title: A genome-wide association study of early menopause and the combined impact of identified variants.
abstract: Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ∼30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking.
authors: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
authors: John R B
authors: JR
authors: Perry
authors: Tanguy
authors: T
authors: Corre
authors: Tõnu
authors: T
authors: Esko
authors: Daniel I
authors: DI
authors: Chasman
authors: Krista
authors: K
authors: Fischer
authors: Nora
authors: N
authors: Franceschini
authors: Chunyan
authors: C
authors: He
authors: Zoltan
authors: Z
authors: Kutalik
authors: Massimo
authors: M
authors: Mangino
authors: Lynda M
authors: LM
authors: Rose
authors: Albert
authors: A
authors: Vernon Smith
authors: Lisette
authors: L
authors: Stolk
authors: Patrick
authors: P
authors: Sulem
authors: Michael N
authors: MN
authors: Weedon
authors: Wei V
authors: WV
authors: Zhuang
authors: Alice
authors: A
authors: Arnold
authors: Alan
authors: A
authors: Ashworth
authors: Sven
authors: S
authors: Bergmann
authors: Julie E
authors: JE
authors: Buring
authors: Andrea
authors: A
authors: Burri
authors: Constance
authors: C
authors: Chen
authors: Marilyn C
authors: MC
authors: Cornelis
authors: David J
authors: DJ
authors: Couper
authors: Mark O
authors: MO
authors: Goodarzi
authors: Vilmundur
authors: V
authors: Gudnason
authors: Tamara
authors: T
authors: Harris
authors: Albert
authors: A
authors: Hofman
authors: Michael
authors: M
authors: Jones
authors: Peter
authors: P
authors: Kraft
authors: Lenore
authors: L
authors: Launer
authors: Joop S E
authors: JS
authors: Laven
authors: Guo
authors: G
authors: Li
authors: Barbara
authors: B
authors: McKnight
authors: Corrado
authors: C
authors: Masciullo
authors: Lili
authors: L
authors: Milani
authors: Nicholas
authors: N
authors: Orr
authors: Bruce M
authors: BM
authors: Psaty
authors: Paul M
authors: PM
authors: Ridker
authors: Fernando
authors: F
authors: Rivadeneira
authors: Cinzia
authors: C
authors: Sala
authors: Andres
authors: A
authors: Salumets
authors: Minouk
authors: M
authors: Schoemaker
authors: Michela
authors: M
authors: Traglia
authors: Gérard
authors: G
authors: Waeber
authors: Stephen J
authors: SJ
authors: Chanock
authors: Ellen W
authors: EW
authors: Demerath
authors: Melissa
authors: M
authors: Garcia
authors: Susan E
authors: SE
authors: Hankinson
authors: Frank B
authors: FB
authors: Hu
authors: David J
authors: DJ
authors: Hunter
authors: Kathryn L
authors: KL
authors: Lunetta
authors: Andres
authors: A
authors: Metspalu
authors: Grant W
authors: GW
authors: Montgomery
authors: Joanne M
authors: JM
authors: Murabito
authors: Anne B
authors: AB
authors: Newman
authors: Ken K
authors: KK
authors: Ong
authors: Tim D
authors: TD
authors: Spector
authors: Kari
authors: K
authors: Stefansson
authors: Anthony J
authors: AJ
authors: Swerdlow
authors: Unnur
authors: U
authors: Thorsteinsdottir
authors: Rob M
authors: RM
authors: Van Dam
authors: André G
authors: AG
authors: Uitterlinden
authors: Jenny A
authors: JA
authors: Visser
authors: Peter
authors: P
authors: Vollenweider
authors: Daniela
authors: D
authors: Toniolo
authors: Anna
authors: A
authors: Murray
mesh_terms: D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D008594:Menopause, Premature / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016649:Primary Ovarian Insufficiency / Q000235:genetics; D040641:Quantitative Trait Loci; D012306:Risk