Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

Cathy E. Elks; John R B Perry; Patrick Sulem; Daniel I. Chasman; Nora Franceschini; Chunyan He; Kathryn L. Lunetta; Jenny A. Visser; Enda M. Byrne; Diana L. Cousminer; Daniel F. Gudbjartsson; Tõnu Esko; Bjarke Feenstra; Jouke Jan Hottenga; Daniel L. Koller; Zoltán Kutalik; Peng Lin; Massimo Mangino; Mara Marongiu; Patrick F. McArdle; Albert V. Smith; Lisette Stolk; Sophie H. Van Wingerden; Jing Hua Zhao; Eva Albrecht; Tanguy Corre; Erik Ingelsson; Caroline Hayward; Patrik K E Magnusson; Erin N. Smith; Shelia Ulivi; Nicole M. Warrington; Lina Zgaga; Helen Alavere; Najaf Amin; Thor Aspelund; Stefania Bandinelli; Inês Barroso; Gerald S. Berenson; Sven Bergmann; Hannah Blackburn; Eric Boerwinkle; Julie E. Buring; Fabio Busonero; Harry Campbell; Stephen J. Chanock; Wei Chen; Marilyn C. Cornelis; David Couper; Andrea D. Coviello; Pio D'Adamo; Ulf De Faire; Eco J C De Geus; Panos Deloukas; Angela Döring; George Davey Smith; Douglas F. Easton; Gudny Eiriksdottir; Valur Emilsson; Johan Eriksson; Luigi Ferrucci; Aaron R. Folsom; Tatiana Foroud; Melissa Garcia; Paolo Gasparini; Frank Geller; Christian Gieger; Vilmundur Gudnason; Per Hall; Susan E. Hankinson; Liana Ferreli; Andrew C. Heath; Dena G. Hernandez; Albert Hofman; Frank B. Hu; Thomas Illig; Marjo Riitta Järvelin; Andrew D. Johnson; David Karasik; Kay Tee Khaw; Douglas P. Kiel; Tuomas O. Kilpelänen; Ivana Kolcic; Peter Kraft; Lenore J. Launer; Joop S E Laven; Shengxu Li; Jianjun Liu; Daniel Levy; Nicholas G. Martin; Wendy L. McArdle; Mads Melbye; Vincent Mooser; Jeffrey C. Murray; Sarah S. Murray; Michael A. Nalls; Pau Navarro; Mari Nelis; Andrew R. Ness; Kate Northstone; Ben A. Oostra; Munro Peacock; Lyle J. Palmer; Aarno Palotie; Guillaume Paré; Alex N. Parker; Nancy L. Pedersen; Leena Peltonen; Craig E. Pennell; Paul Pharoah; Ozren Polasek; Andrew S. Plump; Anneli Pouta; Eleonora Porcu; Thorunn Rafnar; John P. Rice; Susan M. Ring; Fernando Rivadeneira; Igor Rudan; Cinzia Sala; Veikko Salomaa; Serena Sanna; David Schlessinger; Nicholas J. Schork; Angelo Scuteri; Ayellet V. Segrè; Alan R. Shuldiner; Nicole Soranzo; Ulla Sovio; Sathanur R. Srinivasan; David P. Strachan; Mar Liis Tammesoo; Emmi Tikkanen; Daniela Toniolo; Kim Tsui; Laufey Tryggvadottir; Jonathon Tyrer; Manuela Uda; Rob M. Van Dam; Joyce B J Van Meurs; Peter Vollenweider; Gerard Waeber; Nicholas J. Wareham; Dawn M. Waterworth; Michael N. Weedon; H. Erich Wichmann; Gonneke Willemsen; James F. Wilson; Alan F. Wright; Lauren Young; Guangju Zhai; Wei Vivian Zhuang; Laura J. Bierut; Dorret I. Boomsma; Heather A. Boyd; Laura Crisponi; Ellen W. Demerath; Cornelia M. Van Duijn; Michael J. Econs; Tamara B. Harris; David J. Hunter; Ruth J F Loos; Andres Metspalu; Grant W. Montgomery; Paul M. Ridker; Tim D. Spector; Elizabeth A. Streeten; Kari Stefansson; Unnur Thorsteinsdottir; André G. Uitterlinden; Elisabeth Widen; Joanne M. Murabito; Ken K. Ong; Anna Murray

