (author)
Esko, Tonu (author)
Elks, Cathy E. (author)
Altmaier, Elisabeth (author)
He, Chunyan (author)
Huffman, Jennifer E. (author)
Mihailov, Evelin (author)
Porcu, Eleonora (author)
Robino, Antonietta (author)
Rose, Lynda M. (author)
Schick, Ursula M. (author)
Stolk, Lisette (author)
Teumer, Alexander (author)
Thompson, Deborah J. (author)
Traglia, Michela (author)
Wang, Carol A. (author)
Yerges-Armstrong, Laura M. (author)
Antoniou, Antonis C. (author)
Barbieri, Caterina (author)
Coviello, Andrea D. (author)
Cucca, Francesco (author)
Demerath, Ellen W. (author)
Dunning, Alison M. (author)
Gandin, Ilaria (author)
Grove, Megan L. (author)
Gudbjartsson, Daniel F. (author)
Hocking, Lynne J. (author)
Hofman, Albert (author)
Huang, Jinyan (author)
Jackson, Rebecca D. (author)
Karasik, David (author)
Kriebel, Jennifer (author)
Lange, Ethan M. (author)
Lange, Leslie A. (author)
Langenberg, Claudia (author)
Li, Xin (author)
Luan, Jian'an (author)
Maegi, Reedik (author)
Morrison, Alanna C. (author)
Padmanabhan, Sandosh (author)
Pirie, Ailith (author)
Polasek, Ozren (author)
Porteous, David (author)
Reiner, Alex P. (author)
Rivadeneira, Fernando (author)
Rudan, Igor (author)
Sala, Cinzia F. (author)
Schlessinger, David (author)
Scott, Robert A. (author)
Stoeckl, Doris (author)
Visser, Jenny A. (author)
Voelker, Uwe (author)
Vozzi, Diego (author)
Wilson, James G. (author)
Zygmunt, Marek (author)
Boerwinkle, Eric (author)
Buring, Julie E. (author)
Crisponi, Laura (author)
Easton, Douglas F. (author)
Hayward, Caroline (author)
Hu, Frank B. (author)
Liu, Simin (author)
Metspalu, Andres (author)
Pennell, Craig E. (author)
Ridker, Paul M. (author)
Strauch, Konstantin (author)
Streeten, Elizabeth A. (author)
Toniolo, Daniela (author)
Uitterlinden, Andre G. (author)
Ulivi, Sheila (author)
Voelzke, Henry (author)
Wareham, Nicholas J. (author)
Wellons, Melissa (author)
Franceschini, Nora (author)
Chasman, Daniel I. (author)
Thorsteinsdottir, Unnur (author)
Murray, Anna (author)
Stefansson, Kari (author)
Murabito, Joanne M. (author)
Ong, Ken K. (author)
Perry, John R. B. (author)
Forouhi, Nita G. (author)
Kerrison, Nicola D. (author)
Sharp, Stephen J. (author)
Sims, Matt (author)
Barroso, Ines (author)
Deloukas, Panos (author)
McCarthy, Mark I. (author)
Arriola, Larraitz (author)
Balkau, Beverley (author)
Barricarte, Aurelio (author)
Boeing, Heiner (author)
Franks, Paul W. (author)
Gonzalez, Carlos (author)
Grioni, Sara (author)
Kaaks, Rudolf (author)
Key, Timothy J. (author)
Navarro, Carmen (author)
Nilsson, Peter M. (author)
Overvad, Kim (author)
Palli, Domenico (author)
Panico, Salvatore (author)
Ramon Quiros, J. (author)
Rolandsson, Olov (author)
Sacerdote, Carlotta (author)
Sanchez, Maria-Jose (author)
Slimani, Nadia (author)
Tjonneland, Anne (author)
Tumino, Rosario (author)
van der A, Daphne L. (author)
van der Schouw, Yvonne T. (author)
Riboli, Elio (author)
Smith, Blair H. (author)
Campbell, Archie (author)
Deary, Ian J. (author)
McIntosh, Andrew M. (author)
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 (publisher)
 (publisher)
2015
2015
English.
In: Nature Communications. - 2041-1723. ; 6
  • swepub:Mat__t
Abstract Subject headings
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  • More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding 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 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.

