Rare coding variants and X-linked loci associated with age at menarche
Lunetta, Kathryn L. (Boston University School of Public Health (Estats Units d'Amèrica))
Day, Felix R. (University of Cambridge. School of Clinical Medicine (Gran Bretanya))
Sulem, Patrick (deCODE Genetics (Reykjavík, Islàndia))
Ruth, Katherine S. (University of Exeter. Medical School (Gran Bretanya))
Tung, Joyce Y. (23andMe (California, Estats Units d'Amèrica))
Hinds, David A. (23andMe (California, Estats Units d'Amèrica))
Esko, Tõnu (University of Tartu. Estonian Genome Center (Estònia))
Elks, Cathy E. (University of Cambridge. School of Clinical Medicine (Gran Bretanya))
Altmaier, Elisabeth (Helmholtz Zentrum München (Alemanya))
He, Chunyan (Fairbanks School of Public Health (Indianapolis, Estats Units d'Amèrica))
Huffman, Jennifer E. (University of Edinburgh. Institute of Genetics and Molecular Medicine (Gran Bretanya))
Mihailov, Evelin (University of Tartu. Estonian Genome Center (Estònia))
Porcu, Eleonora (Institute of Genetics and Biomedical Research (Sardinia, Itàlia))
Robino, Antonietta (Institute for Maternal and Child Health (Trieste, Itàlia))
Rose, Lynda M. (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Schick, Ursula M. (Fred Hutchinson Cancer Research Center (Seattle, Estats Units d'Amèrica))
Stolk, Lisette (Erasmus University Rotterdam)
Teumer, Alexander (University Medicine Greifswald (Alemanya))
Thompson, Deborah J. (University of Cambridge. Centre for Cancer Genetic Epidemiology)
Traglia, Michela (San Raffaele Scientific Institute (Milà, Itàlia))
Wang, Carol A. (University of Western Australia. School of Women's and Infants' Health (Crawley, Austràlia))
Yerges-Armstrong, Laura M. (University of Maryland School of Medicine (Estats Units d'Amèrica))
Antoniou, Antonis C. (University of Cambridge. Centre for Cancer Genetic Epidemiology)
Barbieri, Caterina (San Raffaele Scientific Institute (Milà, Itàlia))
Coviello, Andrea D. (Boston University School of Medicine (Estats Units d'Amèrica))
Cucca, Francesco (Institute of Genetics and Biomedical Research (Sardinia, Itàlia))
Demerath, Ellen W. (University of Minnesota (Minneapolis, Estats Units d'Amèrica))
Dunning, Alison M. (University of Cambridge. Centre for Cancer Genetic Epidemiology)
Gandin, Ilaria (Institute for Maternal and Child Health (Trieste, Itàlia))
Grove, Megan L. (University of Texas Health Science Center at Houston (Estats Units d'Amèrica))
Gudbjartsson, Daniel F. (deCODE Genetics (Reykjavík, Islàndia))
Hocking, Lynne J. (University of Aberdeen (Regne Unit))
Hofman, Albert (Erasmus MC (Rotterdam, Paisos Baixos))
Huang, Jinyan (Shanghai Jiao Tong University School of Medicine)
Jackson, Rebecca D. (The Ohio State University (Estats Units d'Amèrica))
Karasik, David (Harvard Medical School (Boston, Estats Units d'Amèrica))
Kriebel, Jennifer (Helmholtz Zentrum München (Alemanya))
Lange, Ethan M. (University of North Carolina. Department of Genetics (Estats Units d'Amèrica))
Lange, Leslie A. (University of North Carolina. Department of Genetics (Estats Units d'Amèrica))
Langenberg, Claudia (University of Cambridge. School of Clinical Medicine (Gran Bretanya))
Li, Xin (Harvard T.H. Chan School of Public Health (Boston, Estats Units d'Amèrica))
Luan, Jian'an (University of Cambridge. School of Clinical Medicine (Gran Bretanya))
Mägi, Reedik (University of Tartu. Estonian Genome Center (Estònia))
Morrison, Alanna (University of Texas Health Science Center at Houston (Estats Units d'Amèrica))
Padmanabhan, Sandosh (University of Glasgow. Institute of Cardiovascular and Medical Sciences (Gran Bretanya))
Pirie, Ailith (University of Cambridge. Centre for Cancer Genetic Epidemiology)
Polasek, Ozren (University of Split. School of Medicine (Croàcia))
Porteous, David (University of Edinburgh.Institute of Genetics and Molecular Medicine (Gran Bretanya))