doi:10.1038/ng.714

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

Cathy E. Elks, John R B Perry, Patrick Sulem, Daniel I. Chasman, Nora Franceschini, Chunyan He, Kathryn L. Lunetta, Jenny A. Visser, Enda M. Byrne, Diana L. Cousminer, Daniel F. Gudbjartsson, Tõnu Esko, Bjarke Feenstra, Jouke Jan Hottenga, Daniel L. Koller, Zoltán Kutalik, Peng Lin, Massimo Mangino, Mara Marongiu, Patrick F. McArdleAlbert V. Smith, Lisette Stolk, Sophie H. Van Wingerden, Jing Hua Zhao, Eva Albrecht, Tanguy Corre, Erik Ingelsson, Caroline Hayward, Patrik K E Magnusson, Erin N. Smith, Shelia Ulivi, Nicole M. Warrington, Lina Zgaga, Helen Alavere, Najaf Amin, Thor Aspelund, Stefania Bandinelli, Inês Barroso, Gerald S. Berenson, Sven Bergmann, Hannah Blackburn, Eric Boerwinkle, Julie E. Buring, Fabio Busonero, Harry Campbell, Stephen J. Chanock, Wei Chen, Marilyn C. Cornelis, David Couper, Andrea D. Coviello, Pio D'Adamo, Ulf De Faire, Eco J C De Geus, Panos Deloukas, Angela Döring, George Davey Smith, Douglas F. Easton, Gudny Eiriksdottir, Valur Emilsson, Johan Eriksson, Luigi Ferrucci, Aaron R. Folsom, Tatiana Foroud, Melissa Garcia, Paolo Gasparini, Frank Geller, Christian Gieger, Vilmundur Gudnason, Per Hall, Susan E. Hankinson, Liana Ferreli, Andrew C. Heath, Dena G. Hernandez, Albert Hofman, Frank B. Hu, Thomas Illig, Marjo Riitta Järvelin, Andrew D. Johnson, David Karasik, Kay Tee Khaw, Douglas P. Kiel, Tuomas O. Kilpelänen, Ivana Kolcic, Peter Kraft, Lenore J. Launer, Joop S E Laven, Shengxu Li, Jianjun Liu, Daniel Levy, Nicholas G. Martin, Wendy L. McArdle, Mads Melbye, Vincent Mooser, Jeffrey C. Murray, Sarah S. Murray, Michael A. Nalls, Pau Navarro, Mari Nelis, Andrew R. Ness, Kate Northstone, Ben A. Oostra, Munro Peacock, Lyle J. Palmer, Aarno Palotie, Guillaume Paré, Alex N. Parker, Nancy L. Pedersen, Leena Peltonen, Craig E. Pennell, Paul Pharoah, Ozren Polasek, Andrew S. Plump, Anneli Pouta, Eleonora Porcu, Thorunn Rafnar, John P. Rice, Susan M. Ring, Fernando Rivadeneira, Igor Rudan, Cinzia Sala, Veikko Salomaa, Serena Sanna, David Schlessinger, Nicholas J. Schork, Angelo Scuteri, Ayellet V. Segrè, Alan R. Shuldiner, Nicole Soranzo, Ulla Sovio, Sathanur R. Srinivasan, David P. Strachan, Mar Liis Tammesoo, Emmi Tikkanen, Daniela Toniolo, Kim Tsui, Laufey Tryggvadottir, Jonathon Tyrer, Manuela Uda, Rob M. Van Dam, Joyce B J Van Meurs, Peter Vollenweider, Gerard Waeber, Nicholas J. Wareham, Dawn M. Waterworth, Michael N. Weedon, H. Erich Wichmann, Gonneke Willemsen, James F. Wilson, Alan F. Wright, Lauren Young, Guangju Zhai, Wei Vivian Zhuang, Laura J. Bierut, Dorret I. Boomsma, Heather A. Boyd, Laura Crisponi, Ellen W. Demerath, Cornelia M. Van Duijn, Michael J. Econs, Tamara B. Harris, David J. Hunter, Ruth J F Loos, Andres Metspalu, Grant W. Montgomery, Paul M. Ridker, Tim D. Spector, Elizabeth A. Streeten, Kari Stefansson, Unnur Thorsteinsdottir, André G. Uitterlinden, Elisabeth Widen, Joanne M. Murabito, Ken K. Ong, Anna Murray^*

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

425 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1077-1085
Number of pages	9
Journal	Nature Genetics
Volume	42
Issue number	12
DOIs	https://doi.org/10.1038/ng.714
State	Published - Dec 1 2010

