Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

Lisette Stolk; John R.B. Perry; Daniel I. Chasman; Chunyan He; Massimo Mangino; Patrick Sulem; Maja Barbalic; Linda Broer; Enda M. Byrne; Florian Ernst; Tmu Esko; Nora Franceschini; Daniel F. Gudbjartsson; Jouke Jan Hottenga; Peter Kraft; Patrick F. McArdle; Eleonora Porcu; So Youn Shin; Albert V. Smith; Sophie Van Wingerden; Guangju Zhai; Wei V. Zhuang; Eva Albrecht; Behrooz Z. Alizadeh; Thor Aspelund; Stefania Bandinelli; Lovorka Barac Lauc; Jacques S. Beckmann; Mladen Boban; Eric Boerwinkle; Frank J. Broekmans; Andrea Burri; Harry Campbell; Stephen J. Chanock; Constance Chen; Marilyn C. Cornelis; Tanguy Corre; Andrea D. Coviello; Pio D'Adamo; Gail Davies; Ulf De Faire; Eco J.C. De Geus; Ian J. Deary; George V.Z. Dedoussis; Panagiotis Deloukas; Shah Ebrahim; Gudny Eiriksdottir; Valur Emilsson; Johan G. Eriksson; Bart C.J.M. Fauser; Liana Ferreli; Luigi Ferrucci; Krista Fischer; Aaron R. Folsom; Melissa E. Garcia; Paolo Gasparini; Christian Gieger; Nicole Glazer; Diederick E. Grobbee; Per Hall; Toomas Haller; Susan E. Hankinson; Merli Hass; Caroline Hayward; Andrew C. Heath; Albert Hofman; Erik Ingelsson; A. Cecile J.W. Janssens; Andrew D. Johnson; David Karasik; Sharon L.R. Kardia; Jules Keyzer; Douglas P. Kiel; Ivana Kolcic; Zoltn Kutalik; Jari Lahti; Sandra Lai; Triin Laisk; Joop S.E. Laven; Debbie A. Lawlor; Jianjun Liu; Lorna M. Lopez; Yvonne V. Louwers; Patrik K.E. Magnusson; Mara Marongiu; Nicholas G. Martin; Irena Martinovic Klaric; Corrado Masciullo; Barbara McKnight; Sarah E. Medland; David Melzer; Vincent Mooser; Pau Navarro; Anne B. Newman; Dale R. Nyholt; N. Charlotte Onland-Moret; Aarno Palotie; Guillaume Paré; Alex N. Parker; Nancy L. Pedersen; Petra H.M. Peeters; Giorgio Pistis; Andrew S. Plump; Ozren Polasek; Victor J.M. Pop; Bruce M. Psaty; Katri R Currency Signikkönen; Emil Rehnberg; Jerome I. Rotter; Igor Rudan; Cinzia Sala; Andres Salumets; Angelo Scuteri; Andrew Singleton; Jennifer A. Smith; Harold Snieder; Nicole Soranzo; Simon N. Stacey; John M. Starr; Maria G. Stathopoulou; Kathleen Stirrups; Ronald P. Stolk; Unnur Styrkarsdottir; Yan V. Sun; Albert Tenesa; Barbara Thorand; Daniela Toniolo; Laufey Tryggvadottir; Kim Tsui; Sheila Ulivi; Rob M. Van Dam; Yvonne T. Van Der Schouw; Carla H. Van Gils; Peter Van Nierop; Jacqueline M. Vink; Peter M. Visscher; Marlies Voorhuis; Gérard Waeber; Henri Wallaschofski; H. Erich Wichmann; Elisabeth Widen; Colette J.M. Wijnands-Van Gent; Gonneke Willemsen; James F. Wilson; Bruce H.R. Wolffenbuttel; Alan F. Wright; Laura M. Yerges-Armstrong; Tatijana Zemunik; Lina Zgaga; M. Carola Zillikens; Marek Zygmunt; Alice M. Arnold; Dorret I. Boomsma; Julie E. Buring; Laura Crisponi; Ellen W. Demerath; Vilmundur Gudnason; Tamara B. Harris; Frank B. Hu; David J. Hunter; Lenore J. Launer; Andres Metspalu; Grant W. Montgomery; Ben A. Oostra; Paul M. Ridker; Serena Sanna; David Schlessinger; Tim D. Spector; Kari Stefansson; Elizabeth A. Streeten; Unnur Thorsteinsdottir; Manuela Uda; André G. Uitterlinden; Cornelia M. Van Duijn; Henry Völzke; Anna Murray; Joanne M. Murabito; Jenny A. Visser; Kathryn L. Lunetta

