Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
27132594
TITLE
Identification of Common Genetic Variants Influencing Spontaneous Dizygotic Twinning and Female Fertility.
ABSTRACT
NlmCategory: UNASSIGNED
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.
Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2016 Apr 27
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/01/11
accepted 2016/03/14
entrez 2016/05/03 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Mbarek H Mbarek Hamdi H Department of Biological Psychology, Vrije Universiteit, 1081BT Amsterdam, the Netherlands; EMGO+ Institute for Health and Care Research, 1081BT Amsterdam, the Netherlands. Electronic address: h.mbarek@vu.nl.
Steinberg S Steinberg Stacy S deCODE Genetics, 101 Reykjavik, Iceland.
Nyholt DR Nyholt Dale R DR Institute of Health and Biomedical Innovation, Queensland University of Technology, 4059 Brisbane, Australia; QIMR Berghofer Medical Research Institute, 4029 Brisbane, Australia.
Gordon SD Gordon Scott D SD QIMR Berghofer Medical Research Institute, 4029 Brisbane, Australia.
Miller MB Miller Michael B MB Department of Psychology, University of Minnesota, Minneapolis, MN 55455, USA.
McRae AF McRae Allan F AF QIMR Berghofer Medical Research Institute, 4029 Brisbane, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
Hottenga JJ Hottenga Jouke Jan JJ Department of Biological Psychology, Vrije Universiteit, 1081BT Amsterdam, the Netherlands; EMGO+ Institute for Health and Care Research, 1081BT Amsterdam, the Netherlands.
Day FR Day Felix R FR MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Willemsen G Willemsen Gonneke G Department of Biological Psychology, Vrije Universiteit, 1081BT Amsterdam, the Netherlands; EMGO+ Institute for Health and Care Research, 1081BT Amsterdam, the Netherlands.
de Geus EJ de Geus Eco J EJ Department of Biological Psychology, Vrije Universiteit, 1081BT Amsterdam, the Netherlands; EMGO+ Institute for Health and Care Research, 1081BT Amsterdam, the Netherlands.
Davies GE Davies Gareth E GE Avera Institute for Human Genetics, Sioux Falls, SD 57108, USA.
Martin HC Martin Hilary C HC Wellcome Trust Centre for Human Genetics, Oxford OX3 TBN, UK.
Penninx BW Penninx Brenda W BW Department of Psychiatry and EMGO Institute for Health and Care Research, Vrije U Universiteit, Medical Center/GGZ inGeest, 1081HL Amsterdam, the Netherlands.
Jansen R Jansen Rick R Department of Psychiatry and EMGO Institute for Health and Care Research, Vrije U Universiteit, Medical Center/GGZ inGeest, 1081HL Amsterdam, the Netherlands.
McAloney K McAloney Kerrie K QIMR Berghofer Medical Research Institute, 4029 Brisbane, Australia.
Vink JM Vink Jacqueline M JM Department of Biological Psychology, Vrije Universiteit, 1081BT Amsterdam, the Netherlands.
Kaprio J Kaprio Jaakko J Institute for Molecular Medicine Finland FIMM, University of Helsinki; Department of Public Health, University of Helsinki; National Institute for Health and Welfare, 00014 Helsinki, Finland.
Plomin R Plomin Robert R Medical Research Council Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK.
Spector TD Spector Tim D TD Department of Twin Research & Genetic Epidemiology, King's College London, London SE1 7EH, UK.
Magnusson PK Magnusson Patrik K PK Department of Medical Epidemiology and Biostatistics, Karolinska Institute, 171 77 Stockholm, Sweden.
Reversade B Reversade Bruno B Institute of Medical Biology, Laboratory of Human Genetics and Embryology, A(∗)STAR, 138648 Singapore, Singapore; Amsterdam Reproduction & Development, Academic Medical Centre, Reproductive Biology Laboratory (Q3-119), Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Department of Obstetrics, Gynecology and Reproductive Medicine, VU University Medical Center, 1007MB Amsterdam, the Netherlands.
Harris RA Harris R Alan RA Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology, Molecular and Human Genetics, and Molecular and Cell Biology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030, USA.
Aagaard K Aagaard Kjersti K Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology, Molecular and Human Genetics, and Molecular and Cell Biology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX 77030, USA.
Kristjansson RP Kristjansson Ragnar P RP deCODE Genetics, 101 Reykjavik, Iceland.
Olafsson I Olafsson Isleifur I Department of Clinical Biochemistry, Landspitali-The National University Hospital of Iceland, 101 Reykjavik, Iceland.
Eyjolfsson GI Eyjolfsson Gudmundur Ingi GI Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM), 101 Reykjavik, Iceland.
Sigurdardottir O Sigurdardottir Olof O Department of Clinical Biochemistry, Akureyri Hospital, 109 Akureyri, Iceland.
Iacono WG Iacono William G WG Department of Psychology, University of Minnesota, Minneapolis, MN 55455, USA.
Lambalk CB Lambalk Cornelis B CB Department of Obstetrics, Gynecology and Reproductive Medicine, VU University Medical Center, 1007MB Amsterdam, the Netherlands.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, 4029 Brisbane, Australia.
McGue M McGue Matt M Department of Psychology, University of Minnesota, Minneapolis, MN 55455, USA.
Ong KK Ong Ken K KK MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Perry JR Perry John R B JR MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, 4029 Brisbane, Australia.
Stefánsson H Stefánsson Hreinn H deCODE Genetics, 101 Reykjavik, Iceland.
Stefánsson K Stefánsson Kari K deCODE Genetics, 101 Reykjavik, Iceland.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, Vrije Universiteit, 1081BT Amsterdam, the Netherlands; EMGO+ Institute for Health and Care Research, 1081BT Amsterdam, the Netherlands. Electronic address: di.boomsma@vu.nl.
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JOURNAL
VOLUME:
ISSUE:
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2016
MONTH: Apr
DAY: 27
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1537-6605
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
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PUBLICATIONTYPE TEXT
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