Funding

Drug Abuse (NIDA); National Institutes of Health (AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, HHSN268200782096C, M01 RR-00750, MH66206, N01-AG-12100, N01-AG-1-2109, P01-AG-18397, R01-088119, R01-DA013423, RFAHG006033, U01DE018993, U01DE018903, U01HG004422, U01HG004446, U01HL72515, U01 HL84756, U01HG004399, U01HG004402, U01HG004415, U01HG004423, U01HG004436, U01HG004438, U01HG004402, U01HG004446, U01HG004726, U01HG004728, U01HG004729, U01HG004735, U01HG004738, U01HG04424, U10AA008401, U54RR025204-01, UL1RR025005, UL1 RR025774, Z01CP010200, HHSN268200625226C); the National Institute for Health Research Cambridge Biomedical Research Centre; Netherlands Organization for Scientific Research (904-61-193, 575-25-006, 480-04-004, 56-464-14192, NWO 480-05-003, 175.010.2005.011, 911-03-012, 014-93-015); Netherlands Genomic Initiative (NGI, 050-060-810), National Institute on Aging (NIA) Intramural Research Program; and Laboratory of Neurogenetics; US National Institutes of Health Genes, Environment and Health Initiative; Republic of Croatia Ministry of Science, Education and Sports (108-1080315-0302); Robert Dawson Evans Endowment; the Royal Society, Royal Swedish Academy of Science; State of Bavaria, Germany; Susan G. Komen Breast Cancer Foundation; Swedish Foundation for Strategic Research (SSF); Swedish Heart-Lung Foundation; Swedish Ministry of Higher Education and Research; Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation (Ref: 33CSCO-122661, 3100AO-116323/1); the University of Bristol, University of Maryland General Clinical Research Center (M01 RR 16500); the Wellcome Trust (068545/Z/02, 076467/Z/05/Z, 077016/Z/05/Z, 89061/Z/09/Z, strategic award 079895); Western Australian DNA Bank; Western Australian Genetic Epidemiology Resource (see Supplementary Note for extended acknowledgments). Academy of Finland (Finnish Centre of Excellence in Complex Disease Genetics 129680, 120315, 129287, 129494); Affymetrix (N02-HL-6-4278); Agency of Science, Technology and Research of Singapore (A*STAR); Althingi (the Icelandic Parliament); American Heart Association (0855082E); Amgen; Augustinus Foundation; Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498, 619667); Australian Research Council (A7960034, A79801419, A79906588, DP0212016, DP0343921, DP0770096); Baltimore Veterans Administration Medical Center Geriatrics Research; Canadian Institutes of Health Research (grant ID 166067); Cancer Research United Kingdom; the Cariplo Foundation; Center for Disease Control and Prevention (USA), Centre for Medical Systems Biology (CMSB); the Chief Scientist Office of the Scottish Government; Clinical Nutrition Research Unit of Maryland (P30 DK072488); Danish National Research Foundation; Danish Pharmacists’ Fund; the Egmont Foundation; Erasmus Medical Center; Erasmus University; Estonian Government (SF0180142s08); the European Commision (212111 BBMRI, 205419 ECOGENE, 201413 ENGAGE, HEALTH-F2-2008-201865 - GEFOS, HEALTH-F2-2008-35627, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550 HYPERGENES, 245536 OPENGENE, TREAT-OA, GenomEUtwin Project QLG2-CT-2002-01254, EU/QLRT-2001-01254; ERC-230374); European Union framework program 6 EUROSPAN project (LSHG-CT-2006-018947, LSHM-CT-2003-503041); European Regional Development Fund; Faculty of Biology and Medicine of Lausanne, Switzerland; Fondazione Compagnia di San Paolo Health Ministry, Framingham Heart Study (N01-HC-25195); GENEVA Coordinating Center (U01HG004446); German Federal Ministry of Education and Research; German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823); Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Health Fund of the Danish Health Insurance Societies; Helmholtz Zentrum München-German Research Center for Environmental Health; Hjartavernd (the Icelandic Heart Association); Italian Ministry of Health (ICS110.1/RF97.71, RF-FSR-2007-647201); Juvenile Diabetes Research Foundation International (JDRF); Leenaards Foundation; March of Dimes Birth Defects Foundation; the Medical Research Council (G0000934, G0500539, G0701863); National Cancer Institute (CA40356, CA98233, P01CA087969, P01CA055075, CA047988, CA63464, CA54281, CA136792, CA089392, CA104021); Munich Center of Health Sciences (MC Health, LMUinnovativ); National Health and Medical Research Council of Australia (572613 and 003209); National Heart, Lung, and Blood Institute (HL 043851, HL087679, HL69757, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, RC2 HL102419); National Human Genome Research Institute (NHGRI); National Institute of Aging (263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002, AG-16592, Genetics of Reproductive Life Period and Health Outcomes - R21AG032598); National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging ((NIAMS/NIA) R01 AR/AG 41398); National Institute of Child Health and Human Development (HD-061437); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, R01DK058845, U01 DK062418); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Allergy and Infectious Diseases (NIAID); National Institute on