doi:10.1038/ng.1051

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

Lisette Stolk, John R.B. Perry, Daniel I. Chasman, Chunyan He, Massimo Mangino, Patrick Sulem, Maja Barbalic, Linda Broer, Enda M. Byrne, Florian Ernst, Tmu Esko, Nora Franceschini, Daniel F. Gudbjartsson, Jouke Jan Hottenga, Peter Kraft, Patrick F. McArdle, Eleonora Porcu, So Youn Shin, Albert V. Smith, Sophie Van WingerdenGuangju Zhai, Wei V. Zhuang, Eva Albrecht, Behrooz Z. Alizadeh, Thor Aspelund, Stefania Bandinelli, Lovorka Barac Lauc, Jacques S. Beckmann, Mladen Boban, Eric Boerwinkle, Frank J. Broekmans, Andrea Burri, Harry Campbell, Stephen J. Chanock, Constance Chen, Marilyn C. Cornelis, Tanguy Corre, Andrea D. Coviello, Pio D'Adamo, Gail Davies, Ulf De Faire, Eco J.C. De Geus, Ian J. Deary, George V.Z. Dedoussis, Panagiotis Deloukas, Shah Ebrahim, Gudny Eiriksdottir, Valur Emilsson, Johan G. Eriksson, Bart C.J.M. Fauser, Liana Ferreli, Luigi Ferrucci, Krista Fischer, Aaron R. Folsom, Melissa E. Garcia, Paolo Gasparini, Christian Gieger, Nicole Glazer, Diederick E. Grobbee, Per Hall, Toomas Haller, Susan E. Hankinson, Merli Hass, Caroline Hayward, Andrew C. Heath, Albert Hofman, Erik Ingelsson, A. Cecile J.W. Janssens, Andrew D. Johnson, David Karasik, Sharon L.R. Kardia, Jules Keyzer, Douglas P. Kiel, Ivana Kolcic, Zoltn Kutalik, Jari Lahti, Sandra Lai, Triin Laisk, Joop S.E. Laven, Debbie A. Lawlor, Jianjun Liu, Lorna M. Lopez, Yvonne V. Louwers, Patrik K.E. Magnusson, Mara Marongiu, Nicholas G. Martin, Irena Martinovic Klaric, Corrado Masciullo, Barbara McKnight, Sarah E. Medland, David Melzer, Vincent Mooser, Pau Navarro, Anne B. Newman, Dale R. Nyholt, N. Charlotte Onland-Moret, Aarno Palotie, Guillaume Paré, Alex N. Parker, Nancy L. Pedersen, Petra H.M. Peeters, Giorgio Pistis, Andrew S. Plump, Ozren Polasek, Victor J.M. Pop, Bruce M. Psaty, Katri R Currency Signikkönen, Emil Rehnberg, Jerome I. Rotter, Igor Rudan, Cinzia Sala, Andres Salumets, Angelo Scuteri, Andrew Singleton, Jennifer A. Smith, Harold Snieder, Nicole Soranzo, Simon N. Stacey, John M. Starr, Maria G. Stathopoulou, Kathleen Stirrups, Ronald P. Stolk, Unnur Styrkarsdottir, Yan V. Sun, Albert Tenesa, Barbara Thorand, Daniela Toniolo, Laufey Tryggvadottir, Kim Tsui, Sheila Ulivi, Rob M. Van Dam, Yvonne T. Van Der Schouw, Carla H. Van Gils, Peter Van Nierop, Jacqueline M. Vink, Peter M. Visscher, Marlies Voorhuis, Gérard Waeber, Henri Wallaschofski, H. Erich Wichmann, Elisabeth Widen, Colette J.M. Wijnands-Van Gent, Gonneke Willemsen, James F. Wilson, Bruce H.R. Wolffenbuttel, Alan F. Wright, Laura M. Yerges-Armstrong, Tatijana Zemunik, Lina Zgaga, M. Carola Zillikens, Marek Zygmunt, Alice M. Arnold, Dorret I. Boomsma, Julie E. Buring, Laura Crisponi, Ellen W. Demerath, Vilmundur Gudnason, Tamara B. Harris, Frank B. Hu, David J. Hunter, Lenore J. Launer, Andres Metspalu, Grant W. Montgomery, Ben A. Oostra, Paul M. Ridker, Serena Sanna, David Schlessinger, Tim D. Spector, Kari Stefansson, Elizabeth A. Streeten, Unnur Thorsteinsdottir, Manuela Uda, André G. Uitterlinden, Cornelia M. Van Duijn, Henry Völzke, Anna Murray, Joanne M. Murabito, Jenny A. Visser, Kathryn L. Lunetta

