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

by Emilsson, Valur , Pistis, Giorgio , Broer, Linda , Boomsma, Dorret I , Eriksson, Johan G , Zygmunt, Marek , Räikkönen, Katri , Crisponi, Laura , Onland-Moret, N Charlotte , Toniolo, Daniela , de Faire, Ulf , Gudnason, Vilmundur , Streeten, Elizabeth A , Rotter, Jerome I , Porcu, Eleonora , McKnight, Barbara , Harris, Tamara B , Sanna, Serena , Franceschini, Nora , Stolk, Lisette , Zemunik, Tatijana , Ebrahim, Shah , Montgomery, Grant W , Peeters, Petra H M , Chen, Constance , Zgaga, Lina , Tenesa, Albert , Rudan, Igor , Eiriksdottir, Gudny , Plump, Andrew S , Stefansson, Kari , Alizadeh, Behrooz Z , Newman, Anne B , Gasparini, Paolo , Hall, Per , Louwers, Yvonne V , van der Schouw, Yvonne T , Kardia, Sharon L R , Thorand, Barbara , Pedersen, Nancy L , Esko, Tõnu , Parker, Alex N , Kraft, Peter , Broekmans, Frank J , Navarro, Pau , Soranzo, Nicole , Wilson, James F , Hayward, Caroline , Wichmann, H Erich , Masciullo, Corrado , Hu, Frank B , Sun, Yan V , Uitterlinden, André G , Campbell, Harry , Stathopoulou, Maria G , Murray, Anna , Folsom, Aaron R , van Dam, Rob M , Lawlor, Debbie A , Waeber, Gérard , Davies, Gail , Garcia, Melissa E , Boerwinkle, Eric , Tsui, Kim , Gudbjar

in 631/208/205/2138 / 631/208/248 / 631/337/1427 / 631/443/494 / Age Factors / Aging / Agriculture / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Breast cancer / Cancer Research / Deoxyribonucleic acid / DNA / DNA Helicases - genetics / DNA Polymerase gamma / DNA Primase - genetics / DNA repair / DNA Repair - genetics / DNA Repair Enzymes - genetics / DNA-Directed DNA Polymerase - genetics / Exodeoxyribonucleases - genetics / Female / Fundamental and applied biological sciences. Psychology / Gene Function / Genes / Genetic aspects / Genetic Loci - genetics / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study / Genomes / Human Genetics / Humans / Immune complexes / Immune response / Immunity - genetics / Menopause / Menopause - genetics / Menopause - physiology / Molecular and cellular biology / Molecular genetics / Mutagenesis. Repair / Mutation / Physiological aspects / Polymorphism, Single Nucleotide - genetics / Proteins - genetics / Studies / White People - genetics / Womens health

2012

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

2012

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2012

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Journal Article

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

Emilsson, Valur,

Pistis, Giorgio,

Broer, Linda,

Boomsma, Dorret I,

Eriksson, Johan G,

Zygmunt, Marek,

Räikkönen, Katri,

Crisponi, Laura,

Onland-Moret, N Charlotte,

Toniolo, Daniela,

de Faire, Ulf,

Gudnason, Vilmundur,

Streeten, Elizabeth A,

Rotter, Jerome I,

Porcu, Eleonora,

McKnight, Barbara,

Harris, Tamara B,

Sanna, Serena,

Franceschini, Nora,

Stolk, Lisette,

Zemunik, Tatijana,

Ebrahim, Shah,

Montgomery, Grant W,

Peeters, Petra H M,

Chen, Constance,

Zgaga, Lina,

Tenesa, Albert,

Rudan, Igor,

Eiriksdottir, Gudny,

Plump, Andrew S,

Stefansson, Kari,

Alizadeh, Behrooz Z,

Newman, Anne B,

Gasparini, Paolo,

Hall, Per,

Louwers, Yvonne V,

van der Schouw, Yvonne T,

Kardia, Sharon L R,

Thorand, Barbara,

Pedersen, Nancy L,

Esko, Tõnu,

Parker, Alex N,

Kraft, Peter,

Broekmans, Frank J,

Navarro, Pau,

Soranzo, Nicole,

Wilson, James F,

Hayward, Caroline,

Wichmann, H Erich,

Masciullo, Corrado,

Hu, Frank B,

Sun, Yan V,

Uitterlinden, André G,

Campbell, Harry,

Stathopoulou, Maria G,

Murray, Anna,

Folsom, Aaron R,

van Dam, Rob M,

Lawlor, Debbie A,

Waeber, Gérard,

Davies, Gail,

Garcia, Melissa E,

Boerwinkle, Eric,

Tsui, Kim,

Gudbjar

2012

Overview

Kathryn Lunetta and colleagues report a meta-analysis of 22 genome-wide association studies for age at menopause. They identify 13 loci newly associated with age at natural menopause, including several candidate genes with roles in DNA repair and immune function. 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 −8 ). 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-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

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Publisher

Nature Publishing Group US,Nature Publishing Group

Subject

/ Aging