ASJC Scopus subject areas

Genetics

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10.1038/ng.714

Cite this

Elks, C. E., Perry, J. R. B., Sulem, P., Chasman, D. I., Franceschini, N., He, C., Lunetta, K. L., Visser, J. A., Byrne, E. M., Cousminer, D. L., Gudbjartsson, D. F., Esko, T., Feenstra, B., Hottenga, J. J., Koller, D. L., Kutalik, Z., Lin, P., Mangino, M., Marongiu, M., ... Murray, A. (2010). Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nature Genetics, 42(12), 1077-1085. https://doi.org/10.1038/ng.714

@article{de820c8b51464b17b8e0e155f590decc,

title = "Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies",

abstract = "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.",

author = "Elks, {Cathy E.} and Perry, {John R B} and Patrick Sulem and Chasman, {Daniel I.} and Nora Franceschini and Chunyan He and Lunetta, {Kathryn L.} and Visser, {Jenny A.} and Byrne, {Enda M.} and Cousminer, {Diana L.} and Gudbjartsson, {Daniel F.} and T{\~o}nu Esko and Bjarke Feenstra and Hottenga, {Jouke Jan} and Koller, {Daniel L.} and Zolt{\'a}n Kutalik and Peng Lin and Massimo Mangino and Mara Marongiu and McArdle, {Patrick F.} and Smith, {Albert V.} and Lisette Stolk and {Van Wingerden}, {Sophie H.} and Zhao, {Jing Hua} and Eva Albrecht and Tanguy Corre and Erik Ingelsson and Caroline Hayward and Magnusson, {Patrik K E} and Smith, {Erin N.} and Shelia Ulivi and Warrington, {Nicole M.} and Lina Zgaga and Helen Alavere and Najaf Amin and Thor Aspelund and Stefania Bandinelli and In{\^e}s Barroso and Berenson, {Gerald S.} and Sven Bergmann and Hannah Blackburn and Eric Boerwinkle and Buring, {Julie E.} and Fabio Busonero and Harry Campbell and Chanock, {Stephen J.} and Wei Chen and Cornelis, {Marilyn C.} and David Couper and Coviello, {Andrea D.} and Pio D'Adamo and {De Faire}, Ulf and {De Geus}, {Eco J C} and Panos Deloukas and Angela D{\"o}ring and Smith, {George Davey} and Easton, {Douglas F.} and Gudny Eiriksdottir and Valur Emilsson and Johan Eriksson and Luigi Ferrucci and Folsom, {Aaron R.} and Tatiana Foroud and Melissa Garcia and Paolo Gasparini and Frank Geller and Christian Gieger and Vilmundur Gudnason and Per Hall and Hankinson, {Susan E.} and Liana Ferreli and Heath, {Andrew C.} and Hernandez, {Dena G.} and Albert Hofman and Hu, {Frank B.} and Thomas Illig and J{\"a}rvelin, {Marjo Riitta} and Johnson, {Andrew D.} and David Karasik and Khaw, {Kay Tee} and Kiel, {Douglas P.} and Kilpel{\"a}nen, {Tuomas O.} and Ivana Kolcic and Peter Kraft and Launer, {Lenore J.} and Laven, {Joop S E} and Shengxu Li and Jianjun Liu and Daniel Levy and Martin, {Nicholas G.} and McArdle, {Wendy L.} and Mads Melbye and Vincent Mooser and Murray, {Jeffrey C.} and Murray, {Sarah S.} and Nalls, {Michael A.} and Pau Navarro and Mari Nelis and Ness, {Andrew R.} and Kate Northstone and Oostra, {Ben A.} and Munro Peacock and Palmer, {Lyle J.} and Aarno Palotie and Guillaume Par{\'e} and Parker, {Alex N.} and Pedersen, {Nancy L.} and Leena Peltonen and Pennell, {Craig E.} and Paul Pharoah and Ozren Polasek and Plump, {Andrew S.} and Anneli Pouta and Eleonora Porcu and Thorunn Rafnar and Rice, {John P.} and Ring, {Susan M.} and Fernando Rivadeneira and Igor Rudan and Cinzia Sala and Veikko Salomaa and Serena Sanna and David Schlessinger and Schork, {Nicholas J.} and Angelo Scuteri and Segr{\`e}, {Ayellet V.} and Shuldiner, {Alan R.} and Nicole Soranzo and Ulla Sovio and Srinivasan, {Sathanur R.} and Strachan, {David P.} and Tammesoo, {Mar Liis} and Emmi Tikkanen and Daniela Toniolo and Kim Tsui and Laufey Tryggvadottir and Jonathon Tyrer and Manuela Uda and {Van Dam}, {Rob M.} and {Van Meurs}, {Joyce B J} and Peter Vollenweider and Gerard Waeber and Wareham, {Nicholas J.} and Waterworth, {Dawn M.} and Weedon, {Michael N.} and Wichmann, {H. Erich} and Gonneke Willemsen and Wilson, {James F.} and Wright, {Alan F.} and Lauren Young and Guangju Zhai and Zhuang, {Wei Vivian} and Bierut, {Laura J.} and Boomsma, {Dorret I.} and Boyd, {Heather A.} and Laura Crisponi and Demerath, {Ellen W.} and {Van Duijn}, {Cornelia M.} and Econs, {Michael J.} and Harris, {Tamara B.} and Hunter, {David J.} and Loos, {Ruth J F} and Andres Metspalu and Montgomery, {Grant W.} and Ridker, {Paul M.} and Spector, {Tim D.} and Streeten, {Elizabeth A.} and Kari Stefansson and Unnur Thorsteinsdottir and Uitterlinden, {Andr{\'e} G.} and Elisabeth Widen and Murabito, {Joanne M.} and Ong, {Ken K.} and Anna Murray",