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

218 Scopus citations

Abstract

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 - 10 g8). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-I °B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

Original language	English (US)
Pages (from-to)	260-268
Number of pages	9
Journal	Nature genetics
Volume	44
Issue number	3
DOIs	https://doi.org/10.1038/ng.1051
State	Published - Mar 2012
Externally published	Yes

ASJC Scopus subject areas

Genetics

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10.1038/ng.1051

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Stolk, L., Perry, J. R. B., Chasman, D. I., He, C., Mangino, M., Sulem, P., Barbalic, M., Broer, L., Byrne, E. M., Ernst, F., Esko, T., Franceschini, N., Gudbjartsson, D. F., Hottenga, J. J., Kraft, P., McArdle, P. F., Porcu, E., Shin, S. Y., Smith, A. V., ... Lunetta, K. L. (2012). Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nature genetics, 44(3), 260-268. https://doi.org/10.1038/ng.1051

Stolk, L, Perry, JRB, Chasman, DI, He, C, Mangino, M, Sulem, P, Barbalic, M, Broer, L, Byrne, EM, Ernst, F, Esko, T, Franceschini, N, Gudbjartsson, DF, Hottenga, JJ, Kraft, P, McArdle, PF, Porcu, E, Shin, SY, Smith, AV, Van Wingerden, S, Zhai, G, Zhuang, WV, Albrecht, E, Alizadeh, BZ, Aspelund, T, Bandinelli, S, Lauc, LB, Beckmann, JS, Boban, M, Boerwinkle, E, Broekmans, FJ, Burri, A, Campbell, H, Chanock, SJ, Chen, C, Cornelis, MC, Corre, T, Coviello, AD, D'Adamo, P, Davies, G, De Faire, U, De Geus, EJC, Deary, IJ, Dedoussis, GVZ, Deloukas, P, Ebrahim, S, Eiriksdottir, G, Emilsson, V, Eriksson, JG, Fauser, BCJM, Ferreli, L, Ferrucci, L, Fischer, K, Folsom, AR, Garcia, ME, Gasparini, P, Gieger, C, Glazer, N, Grobbee, DE, Hall, P, Haller, T, Hankinson, SE, Hass, M, Hayward, C, Heath, AC, Hofman, A, Ingelsson, E, Janssens, ACJW, Johnson, AD, Karasik, D, Kardia, SLR, Keyzer, J, Kiel, DP, Kolcic, I, Kutalik, Z, Lahti, J, Lai, S, Laisk, T, Laven, JSE, Lawlor, DA, Liu, J, Lopez, LM, Louwers, YV, Magnusson, PKE, Marongiu, M, Martin, NG, Klaric, IM, Masciullo, C, McKnight, B, Medland, SE, Melzer, D, Mooser, V, Navarro, P, Newman, AB, Nyholt, DR, Onland-Moret, NC, Palotie, A, Paré, G, Parker, AN, Pedersen, NL, Peeters, PHM, Pistis, G, Plump, AS, Polasek, O, Pop, VJM, Psaty, BM, R Currency Signikkönen, K, Rehnberg, E, Rotter, JI, Rudan, I, Sala, C, Salumets, A, Scuteri, A, Singleton, A, Smith, JA, Snieder, H, Soranzo, N, Stacey, SN, Starr, JM, Stathopoulou, MG, Stirrups, K, Stolk, RP, Styrkarsdottir, U, Sun, YV, Tenesa, A, Thorand, B, Toniolo, D, Tryggvadottir, L, Tsui, K, Ulivi, S, Van Dam, RM, Van Der Schouw, YT, Van Gils, CH, Van Nierop, P, Vink, JM, Visscher, PM, Voorhuis, M, Waeber, G, Wallaschofski, H, Wichmann, HE, Widen, E, Wijnands-Van Gent, CJM, Willemsen, G, Wilson, JF, Wolffenbuttel, BHR, Wright, AF, Yerges-Armstrong, LM, Zemunik, T, Zgaga, L, Zillikens, MC, Zygmunt, M, Arnold, AM, Boomsma, DI, Buring, JE, Crisponi, L, Demerath, EW, Gudnason, V, Harris, TB, Hu, FB, Hunter, DJ, Launer, LJ, Metspalu, A, Montgomery, GW, Oostra, BA, Ridker, PM, Sanna, S, Schlessinger, D, Spector, TD, Stefansson, K, Streeten, EA, Thorsteinsdottir, U, Uda, M, Uitterlinden, AG, Van Duijn, CM, Völzke, H, Murray, A, Murabito, JM, Visser, JA & Lunetta, KL 2012, 'Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways', Nature genetics, vol. 44, no. 3, pp. 260-268. https://doi.org/10.1038/ng.1051

