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

L. Stolk; J.R.B. Perry; D.I. Chasman; C. He; M. Mangino; P. Sulem; M. Barbalic; L. Broer; E.M. Byrne; F. Ernst; T. Esko; N. Franceschini; D.F. Gudbjartsson; J.J. Hottenga; P. Kraft; P.F. McArdle; E. Porcu; S.Y. Shin; A.V. Smith; S. van Wingerden; G. Zhai; W.V. Zhuang; E. Albrecht; BZ Alizadeh; T. Aspelund; E.J.C. de Geus; J.M. Vink; G. Willemsen; D.I. Boomsma; L. Crisponi; E.W. Demerath; V. Gudnason; T.B. Harris; F.B. Hu; D.J. Hunter; L.J. Launer; A. Metspalu; G.W. Montgomery; B.A. Oostra; P.M. Ridker; S. Sanna; D. Schlessinger; T.D. Spector; K. Stefansson; E.A. Streeten; U. Thorsteinsdottir; M. Uda; A.G. Uitterlinden; C.M. van Duijn; H. Völzke; A. Murray; J.M. Murabito; J.A. Visser; K.L. Lunetta

doi:10.1038/ng.1051

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

L. Stolk, J.R.B. Perry, D.I. Chasman, C. He, M. Mangino, P. Sulem, M. Barbalic, L. Broer, E.M. Byrne, F. Ernst, T. Esko, N. Franceschini, D.F. Gudbjartsson, J.J. Hottenga, P. Kraft, P.F. McArdle, E. Porcu, S.Y. Shin, A.V. Smith, S. van WingerdenG. Zhai, W.V. Zhuang, E. Albrecht, BZ Alizadeh, T. Aspelund, E.J.C. de Geus, J.M. Vink, G. Willemsen, D.I. Boomsma, L. Crisponi, E.W. Demerath, V. Gudnason, T.B. Harris, F.B. Hu, D.J. Hunter, L.J. Launer, A. Metspalu, G.W. Montgomery, B.A. Oostra, P.M. Ridker, S. Sanna, D. Schlessinger, T.D. Spector, K. Stefansson, E.A. Streeten, U. Thorsteinsdottir, M. Uda, A.G. Uitterlinden, C.M. van Duijn, H. Völzke, A. Murray, J.M. Murabito, J.A. Visser, K.L. Lunetta

Biological Psychology

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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. © 2012 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	260-268
Journal	Nature Genetics
Volume	44
Issue number	3
DOIs	https://doi.org/10.1038/ng.1051
Publication status	Published - 2012

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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

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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. {\textcopyright} 2012 Nature America, Inc. All rights reserved.",

author = "L. Stolk and J.R.B. Perry and D.I. Chasman and C. He and M. Mangino and P. Sulem and M. Barbalic and L. Broer and E.M. Byrne and F. Ernst and T. Esko and N. Franceschini and D.F. Gudbjartsson and J.J. Hottenga and P. Kraft and P.F. McArdle and E. Porcu and S.Y. Shin and A.V. Smith and \{van Wingerden\}, S. and G. Zhai and W.V. Zhuang and E. Albrecht and BZ Alizadeh and T. Aspelund and \{de Geus\}, E.J.C. and J.M. Vink and G. Willemsen and D.I. Boomsma and L. Crisponi and E.W. Demerath and V. Gudnason and T.B. Harris and F.B. Hu and D.J. Hunter and L.J. Launer and A. Metspalu and G.W. Montgomery and B.A. Oostra and P.M. Ridker and S. Sanna and D. Schlessinger and T.D. Spector and K. Stefansson and E.A. Streeten and U. Thorsteinsdottir and M. Uda and A.G. Uitterlinden and \{van Duijn\}, C.M. and H. V{\"o}lzke and A. Murray and J.M. Murabito and J.A. Visser and K.L. Lunetta",

year = "2012",

doi = "10.1038/ng.1051",

language = "English",

volume = "44",

pages = "260--268",

journal = "Nature Genetics",

issn = "1061-4036",

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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, de Geus, EJC, Vink, JM, Willemsen, G, Boomsma, DI, 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

TY - JOUR

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

AU - Stolk, L.

AU - Perry, J.R.B.

AU - Chasman, D.I.

AU - He, C.

AU - Mangino, M.

AU - Sulem, P.

AU - Barbalic, M.

AU - Broer, L.

AU - Byrne, E.M.

AU - Ernst, F.

AU - Esko, T.

AU - Franceschini, N.

AU - Gudbjartsson, D.F.

AU - Hottenga, J.J.

AU - Kraft, P.

AU - McArdle, P.F.

AU - Porcu, E.

AU - Shin, S.Y.

AU - Smith, A.V.

AU - van Wingerden, S.

AU - Zhai, G.

AU - Zhuang, W.V.

AU - Albrecht, E.

AU - Alizadeh, BZ

AU - Aspelund, T.

AU - de Geus, E.J.C.

AU - Vink, J.M.

AU - Willemsen, G.

AU - Boomsma, D.I.

AU - Crisponi, L.

AU - Demerath, E.W.

AU - Gudnason, V.

AU - Harris, T.B.

AU - Hu, F.B.

AU - Hunter, D.J.

AU - Launer, L.J.

AU - Metspalu, A.

AU - Montgomery, G.W.

AU - Oostra, B.A.

AU - Ridker, P.M.

AU - Sanna, S.

AU - Schlessinger, D.

AU - Spector, T.D.

AU - Stefansson, K.

AU - Streeten, E.A.

AU - Thorsteinsdottir, U.

AU - Uda, M.

AU - Uitterlinden, A.G.

AU - van Duijn, C.M.

AU - Völzke, H.

AU - Murray, A.

AU - Murabito, J.M.

AU - Visser, J.A.

AU - Lunetta, K.L.

PY - 2012

Y1 - 2012

N2 - 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. © 2012 Nature America, Inc. All rights reserved.

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. © 2012 Nature America, Inc. All rights reserved.

UR - https://www.scopus.com/pages/publications/84862777492

UR - https://www.scopus.com/inward/citedby.url?scp=84862777492&partnerID=8YFLogxK

U2 - 10.1038/ng.1051

DO - 10.1038/ng.1051

M3 - Article

SN - 1061-4036

VL - 44

SP - 260

EP - 268

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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