note = "Funding Information: Drug Abuse (NIDA); National Institutes of Health (AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, HHSN268200782096C, M01 RR-00750, MH66206, N01-AG-12100, N01-AG-1-2109, P01-AG-18397, R01-088119, R01-DA013423, RFAHG006033, U01DE018993, U01DE018903, U01HG004422, U01HG004446, U01HL72515, U01 HL84756, U01HG004399, U01HG004402, U01HG004415, U01HG004423, U01HG004436, U01HG004438, U01HG004402, U01HG004446, U01HG004726, U01HG004728, U01HG004729, U01HG004735, U01HG004738, U01HG04424, U10AA008401, U54RR025204-01, UL1RR025005, UL1 RR025774, Z01CP010200, HHSN268200625226C); the National Institute for Health Research Cambridge Biomedical Research Centre; Netherlands Organization for Scientific Research (904-61-193, 575-25-006, 480-04-004, 56-464-14192, NWO 480-05-003, 175.010.2005.011, 911-03-012, 014-93-015); Netherlands Genomic Initiative (NGI, 050-060-810), National Institute on Aging (NIA) Intramural Research Program; and Laboratory of Neurogenetics; US National Institutes of Health Genes, Environment and Health Initiative; Republic of Croatia Ministry of Science, Education and Sports (108-1080315-0302); Robert Dawson Evans Endowment; the Royal Society, Royal Swedish Academy of Science; State of Bavaria, Germany; Susan G. Komen Breast Cancer Foundation; Swedish Foundation for Strategic Research (SSF); Swedish Heart-Lung Foundation; Swedish Ministry of Higher Education and Research; Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation (Ref: 33CSCO-122661, 3100AO-116323/1); the University of Bristol, University of Maryland General Clinical Research Center (M01 RR 16500); the Wellcome Trust (068545/Z/02, 076467/Z/05/Z, 077016/Z/05/Z, 89061/Z/09/Z, strategic award 079895); Western Australian DNA Bank; Western Australian Genetic Epidemiology Resource (see Supplementary Note for extended acknowledgments). Funding Information: Academy of Finland (Finnish Centre of Excellence in Complex Disease Genetics 129680, 120315, 129287, 129494); Affymetrix (N02-HL-6-4278); Agency of Science, Technology and Research of Singapore (A*STAR); Althingi (the Icelandic Parliament); American Heart Association (0855082E); Amgen; Augustinus Foundation; Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498, 619667); Australian Research Council (A7960034, A79801419, A79906588, DP0212016, DP0343921, DP0770096); Baltimore Veterans Administration Medical Center Geriatrics Research; Canadian Institutes of Health Research (grant ID 166067); Cancer Research United Kingdom; the Cariplo Foundation; Center for Disease Control and Prevention (USA), Centre for Medical Systems Biology (CMSB); the Chief Scientist Office of the Scottish Government; Clinical Nutrition Research Unit of Maryland (P30 DK072488); Danish National Research Foundation; Danish Pharmacists{\textquoteright} Fund; the Egmont Foundation; Erasmus Medical Center; Erasmus University; Estonian Government (SF0180142s08); the European Commision (212111 BBMRI, 205419 ECOGENE, 201413 ENGAGE, HEALTH-F2-2008-201865 - GEFOS, HEALTH-F2-2008-35627, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550 HYPERGENES, 245536 OPENGENE, TREAT-OA, GenomEUtwin Project QLG2-CT-2002-01254, EU/QLRT-2001-01254; ERC-230374); European Union framework program 6 EUROSPAN project (LSHG-CT-2006-018947, LSHM-CT-2003-503041); European Regional Development Fund; Faculty of Biology and Medicine of Lausanne, Switzerland; Fondazione Compagnia di San Paolo Health Ministry, Framingham Heart Study (N01-HC-25195); GENEVA Coordinating Center (U01HG004446); German Federal Ministry of Education and Research; German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823); Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Health Fund of the Danish Health Insurance Societies; Helmholtz Zentrum M{\"u}nchen-German Research Center for Environmental Health; Hjartavernd (the Icelandic Heart Association); Italian Ministry of Health (ICS110.1/RF97.71, RF-FSR-2007-647201); Juvenile Diabetes Research Foundation International (JDRF); Leenaards Foundation; March of Dimes Birth Defects Foundation; the Medical Research Council (G0000934, G0500539, G0701863); National Cancer Institute (CA40356, CA98233, P01CA087969, P01CA055075, CA047988, CA63464, CA54281, CA136792, CA089392, CA104021); Munich Center of Health Sciences (MC Health, LMUinnovativ); National Health and Medical Research Council of Australia (572613 and 003209); National Heart, Lung, and Blood Institute (HL 043851, HL087679, HL69757, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, RC2 HL102419); National Human Genome Research Institute (NHGRI); National Institute of Aging (263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002, AG-16592, Genetics of Reproductive Life Period and Health Outcomes - R21AG032598); National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging ((NIAMS/NIA) R01 AR/AG 41398); National Institute of Child Health and Human Development (HD-061437); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, R01DK058845, U01 DK062418); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Allergy and Infectious Diseases (NIAID); National Institute on",