Reiner, Alex P. (Fred Hutchinson Cancer Research Center (Seattle, Estats Units d'Amèrica))
Rivadeneira, Fernando (Erasmus University Rotterdam)
Rudan, Igor (University of Edinburgh. Institute for Population Health Sciences and Informatics (Gran Bretanya))
Sala, Cinzia F. (San Raffaele Scientific Institute (Milà, Itàlia))
Schlessinger, David (National Institute on Aging (Baltimore, Estats Units d'Amèrica))
Scott, Robert A. (University of Cambridge. School of Clinical Medicine (Gran Bretanya))
Stöckl, Doris (German Research Center for Environmental Health (Germany))
Visser, J. (Erasmus University Rotterdam)
Völker, Uwe (Greifswald Medical School (Alemanya))
Vozzi, Diego (Institute for Maternal and Child Health (Trieste, Itàlia))
Wilson, James G. (University of Mississippi. Department of Physiology and Biophysics (Estats Units d'Amèrica))
Zygmunt, Marek (Greifswald Medical School (Alemanya))
Boerwinkle, Eric (University of Texas Health Science Center at Houston (Estats Units d'Amèrica))
Buring, Julie (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Crisponi, Laura (Institute of Genetics and Biomedical Research (Sardinia, Itàlia))
Easton, Douglas F. (University of Cambridge. Centre for Cancer Genetic Epidemiology)
Hayward, Caroline (University of Edinburgh. Institute of Genetics and Molecular Medicine (Gran Bretanya))
Hu, Frank B. (Harvard Medical School (Boston, Estats Units d'Amèrica))
Liu, Simin (Brown University. Departments of Epidemiology and Medicine (Providence, Estats Units d'Amèrica))
Metspalu, Andres (University of Tartu. Estonian Genome Center (Estònia))
Pennell, Craig E. (University of Western Australia. School of Women's and Infants' Health (Crawley, Austràlia))
Ridker, Paul M. (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Strauch, Konstantin (German Research Center for Environmental Health (Germany))
Streeten, Elizabeth A. (University of Maryland School of Medicine (Estats Units d'Amèrica))
Toniolo, Daniela (San Raffaele Scientific Institute (Milà, Itàlia))
Uitterlinden, André G. (Erasmus University Rotterdam)
Ulivi, Sheila (Institute for Maternal and Child Health (Trieste, Itàlia))
Völzke, Henry (University Medicine Greifswald (Alemanya))
Wareham, Nicholas J. (University of Cambridge. School of Clinical Medicine (Gran Bretanya))
Wellons, Melissa (Vanderbilt University Medical Center (Nashville, Estats Units d'Amèrica))
Franceschini, Nora (University of North Carolina (Estats Units d'Amèrica). Department of Epidemiology)
Chasman, Daniel I. (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Thorsteinsdottir, Unnur (deCODE Genetics (Reykjavík, Islàndia))
Murray, Anna (University of Exeter. Medical School (Gran Bretanya))
Stefánsson, Kári (deCODE Genetics (Reykjavík, Islàndia))
Murabito, Joanne M. (National Heart, Lung, and Blood Institute (Framingham, Estats Units d'Amèrica))
Ong, Ken K. (University of Cambridge. School of Clinical Medicine (Gran Bretanya))
Perry, John R. B. (University of Cambridge. School of Clinical Medicine (Gran Bretanya))

Date:	2015
Abstract:	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 signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p. W275X) is associated with 1. 25-year-later menarche (P=2. 8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0. 5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
Note:	Ha col·laborat en aquest article l'investigador Carlos González (Institut Germans Trias i Pujol. Institut Català d'Oncologia)
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Genètica ; Menstruació
Published in:	Nature communications, Vol. 4 Núm. 6 (august 2015) , ISSN 2041-1723

DOI: 10.1038/ncomms8756
PMID: 26239645

7 p, 299.7 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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