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title = "Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways",

abstract = "To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 - 10 g8). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-I °B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.",

author = "Lisette Stolk and Perry, {John R.B.} and Chasman, {Daniel I.} and Chunyan He and Massimo Mangino and Patrick Sulem and Maja Barbalic and Linda Broer and Byrne, {Enda M.} and Florian Ernst and Tmu Esko and Nora Franceschini and Gudbjartsson, {Daniel F.} and Hottenga, {Jouke Jan} and Peter Kraft and McArdle, {Patrick F.} and Eleonora Porcu and Shin, {So Youn} and Smith, {Albert V.} and {Van Wingerden}, Sophie and Guangju Zhai and Zhuang, {Wei V.} and Eva Albrecht and Alizadeh, {Behrooz Z.} and Thor Aspelund and Stefania Bandinelli and Lauc, {Lovorka Barac} and Beckmann, {Jacques S.} and Mladen Boban and Eric Boerwinkle and Broekmans, {Frank J.} and Andrea Burri and Harry Campbell and Chanock, {Stephen J.} and Constance Chen and Cornelis, {Marilyn C.} and Tanguy Corre and Coviello, {Andrea D.} and Pio D'Adamo and Gail Davies and {De Faire}, Ulf and {De Geus}, {Eco J.C.} and Deary, {Ian J.} and Dedoussis, {George V.Z.} and Panagiotis Deloukas and Shah Ebrahim and Gudny Eiriksdottir and Valur Emilsson and Eriksson, {Johan G.} and Fauser, {Bart C.J.M.} and Liana Ferreli and Luigi Ferrucci and Krista Fischer and Folsom, {Aaron R.} and Garcia, {Melissa E.} and Paolo Gasparini and Christian Gieger and Nicole Glazer and Grobbee, {Diederick E.} and Per Hall and Toomas Haller and Hankinson, {Susan E.} and Merli Hass and Caroline Hayward and Heath, {Andrew C.} and Albert Hofman and Erik Ingelsson and Janssens, {A. Cecile J.W.} and Johnson, {Andrew D.} and David Karasik and Kardia, {Sharon L.R.} and Jules Keyzer and Kiel, {Douglas P.} and Ivana Kolcic and Zoltn Kutalik and Jari Lahti and Sandra Lai and Triin Laisk and Laven, {Joop S.E.} and Lawlor, {Debbie A.} and Jianjun Liu and Lopez, {Lorna M.} and Louwers, {Yvonne V.} and Magnusson, {Patrik K.E.} and Mara Marongiu and Martin, {Nicholas G.} and Klaric, {Irena Martinovic} and Corrado Masciullo and Barbara McKnight and Medland, {Sarah E.} and David Melzer and Vincent Mooser and Pau Navarro and Newman, {Anne B.} and Nyholt, {Dale R.} and Onland-Moret, {N. Charlotte} and Aarno Palotie and Guillaume Par{\'e} and Parker, {Alex N.} and Pedersen, {Nancy L.} and Peeters, {Petra H.M.} and Giorgio Pistis and Plump, {Andrew S.} and Ozren Polasek and Pop, {Victor J.M.} and Psaty, {Bruce M.} and {R Currency Signikk{\"o}nen}, Katri and Emil Rehnberg and Rotter, {Jerome I.} and Igor Rudan and Cinzia Sala and Andres Salumets and Angelo Scuteri and Andrew Singleton and Smith, {Jennifer A.} and Harold Snieder and Nicole Soranzo and Stacey, {Simon N.} and Starr, {John M.} and Stathopoulou, {Maria G.} and Kathleen Stirrups and Stolk, {Ronald P.} and Unnur Styrkarsdottir and Sun, {Yan V.} and Albert Tenesa and Barbara Thorand and Daniela Toniolo and Laufey Tryggvadottir and Kim Tsui and Sheila Ulivi and {Van Dam}, {Rob M.} and {Van Der Schouw}, {Yvonne T.} and {Van Gils}, {Carla H.} and {Van Nierop}, Peter and Vink, {Jacqueline M.} and Visscher, {Peter M.} and Marlies Voorhuis and G{\'e}rard Waeber and Henri Wallaschofski and Wichmann, {H. Erich} and Elisabeth Widen and {Wijnands-Van Gent}, {Colette J.M.} and Gonneke Willemsen and Wilson, {James F.} and Wolffenbuttel, {Bruce H.R.} and Wright, {Alan F.} and Yerges-Armstrong, {Laura M.} and Tatijana Zemunik and Lina Zgaga and Zillikens, {M. Carola} and Marek Zygmunt and Arnold, {Alice M.} and Boomsma, {Dorret I.} and Buring, {Julie E.} and Laura Crisponi and Demerath, {Ellen W.} and Vilmundur Gudnason and Harris, {Tamara B.} and Hu, {Frank B.} and Hunter, {David J.} and Launer, {Lenore J.} and Andres Metspalu and Montgomery, {Grant W.} and Oostra, {Ben A.} and Ridker, {Paul M.} and Serena Sanna and David Schlessinger and Spector, {Tim D.} and Kari Stefansson and Streeten, {Elizabeth A.} and Unnur Thorsteinsdottir and Manuela Uda and Uitterlinden, {Andr{\'e} G.} and {Van Duijn}, {Cornelia M.} and Henry V{\"o}lzke and Anna Murray and Murabito, {Joanne M.} and Visser, {Jenny A.} and Lunetta, {Kathryn L.}",