year = "2010",

month = dec,

day = "1",

doi = "10.1038/ng.714",

language = "English (US)",

volume = "42",

pages = "1077--1085",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "12",

}

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, JJ, 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, Gudnason, V, Hall, P, Hankinson, SE, Ferreli, L, Heath, AC, Hernandez, DG, Hofman, A, Hu, FB, Illig, T, Järvelin, MR, Johnson, AD, Karasik, D, Khaw, KT, Kiel, DP, Kilpelänen, 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, ML, 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 2010, 'Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies', Nature Genetics, vol. 42, no. 12, pp. 1077-1085. https://doi.org/10.1038/ng.714

TY - JOUR

T1 - Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

AU - Elks, Cathy E.

AU - Perry, John R B

AU - Sulem, Patrick

AU - Chasman, Daniel I.

AU - Franceschini, Nora

AU - He, Chunyan

AU - Lunetta, Kathryn L.

AU - Visser, Jenny A.

AU - Byrne, Enda M.

AU - Cousminer, Diana L.

AU - Gudbjartsson, Daniel F.

AU - Esko, Tõnu

AU - Feenstra, Bjarke

AU - Hottenga, Jouke Jan

AU - Koller, Daniel L.

AU - Kutalik, Zoltán

AU - Lin, Peng

AU - Mangino, Massimo

AU - Marongiu, Mara

AU - McArdle, Patrick F.

AU - Smith, Albert V.

AU - Stolk, Lisette

AU - Van Wingerden, Sophie H.

AU - Zhao, Jing Hua

AU - Albrecht, Eva

AU - Corre, Tanguy

AU - Ingelsson, Erik

AU - Hayward, Caroline

AU - Magnusson, Patrik K E

AU - Smith, Erin N.

AU - Ulivi, Shelia

AU - Warrington, Nicole M.

AU - Zgaga, Lina

AU - Alavere, Helen

AU - Amin, Najaf

AU - Aspelund, Thor

AU - Bandinelli, Stefania

AU - Barroso, Inês

AU - Berenson, Gerald S.

AU - Bergmann, Sven

AU - Blackburn, Hannah

AU - Boerwinkle, Eric

AU - Buring, Julie E.

AU - Busonero, Fabio

AU - Campbell, Harry

AU - Chanock, Stephen J.

AU - Chen, Wei

AU - Cornelis, Marilyn C.

AU - Couper, David

AU - Coviello, Andrea D.

AU - D'Adamo, Pio

AU - De Faire, Ulf

AU - De Geus, Eco J C

AU - Deloukas, Panos

AU - Döring, Angela

AU - Smith, George Davey

AU - Easton, Douglas F.

AU - Eiriksdottir, Gudny

AU - Emilsson, Valur

AU - Eriksson, Johan

AU - Ferrucci, Luigi

AU - Folsom, Aaron R.

AU - Foroud, Tatiana

AU - Garcia, Melissa

AU - Gasparini, Paolo

AU - Geller, Frank

AU - Gieger, Christian

AU - Gudnason, Vilmundur

AU - Hall, Per

AU - Hankinson, Susan E.

