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 | |
| State | Published - Mar 2012 |
All Science Journal Classification (ASJC) codes
- Genetics
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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. / Stolk, Lisette; Perry, John R.B.; Chasman, Daniel I.; He, Chunyan; Mangino, Massimo; Sulem, Patrick; Barbalic, Maja; Broer, Linda; Byrne, Enda M.; Ernst, Florian; Esko, Tmu; Franceschini, Nora; Gudbjartsson, Daniel F.; Hottenga, Jouke Jan; Kraft, Peter; McArdle, Patrick F.; Porcu, Eleonora; Shin, So Youn; Smith, Albert V.; Van Wingerden, Sophie; Zhai, Guangju; Zhuang, Wei V.; Albrecht, Eva; Alizadeh, Behrooz Z.; Aspelund, Thor; Bandinelli, Stefania; Lauc, Lovorka Barac; Beckmann, Jacques S.; Boban, Mladen; Boerwinkle, Eric; Broekmans, Frank J.; Burri, Andrea; Campbell, Harry; Chanock, Stephen J.; Chen, Constance; Cornelis, Marilyn C.; Corre, Tanguy; Coviello, Andrea D.; D'Adamo, Pio; Davies, Gail; De Faire, Ulf; De Geus, Eco J.C.; Deary, Ian J.; Dedoussis, George V.Z.; Deloukas, Panagiotis; Ebrahim, Shah; Eiriksdottir, Gudny; Emilsson, Valur; Eriksson, Johan G.; Fauser, Bart C.J.M.; Ferreli, Liana; Ferrucci, Luigi; Fischer, Krista; Folsom, Aaron R.; Garcia, Melissa E.; Gasparini, Paolo; Gieger, Christian; Glazer, Nicole; Grobbee, Diederick E.; Hall, Per; Haller, Toomas; Hankinson, Susan E.; Hass, Merli; Hayward, Caroline; Heath, Andrew C.; Hofman, Albert; Ingelsson, Erik; Janssens, A. Cecile J.W.; Johnson, Andrew D.; Karasik, David; Kardia, Sharon L.R.; Keyzer, Jules; Kiel, Douglas P.; Kolcic, Ivana; Kutalik, Zoltn; Lahti, Jari; Lai, Sandra; Laisk, Triin; Laven, Joop S.E.; Lawlor, Debbie A.; Liu, Jianjun; Lopez, Lorna M.; Louwers, Yvonne V.; Magnusson, Patrik K.E.; Marongiu, Mara; Martin, Nicholas G.; Klaric, Irena Martinovic; Masciullo, Corrado; McKnight, Barbara; Medland, Sarah E.; Melzer, David; Mooser, Vincent; Navarro, Pau; Newman, Anne B.; Nyholt, Dale R.; Onland-Moret, N. Charlotte; Palotie, Aarno; Paré, Guillaume; Parker, Alex N.; Pedersen, Nancy L.; Peeters, Petra H.M.; Pistis, Giorgio; Plump, Andrew S.; Polasek, Ozren; Pop, Victor J.M.; Psaty, Bruce M.; R Currency Signikkönen, Katri; Rehnberg, Emil; Rotter, Jerome I.; Rudan, Igor; Sala, Cinzia; Salumets, Andres; Scuteri, Angelo; Singleton, Andrew; Smith, Jennifer A.; Snieder, Harold; Soranzo, Nicole; Stacey, Simon N.; Starr, John M.; Stathopoulou, Maria G.; Stirrups, Kathleen; Stolk, Ronald P.; Styrkarsdottir, Unnur; Sun, Yan V.; Tenesa, Albert; Thorand, Barbara; Toniolo, Daniela; Tryggvadottir, Laufey; Tsui, Kim; Ulivi, Sheila; Van Dam, Rob M.; Van Der Schouw, Yvonne T.; Van Gils, Carla H.; Van Nierop, Peter; Vink, Jacqueline M.; Visscher, Peter M.; Voorhuis, Marlies; Waeber, Gérard; Wallaschofski, Henri; Wichmann, H. Erich; Widen, Elisabeth; Wijnands-Van Gent, Colette J.M.; Willemsen, Gonneke; Wilson, James F.; Wolffenbuttel, Bruce H.R.; Wright, Alan F.; Yerges-Armstrong, Laura M.; Zemunik, Tatijana; Zgaga, Lina; Zillikens, M. Carola; Zygmunt, Marek; Arnold, Alice M.; Boomsma, Dorret I.; Buring, Julie E.; Crisponi, Laura; Demerath, Ellen W.; Gudnason, Vilmundur; Harris, Tamara B.; Hu, Frank B.; Hunter, David J.; Launer, Lenore J.; Metspalu, Andres; Montgomery, Grant W.; Oostra, Ben A.; Ridker, Paul M.; Sanna, Serena; Schlessinger, David; Spector, Tim D.; Stefansson, Kari; Streeten, Elizabeth A.; Thorsteinsdottir, Unnur; Uda, Manuela; Uitterlinden, André G.; Van Duijn, Cornelia M.; Völzke, Henry; Murray, Anna; Murabito, Joanne M.; Visser, Jenny A.; Lunetta, Kathryn L.
In: Nature genetics, Vol. 44, No. 3, 03.2012, p. 260-268.Research output: Contribution to journal › Article › peer-review
}
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
AU - Laisk, Triin
AU - Laven, Joop S.E.
AU - Lawlor, Debbie A.
AU - Liu, Jianjun
AU - Lopez, Lorna M.
AU - Louwers, Yvonne V.
AU - Magnusson, Patrik K.E.
AU - Marongiu, Mara
AU - Martin, Nicholas G.
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
AU - Arnold, Alice M.
AU - Boomsma, Dorret I.
AU - Buring, Julie E.
AU - Crisponi, Laura
AU - Demerath, Ellen W.
AU - Gudnason, Vilmundur
AU - Harris, Tamara B.
AU - Hu, Frank B.
AU - Hunter, David J.
AU - Launer, Lenore J.
AU - Metspalu, Andres
AU - Montgomery, Grant W.
AU - Oostra, Ben A.
AU - Ridker, Paul M.
AU - Sanna, Serena
AU - Schlessinger, David
AU - Spector, Tim D.
AU - Stefansson, Kari
AU - Streeten, Elizabeth A.
AU - Thorsteinsdottir, Unnur
AU - Uda, Manuela
AU - Uitterlinden, André G.
AU - Van Duijn, Cornelia M.
AU - Völzke, Henry
AU - Murray, Anna
AU - Murabito, Joanne M.
AU - Visser, Jenny A.
AU - Lunetta, Kathryn L.
PY - 2012/3
Y1 - 2012/3
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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84862777492&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862777492&partnerID=8YFLogxK
U2 - 10.1038/ng.1051
DO - 10.1038/ng.1051
M3 - Article
C2 - 22267201
AN - SCOPUS:84862777492
VL - 44
SP - 260
EP - 268
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 3
ER -