year = "2012",

month = mar,

doi = "10.1038/ng.1051",

language = "English (US)",

volume = "44",

pages = "260--268",

journal = "Nature genetics",

issn = "1061-4036",

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TY - JOUR

T1 - Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

AU - Stolk, Lisette

AU - Perry, John R.B.

AU - Chasman, Daniel I.

AU - He, Chunyan

AU - Mangino, Massimo

AU - Sulem, Patrick

AU - Barbalic, Maja

AU - Broer, Linda

AU - Byrne, Enda M.

AU - Ernst, Florian

AU - Esko, Tmu

AU - Franceschini, Nora

AU - Gudbjartsson, Daniel F.

AU - Hottenga, Jouke Jan

AU - Kraft, Peter

AU - McArdle, Patrick F.

AU - Porcu, Eleonora

AU - Shin, So Youn

AU - Smith, Albert V.

AU - Van Wingerden, Sophie

AU - Zhai, Guangju

AU - Zhuang, Wei V.

AU - Albrecht, Eva

AU - Alizadeh, Behrooz Z.

AU - Aspelund, Thor

AU - Bandinelli, Stefania

AU - Lauc, Lovorka Barac

AU - Beckmann, Jacques S.

AU - Boban, Mladen

AU - Boerwinkle, Eric

AU - Broekmans, Frank J.

AU - Burri, Andrea

AU - Campbell, Harry

AU - Chanock, Stephen J.

AU - Chen, Constance

AU - Cornelis, Marilyn C.

AU - Corre, Tanguy

AU - Coviello, Andrea D.

AU - D'Adamo, Pio

AU - Davies, Gail

AU - De Faire, Ulf

AU - De Geus, Eco J.C.

AU - Deary, Ian J.

AU - Dedoussis, George V.Z.

AU - Deloukas, Panagiotis

AU - Ebrahim, Shah

AU - Eiriksdottir, Gudny

AU - Emilsson, Valur

AU - Eriksson, Johan G.