AU - Ferreli, Liana

AU - Heath, Andrew C.

AU - Hernandez, Dena G.

AU - Hofman, Albert

AU - Hu, Frank B.

AU - Illig, Thomas

AU - Järvelin, Marjo Riitta

AU - Johnson, Andrew D.

AU - Karasik, David

AU - Khaw, Kay Tee

AU - Kiel, Douglas P.

AU - Kilpelänen, Tuomas O.

AU - Kolcic, Ivana

AU - Kraft, Peter

AU - Launer, Lenore J.

AU - Laven, Joop S E

AU - Li, Shengxu

AU - Liu, Jianjun

AU - Levy, Daniel

AU - Martin, Nicholas G.

AU - McArdle, Wendy L.

AU - Melbye, Mads

AU - Mooser, Vincent

AU - Murray, Jeffrey C.

AU - Murray, Sarah S.

AU - Nalls, Michael A.

AU - Navarro, Pau

AU - Nelis, Mari

AU - Ness, Andrew R.

AU - Northstone, Kate

AU - Oostra, Ben A.

AU - Peacock, Munro

AU - Palmer, Lyle J.

AU - Palotie, Aarno

AU - Paré, Guillaume

AU - Parker, Alex N.

AU - Pedersen, Nancy L.

AU - Peltonen, Leena

AU - Pennell, Craig E.

AU - Pharoah, Paul

AU - Polasek, Ozren

AU - Plump, Andrew S.

AU - Pouta, Anneli

AU - Porcu, Eleonora

AU - Rafnar, Thorunn

AU - Rice, John P.

AU - Ring, Susan M.

AU - Rivadeneira, Fernando

AU - Rudan, Igor

AU - Sala, Cinzia

AU - Salomaa, Veikko

AU - Sanna, Serena

AU - Schlessinger, David

AU - Schork, Nicholas J.

AU - Scuteri, Angelo

AU - Segrè, Ayellet V.

AU - Shuldiner, Alan R.

AU - Soranzo, Nicole

AU - Sovio, Ulla

AU - Srinivasan, Sathanur R.

AU - Strachan, David P.

AU - Tammesoo, Mar Liis

AU - Tikkanen, Emmi

AU - Toniolo, Daniela

AU - Tsui, Kim

AU - Tryggvadottir, Laufey

AU - Tyrer, Jonathon

AU - Uda, Manuela

AU - Van Dam, Rob M.

AU - Van Meurs, Joyce B J

AU - Vollenweider, Peter

AU - Waeber, Gerard

AU - Wareham, Nicholas J.

AU - Waterworth, Dawn M.

AU - Weedon, Michael N.

AU - Wichmann, H. Erich

AU - Willemsen, Gonneke

AU - Wilson, James F.

AU - Wright, Alan F.

AU - Young, Lauren

AU - Zhai, Guangju

AU - Zhuang, Wei Vivian

AU - Bierut, Laura J.

AU - Boomsma, Dorret I.

AU - Boyd, Heather A.

AU - Crisponi, Laura

AU - Demerath, Ellen W.

AU - Van Duijn, Cornelia M.

AU - Econs, Michael J.

AU - Harris, Tamara B.

AU - Hunter, David J.

AU - Loos, Ruth J F

AU - Metspalu, Andres

AU - Montgomery, Grant W.

AU - Ridker, Paul M.

AU - Spector, Tim D.

AU - Streeten, Elizabeth A.

AU - Stefansson, Kari

AU - Thorsteinsdottir, Unnur

AU - Uitterlinden, André G.

AU - Widen, Elisabeth

AU - Murabito, Joanne M.

AU - Ong, Ken K.