Subject headings

Medical and Health Sciences  (hsv)
Basic Medicine  (hsv)
Medical Genetics  (hsv)
Medicin och hälsovetenskap  (hsv)
Medicinska grundvetenskaper  (hsv)
Medicinsk genetik  (hsv)

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By the author/editor
Lunetta, Kathryn ...
Day, Felix R.
Sulem, Patrick
Ruth, Katherine ...
Tung, Joyce Y.
Hinds, David A.
show more...
Esko, Tonu
Elks, Cathy E.
Altmaier, Elisab ...
He, Chunyan
Huffman, Jennife ...
Mihailov, Evelin
Porcu, Eleonora
Robino, Antoniet ...
Rose, Lynda M.
Schick, Ursula M ...
Stolk, Lisette
Teumer, Alexande ...
Thompson, Debora ...
Traglia, Michela
Wang, Carol A.
Yerges-Armstrong ...
Antoniou, Antoni ...
Barbieri, Cateri ...
Coviello, Andrea ...
Cucca, Francesco
Demerath, Ellen ...
Dunning, Alison ...
Gandin, Ilaria
Grove, Megan L.
Gudbjartsson, Da ...
Hocking, Lynne J ...
Hofman, Albert
Huang, Jinyan
Jackson, Rebecca ...
Karasik, David
Kriebel, Jennife ...
Lange, Ethan M.
Lange, Leslie A.
Langenberg, Clau ...
Li, Xin
Luan, Jian'an
Maegi, Reedik
Morrison, Alanna ...
Padmanabhan, San ...
Pirie, Ailith
Polasek, Ozren
Porteous, David
Reiner, Alex P.
Rivadeneira, Fer ...
Rudan, Igor
Sala, Cinzia F.
Schlessinger, Da ...
Scott, Robert A.
Stoeckl, Doris
Visser, Jenny A.
Voelker, Uwe
Vozzi, Diego
Wilson, James G.
Zygmunt, Marek
Boerwinkle, Eric
Buring, Julie E.
Crisponi, Laura
Easton, Douglas ...
Hayward, Carolin ...
Hu, Frank B.
Liu, Simin
Metspalu, Andres
Pennell, Craig E ...
Ridker, Paul M.
Strauch, Konstan ...
Streeten, Elizab ...
Toniolo, Daniela
Uitterlinden, An ...
Ulivi, Sheila
Voelzke, Henry
Wareham, Nichola ...
Wellons, Melissa
Franceschini, No ...
Chasman, Daniel ...
Thorsteinsdottir ...
Murray, Anna
Stefansson, Kari
Murabito, Joanne ...
Ong, Ken K.
Perry, John R. B ...
Forouhi, Nita G.
Kerrison, Nicola ...
Sharp, Stephen J ...
Sims, Matt
Barroso, Ines
Deloukas, Panos
McCarthy, Mark I ...
Arriola, Larrait ...
Balkau, Beverley
Barricarte, Aure ...
Boeing, Heiner
Franks, Paul W.
Gonzalez, Carlos
Grioni, Sara
Kaaks, Rudolf
Key, Timothy J.
Navarro, Carmen
Nilsson, Peter M ...
Overvad, Kim
Palli, Domenico
Panico, Salvator ...
Ramon Quiros, J.
Rolandsson, Olov
Sacerdote, Carlo ...
Sanchez, Maria-J ...
Slimani, Nadia
Tjonneland, Anne
Tumino, Rosario
van der A, Daphn ...
van der Schouw, ...
Riboli, Elio
Smith, Blair H.
Campbell, Archie
Deary, Ian J.
McIntosh, Andrew ...
show less...
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