OBJECTIVE: Existing estimates of the heritability of menopause age have a wide range. Furthermore, few studies have analyzed to what extent familial similarities might reflect shared environment, rather than shared genes. We therefore analyzed familial concordance for age at natural menopause and the effects of shared genetic and environmental factors on this concordance. METHODS: Participants were 2,060 individuals comprising first-degree relatives, aged 31 to 90 years, and participating in the UK Breakthrough Generations Study. Menopause data were collected using a self-administered questionnaire and analyzed using logistic regression and variance-components models. RESULTS: Women were at an increased risk of early menopause (≤45 y) if their mother (odds ratio, 6.2; P < 0.001) or non-twin sister (odds ratio, 5.5; P < 0.001) had had an early menopause. Likewise, women had an increased risk of late menopause (≥54 y) if their relative had had a late menopause (mother: odds ratio, 6.1; P < 0.01; non-twin sister: odds ratio, 2.3; P < 0.001). Estimated heritability was 41.6% (P < 0.01), with an additional 13.6% (P = 0.02) of the variation in menopause age attributed to environmental factors shared by sisters. CONCLUSIONS: We confirm that early menopause aggregates within families and show, for the first time, that there is also strong familial concordance for late menopause. Both genes and shared environment were the source of variation in menopause age. Past heritability estimates have not accounted for shared environment, and thus, the effect of genetic variants on menopause age may previously have been overestimated.
OBJECTIVE: Existing estimates of the heritability of menopause age have a wide range. Furthermore, few studies have analyzed to what extent familial similarities might reflect shared environment, rather than shared genes. We therefore analyzed familial concordance for age at natural menopause and the effects of shared genetic and environmental factors on this concordance. METHODS: Participants were 2,060 individuals comprising first-degree relatives, aged 31 to 90 years, and participating in the UK Breakthrough Generations Study. Menopause data were collected using a self-administered questionnaire and analyzed using logistic regression and variance-components models. RESULTS: Women were at an increased risk of early menopause (≤45 y) if their mother (odds ratio, 6.2; P < 0.001) or non-twin sister (odds ratio, 5.5; P < 0.001) had had an early menopause. Likewise, women had an increased risk of late menopause (≥54 y) if their relative had had a late menopause (mother: odds ratio, 6.1; P < 0.01; non-twin sister: odds ratio, 2.3; P < 0.001). Estimated heritability was 41.6% (P < 0.01), with an additional 13.6% (P = 0.02) of the variation in menopause age attributed to environmental factors shared by sisters. CONCLUSIONS: We confirm that early menopause aggregates within families and show, for the first time, that there is also strong familial concordance for late menopause. Both genes and shared environment were the source of variation in menopause age. Past heritability estimates have not accounted for shared environment, and thus, the effect of genetic variants on menopause age may previously have been overestimated.
Authors: C L Carty; K L Spencer; V W Setiawan; L Fernandez-Rhodes; J Malinowski; S Buyske; A Young; N W Jorgensen; I Cheng; C S Carlson; K Brown-Gentry; R Goodloe; A Park; N I Parikh; B Henderson; L Le Marchand; J Wactawski-Wende; M Fornage; T C Matise; L A Hindorff; A M Arnold; C A Haiman; N Franceschini; U Peters; D C Crawford Journal: Hum Reprod Date: 2013-03-18 Impact factor: 6.918
Authors: Christina T L Chen; Ching-Ti Liu; Gary K Chen; Jeanette S Andrews; Alice M Arnold; Jill Dreyfus; Nora Franceschini; Melissa E Garcia; Kathleen F Kerr; Guo Li; Kurt K Lohman; Solomon K Musani; Michael A Nalls; Leslie J Raffel; Jennifer Smith; Christine B Ambrosone; Elisa V Bandera; Leslie Bernstein; Angela Britton; Robert G Brzyski; Anne Cappola; Christopher S Carlson; David Couper; Sandra L Deming; Mark O Goodarzi; Gerardo Heiss; Esther M John; Xiaoning Lu; Loic Le Marchand; Kristin Marciante; Barbara Mcknight; Robert Millikan; Nora L Nock; Andrew F Olshan; Michael F Press; Dhananjay Vaiyda; Nancy F Woods; Herman A Taylor; Wei Zhao; Wei Zheng; Michele K Evans; Tamara B Harris; Brian E Henderson; Sharon L R Kardia; Charles Kooperberg; Yongmei Liu; Thomas H Mosley; Bruce Psaty; Melissa Wellons; Beverly G Windham; Alan B Zonderman; L Adrienne Cupples; Ellen W Demerath; Christopher Haiman; Joanne M Murabito; Aleksandar Rajkovic Journal: Hum Mol Genet Date: 2014-02-02 Impact factor: 6.150
Authors: Abigail Fraser; William McNally; Naveed Sattar; Emma L Anderson; Hany Lashen; Richard Fleming; Debbie A Lawlor; Scott M Nelson Journal: Am J Epidemiol Date: 2013-09-05 Impact factor: 4.897
Authors: John R B Perry; Tanguy Corre; Tõnu Esko; Daniel I Chasman; Krista Fischer; Nora Franceschini; Chunyan He; Zoltan Kutalik; Massimo Mangino; Lynda M Rose; Albert Vernon Smith; Lisette Stolk; Patrick Sulem; Michael N Weedon; Wei V Zhuang; Alice Arnold; Alan Ashworth; Sven Bergmann; Julie E Buring; Andrea Burri; Constance Chen; Marilyn C Cornelis; David J Couper; Mark O Goodarzi; Vilmundur Gudnason; Tamara Harris; Albert Hofman; Michael Jones; Peter Kraft; Lenore Launer; Joop S E Laven; Guo Li; Barbara McKnight; Corrado Masciullo; Lili Milani; Nicholas Orr; Bruce M Psaty; Paul M Ridker; Fernando Rivadeneira; Cinzia Sala; Andres Salumets; Minouk Schoemaker; Michela Traglia; Gérard Waeber; Stephen J Chanock; Ellen W Demerath; Melissa Garcia; Susan E Hankinson; Frank B Hu; David J Hunter; Kathryn L Lunetta; Andres Metspalu; Grant W Montgomery; Joanne M Murabito; Anne B Newman; Ken K Ong; Tim D Spector; Kari Stefansson; Anthony J Swerdlow; Unnur Thorsteinsdottir; Rob M Van Dam; André G Uitterlinden; Jenny A Visser; Peter Vollenweider; Daniela Toniolo; Anna Murray Journal: Hum Mol Genet Date: 2013-01-09 Impact factor: 6.150