AU - Murray, Anna

N1 - Funding Information: Drug Abuse (NIDA); National Institutes of Health (AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, HHSN268200782096C, M01 RR-00750, MH66206, N01-AG-12100, N01-AG-1-2109, P01-AG-18397, R01-088119, R01-DA013423, RFAHG006033, U01DE018993, U01DE018903, U01HG004422, U01HG004446, U01HL72515, U01 HL84756, U01HG004399, U01HG004402, U01HG004415, U01HG004423, U01HG004436, U01HG004438, U01HG004402, U01HG004446, U01HG004726, U01HG004728, U01HG004729, U01HG004735, U01HG004738, U01HG04424, U10AA008401, U54RR025204-01, UL1RR025005, UL1 RR025774, Z01CP010200, HHSN268200625226C); the National Institute for Health Research Cambridge Biomedical Research Centre; Netherlands Organization for Scientific Research (904-61-193, 575-25-006, 480-04-004, 56-464-14192, NWO 480-05-003, 175.010.2005.011, 911-03-012, 014-93-015); Netherlands Genomic Initiative (NGI, 050-060-810), National Institute on Aging (NIA) Intramural Research Program; and Laboratory of Neurogenetics; US National Institutes of Health Genes, Environment and Health Initiative; Republic of Croatia Ministry of Science, Education and Sports (108-1080315-0302); Robert Dawson Evans Endowment; the Royal Society, Royal Swedish Academy of Science; State of Bavaria, Germany; Susan G. Komen Breast Cancer Foundation; Swedish Foundation for Strategic Research (SSF); Swedish Heart-Lung Foundation; Swedish Ministry of Higher Education and Research; Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation (Ref: 33CSCO-122661, 3100AO-116323/1); the University of Bristol, University of Maryland General Clinical Research Center (M01 RR 16500); the Wellcome Trust (068545/Z/02, 076467/Z/05/Z, 077016/Z/05/Z, 89061/Z/09/Z, strategic award 079895); Western Australian DNA Bank; Western Australian Genetic Epidemiology Resource (see Supplementary Note for extended acknowledgments). Funding Information: Academy of Finland (Finnish Centre of Excellence in Complex Disease Genetics 129680, 120315, 129287, 129494); Affymetrix (N02-HL-6-4278); Agency of Science, Technology and Research of Singapore (A*STAR); Althingi (the Icelandic Parliament); American Heart Association (0855082E); Amgen; Augustinus Foundation; Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498, 619667); Australian Research Council (A7960034, A79801419, A79906588, DP0212016, DP0343921, DP0770096); Baltimore Veterans Administration Medical Center Geriatrics Research; Canadian Institutes of Health Research (grant ID 166067); Cancer Research United Kingdom; the Cariplo Foundation; Center for Disease Control and Prevention (USA), Centre for Medical Systems Biology (CMSB); the Chief Scientist Office of the Scottish Government; Clinical Nutrition Research Unit of Maryland (P30 DK072488); Danish National Research Foundation; Danish Pharmacists’ Fund; the Egmont Foundation; Erasmus Medical Center; Erasmus University; Estonian Government (SF0180142s08); the European Commision (212111 BBMRI, 205419 ECOGENE, 201413 ENGAGE, HEALTH-F2-2008-201865 - GEFOS, HEALTH-F2-2008-35627, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550 HYPERGENES, 245536 OPENGENE, TREAT-OA, GenomEUtwin Project QLG2-CT-2002-01254, EU/QLRT-2001-01254; ERC-230374); European Union framework program 6 EUROSPAN project (LSHG-CT-2006-018947, LSHM-CT-2003-503041); European Regional Development Fund; Faculty of Biology and Medicine of Lausanne, Switzerland; Fondazione Compagnia di San Paolo Health Ministry, Framingham Heart Study (N01-HC-25195); GENEVA Coordinating Center (U01HG004446); German Federal Ministry of Education and Research; German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823); Giorgi-Cavaglieri Foundation; GlaxoSmithKline; Health Fund of the Danish Health Insurance Societies; Helmholtz Zentrum München-German Research Center for Environmental Health; Hjartavernd (the Icelandic Heart Association); Italian Ministry of Health (ICS110.1/RF97.71, RF-FSR-2007-647201); Juvenile Diabetes Research Foundation International (JDRF); Leenaards Foundation; March of Dimes Birth Defects Foundation; the Medical Research Council (G0000934, G0500539, G0701863); National Cancer Institute (CA40356, CA98233, P01CA087969, P01CA055075, CA047988, CA63464, CA54281, CA136792, CA089392, CA104021); Munich Center of Health Sciences (MC Health, LMUinnovativ); National Health and Medical Research Council of Australia (572613 and 003209); National Heart, Lung, and Blood Institute (HL 043851, HL087679, HL69757, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694, RC2 HL102419); National Human Genome Research Institute (NHGRI); National Institute of Aging (263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002, AG-16592, Genetics of Reproductive Life Period and Health Outcomes - R21AG032598); National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute on Aging ((NIAMS/NIA) R01 AR/AG 41398); National Institute of Child Health and Human Development (HD-061437); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, R01DK058845, U01 DK062418); National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Allergy and Infectious Diseases (NIAID); National Institute on

PY - 2010/12/1

Y1 - 2010/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84947899470&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947899470&partnerID=8YFLogxK

U2 - 10.1038/ng.714

DO - 10.1038/ng.714

M3 - Article

C2 - 21102462

AN - SCOPUS:84947899470

SN - 1061-4036

VL - 42

SP - 1077

EP - 1085

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

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