AU - Fauser, Bart C.J.M.

AU - Ferreli, Liana

AU - Ferrucci, Luigi

AU - Fischer, Krista

AU - Folsom, Aaron R.

AU - Garcia, Melissa E.

AU - Gasparini, Paolo

AU - Gieger, Christian

AU - Glazer, Nicole

AU - Grobbee, Diederick E.

AU - Hall, Per

AU - Haller, Toomas

AU - Hankinson, Susan E.

AU - Hass, Merli

AU - Hayward, Caroline

AU - Heath, Andrew C.

AU - Hofman, Albert

AU - Ingelsson, Erik

AU - Janssens, A. Cecile J.W.

AU - Johnson, Andrew D.

AU - Karasik, David

AU - Kardia, Sharon L.R.

AU - Keyzer, Jules

AU - Kiel, Douglas P.

AU - Kolcic, Ivana

AU - Kutalik, Zoltn

AU - Lahti, Jari

AU - Lai, Sandra

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AU - Laven, Joop S.E.

AU - Lawlor, Debbie A.

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AU - Lopez, Lorna M.

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AU - Magnusson, Patrik K.E.

AU - Marongiu, Mara

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AU - Klaric, Irena Martinovic

AU - Masciullo, Corrado

AU - McKnight, Barbara

AU - Medland, Sarah E.

AU - Melzer, David

AU - Mooser, Vincent

AU - Navarro, Pau

AU - Newman, Anne B.

AU - Nyholt, Dale R.

AU - Onland-Moret, N. Charlotte

AU - Palotie, Aarno

AU - Paré, Guillaume

AU - Parker, Alex N.

AU - Pedersen, Nancy L.

AU - Peeters, Petra H.M.

AU - Pistis, Giorgio

AU - Plump, Andrew S.

AU - Polasek, Ozren

AU - Pop, Victor J.M.

AU - Psaty, Bruce M.

AU - R Currency Signikkönen, Katri

AU - Rehnberg, Emil

AU - Rotter, Jerome I.

AU - Rudan, Igor

AU - Sala, Cinzia

AU - Salumets, Andres

AU - Scuteri, Angelo

AU - Singleton, Andrew

AU - Smith, Jennifer A.

AU - Snieder, Harold

AU - Soranzo, Nicole

AU - Stacey, Simon N.

AU - Starr, John M.

AU - Stathopoulou, Maria G.

AU - Stirrups, Kathleen

AU - Stolk, Ronald P.

AU - Styrkarsdottir, Unnur

AU - Sun, Yan V.

AU - Tenesa, Albert

AU - Thorand, Barbara

AU - Toniolo, Daniela

AU - Tryggvadottir, Laufey

AU - Tsui, Kim

AU - Ulivi, Sheila

AU - Van Dam, Rob M.

AU - Van Der Schouw, Yvonne T.

AU - Van Gils, Carla H.

AU - Van Nierop, Peter

AU - Vink, Jacqueline M.

AU - Visscher, Peter M.

AU - Voorhuis, Marlies

AU - Waeber, Gérard

AU - Wallaschofski, Henri

AU - Wichmann, H. Erich

AU - Widen, Elisabeth

AU - Wijnands-Van Gent, Colette J.M.

AU - Willemsen, Gonneke

AU - Wilson, James F.

AU - Wolffenbuttel, Bruce H.R.

AU - Wright, Alan F.

AU - Yerges-Armstrong, Laura M.

AU - Zemunik, Tatijana

AU - Zgaga, Lina

AU - Zillikens, M. Carola

AU - Zygmunt, Marek

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AU - Boomsma, Dorret I.

AU - Buring, Julie E.

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AU - Demerath, Ellen W.

AU - Gudnason, Vilmundur

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AU - Hu, Frank B.

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AU - Launer, Lenore J.

AU - Metspalu, Andres

AU - Montgomery, Grant W.

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AU - Uitterlinden, André G.

AU - Van Duijn, Cornelia M.

AU - Völzke, Henry

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AU - Murabito, Joanne M.

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AU - Lunetta, Kathryn L.

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AB - To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 - 10 g8). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-I °B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

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JO - Nature genetics

JF - Nature genetics

IS - 3

ER -

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

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