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(-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.
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Lisette
authors.initials: L
authors.lastname: Stolk
authors.forename: John R B
authors.initials: JR
authors.lastname: Perry
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.forename: Chunyan
authors.initials: C
authors.lastname: He
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.forename: Maja
authors.initials: M
authors.lastname: Barbalic
authors.forename: Linda
authors.initials: L
authors.lastname: Broer
authors.forename: Enda M
authors.initials: EM
authors.lastname: Byrne
authors.forename: Florian
authors.initials: F
authors.lastname: Ernst
authors.forename: Tõnu
authors.initials: T
authors.lastname: Esko
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Patrick F
authors.initials: PF
authors.lastname: McArdle
authors.forename: Eleonora
authors.initials: E
authors.lastname: Porcu
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Shin
authors.forename: Albert V
authors.initials: AV
authors.lastname: Smith
authors.forename: Sophie
authors.initials: S
authors.lastname: van Wingerden
authors.forename: Guangju
authors.initials: G
authors.lastname: Zhai
authors.forename: Wei V
authors.initials: WV
authors.lastname: Zhuang
authors.forename: Eva
authors.initials: E
authors.lastname: Albrecht
authors.forename: Behrooz Z
authors.initials: BZ
authors.lastname: Alizadeh
authors.forename: Thor
authors.initials: T
authors.lastname: Aspelund
authors.forename: Stefania
authors.initials: S
authors.lastname: Bandinelli
authors.forename: Lovorka Barac
authors.initials: LB
authors.lastname: Lauc
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Mladen
authors.initials: M
authors.lastname: Boban
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Broekmans
authors.forename: Andrea
authors.initials: A
authors.lastname: Burri
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Constance
authors.initials: C
authors.lastname: Chen
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Cornelis
authors.forename: Tanguy
authors.initials: T
authors.lastname: Corre
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Coviello
authors.forename: Pio
authors.initials: P
authors.lastname: d'Adamo
authors.forename: Gail
authors.initials: G
authors.lastname: Davies
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.forename: George V Z
authors.initials: GV
authors.lastname: Dedoussis
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Deloukas
authors.forename: Shah
authors.initials: S
authors.lastname: Ebrahim
authors.forename: Gudny
authors.initials: G
authors.lastname: Eiriksdottir
authors.forename: Valur
authors.initials: V
authors.lastname: Emilsson
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.forename: Bart C J M
authors.initials: BC
authors.lastname: Fauser
authors.forename: Liana
authors.initials: L
authors.lastname: Ferreli
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Krista
authors.initials: K
authors.lastname: Fischer
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Garcia
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Nicole
authors.initials: N
authors.lastname: Glazer
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Per
authors.initials: P
authors.lastname: Hall
authors.forename: Toomas
authors.initials: T
authors.lastname: Haller
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Merli
authors.initials: M
authors.lastname: Hass
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Heath
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
authors.forename: A Cecile J W
authors.initials: AC
authors.lastname: Janssens
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Johnson
authors.forename: David
authors.initials: D
authors.lastname: Karasik
authors.forename: Sharon L R
authors.initials: SL
authors.lastname: Kardia
authors.forename: Jules
authors.initials: J
authors.lastname: Keyzer
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Kiel
authors.forename: Ivana
authors.initials: I
authors.lastname: Kolcic
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kutalik
authors.forename: Jari
authors.initials: J
authors.lastname: Lahti
authors.forename: Sandra
authors.initials: S
authors.lastname: Lai
authors.forename: Triin
authors.initials: T
authors.lastname: Laisk
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.forename: Lorna M
authors.initials: LM
authors.lastname: Lopez
authors.forename: Yvonne V
authors.initials: YV
authors.lastname: Louwers
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.forename: Mara
authors.initials: M
authors.lastname: Marongiu
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Irena Martinovic
authors.initials: IM
authors.lastname: Klaric
authors.forename: Corrado
authors.initials: C
authors.lastname: Masciullo
authors.forename: Barbara
authors.initials: B
authors.lastname: McKnight
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Medland
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.forename: Vincent
authors.initials: V
authors.lastname: Mooser
authors.forename: Pau
authors.initials: P
authors.lastname: Navarro
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.forename: Dale R
authors.initials: DR
authors.lastname: Nyholt
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Guillaume
authors.initials: G
authors.lastname: Paré
authors.forename: Alex N
authors.initials: AN
authors.lastname: Parker
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pistis
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Plump
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: Victor J M
authors.initials: VJ
authors.lastname: Pop
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Katri
authors.initials: K
authors.lastname: Räikkönen
authors.forename: Emil
authors.initials: E
authors.lastname: Rehnberg
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Cinzia
authors.initials: C
authors.lastname: Sala
authors.forename: Andres
authors.initials: A
authors.lastname: Salumets
authors.forename: Angelo
authors.initials: A
authors.lastname: Scuteri
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Smith
authors.forename: Harold
authors.initials: H
authors.lastname: Snieder
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Simon N
authors.initials: SN
authors.lastname: Stacey
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.forename: Maria G
authors.initials: MG
authors.lastname: Stathopoulou
authors.forename: Kathleen
authors.initials: K
authors.lastname: Stirrups
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Stolk
authors.forename: Unnur
authors.initials: U
authors.lastname: Styrkarsdottir
authors.forename: Yan V
authors.initials: YV
authors.lastname: Sun
authors.forename: Albert
authors.initials: A
authors.lastname: Tenesa
authors.forename: Barbara
authors.initials: B
authors.lastname: Thorand
authors.forename: Daniela
authors.initials: D
authors.lastname: Toniolo
authors.forename: Laufey
authors.initials: L
authors.lastname: Tryggvadottir
authors.forename: Kim
authors.initials: K
authors.lastname: Tsui
authors.forename: Sheila
authors.initials: S
authors.lastname: Ulivi
authors.forename: Rob M
authors.initials: RM
authors.lastname: van Dam
authors.forename: Yvonne T
authors.initials: YT
authors.lastname: van der Schouw
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
authors.forename: Peter
authors.initials: P
authors.lastname: van Nierop
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Vink
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
authors.forename: Marlies
authors.initials: M
authors.lastname: Voorhuis
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.forename: Henri
authors.initials: H
authors.lastname: Wallaschofski
authors.forename: H Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Widen
authors.forename: Colette J M
authors.initials: CJ
authors.lastname: Wijnands-van Gent
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Laura M
authors.initials: LM
authors.lastname: Yerges-Armstrong
authors.forename: Tatijana
authors.initials: T
authors.lastname: Zemunik
authors.forename: Lina
authors.initials: L
authors.lastname: Zgaga
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
authors.forename: Marek
authors.initials: M
authors.lastname: Zygmunt
authors.forename: Alice M
authors.initials: AM
authors.lastname: Arnold
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.forename: Laura
authors.initials: L
authors.lastname: Crisponi
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Demerath
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Streeten
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Manuela
authors.initials: M
authors.lastname: Uda
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Anna
authors.initials: A
authors.lastname: Murray
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Murabito
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Visser
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lunetta
mesh_terms: D000367:Age Factors; D004265:DNA Helicases / Q000235:genetics; D000074002:DNA Polymerase gamma; D019915:DNA Primase / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D007109:Immunity / Q000235:genetics*; D008593:Menopause / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D011506:Proteins; C092008:PRRC2A protein, human; D019915:DNA Primase; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; C451406:HELQ protein, human; D045643:DNA Repair Enzymes