1. Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility
- Author
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Bruno Reversade, Patrik K. E. Magnusson, Isleifur Olafsson, Stacy Steinberg, Nicholas G. Martin, Cornelis B. Lambalk, Hreinn Stefánsson, Jouke-Jan Hottenga, Kari Stefansson, Kerrie McAloney, Tim D. Spector, Scott D. Gordon, Ken K. Ong, Hilary C. Martin, Felix R. Day, Brenda W.J.H. Penninx, Gonneke Willemsen, Matt McGue, R. Alan Harris, Ragnar P. Kristjansson, Rick Jansen, Eco J. C. de Geus, Dale R. Nyholt, William G. Iacono, Dorret I. Boomsma, Grant W. Montgomery, John Perry, Michael B. Miller, Olof Sigurdardottir, Kjersti Aagaard, Robert Plomin, Hamdi Mbarek, Jaakko Kaprio, Gudmundur I. Eyjolfsson, Jacqueline M. Vink, Gareth E. Davies, Allan F. McRae, Day, Felix [0000-0003-3789-7651], Ong, Kenneth [0000-0003-4689-7530], Perry, John [0000-0001-6483-3771], Apollo - University of Cambridge Repository, Psychiatry, EMGO - Mental health, Obstetrics and gynaecology, ICaR - Ischemia and repair, Biological Psychology, EMGO+ - Quality of Care, and Center for Reproductive Medicine
- Subjects
Netherlands Twin Register (NTR) ,Male ,0301 basic medicine ,media_common.quotation_subject ,Mothers ,Fertility ,Genome-wide association study ,Single-nucleotide polymorphism ,Anxiety ,Biology ,FSHB ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,Pregnancy ,Twins, Dizygotic ,Genetics ,Humans ,Genetics(clinical) ,Family ,Longitudinal Studies ,Allele ,Genetics (clinical) ,media_common ,030219 obstetrics & reproductive medicine ,Depression ,Case-control study ,Genetic Variation ,Twin study ,3. Good health ,030104 developmental biology ,Case-Control Studies ,Menarche ,Female ,Follicle Stimulating Hormone ,Developmental Psychopathology ,Genome-Wide Association Study ,Polycystic Ovary Syndrome ,Demography - Abstract
Contains fulltext : 157507.pdf (Publisher’s version ) (Closed access) Spontaneous dizygotic (DZ) twinning occurs in 1%–4% of women, with familial clustering and unknown physiological pathways and genetic origin. DZ twinning might index increased fertility and has distinct health implications for mother and child. We performed a GWAS in 1,980 mothers of spontaneous DZ twins and 12,953 control subjects. Findings were replicated in a large Icelandic cohort and tested for association across a broad range of fertility traits in women. Two SNPs were identified (rs11031006 near FSHB, p = 1.54 × 10−9, and rs17293443 in SMAD3, p = 1.57 × 10−8) and replicated (p = 3 × 10−3 and p = 1.44 × 10−4, respectively). Based on ∼90,000 births in Iceland, the risk of a mother delivering twins increased by 18% for each copy of allele rs11031006-G and 9% for rs17293443-C. A higher polygenic risk score (PRS) for DZ twinning, calculated based on the results of the DZ twinning GWAS, was significantly associated with DZ twinning in Iceland (p = 0.001). A higher PRS was also associated with having children (p = 0.01), greater lifetime parity (p = 0.03), and earlier age at first child (p = 0.02). Allele rs11031006-G was associated with higher serum FSH levels, earlier age at menarche, earlier age at first child, higher lifetime parity, lower PCOS risk, and earlier age at menopause. Conversely, rs17293443-C was associated with later age at last child. We identified robust genetic risk variants for DZ twinning: one near FSHB and a second within SMAD3, the product of which plays an important role in gonadal responsiveness to FSH. These loci contribute to crucial aspects of reproductive capacity and health. 11 p.
- Published
- 2016