Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility
This article is free to read at the publisher's website 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 c...
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ftqueensland:oai:eprints.qut.edu.au:222074 2024-01-28T10:06:40+01:00 Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility Mbarek, Hamdi Steinberg, Stacy Nyholt, Dale Gordon, Scott Miller, Michael other, and 2016 https://eprints.qut.edu.au/222074/ unknown Cell Press doi:10.1016/j.ajhg.2016.03.008 Mbarek, Hamdi, Steinberg, Stacy, Nyholt, Dale, Gordon, Scott, Miller, Michael, & other, and (2016) Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility. American Journal of Human Genetics, 98(5), pp. 898-908. https://eprints.qut.edu.au/222074/ Faculty of Health; Institute of Health and Biomedical Innovation; School of Biomedical Sciences Consult author(s) regarding copyright matters This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au American Journal of Human Genetics Anxiety genetics Depression genetics DizygoticTwins genetics Fertility genetics Genome-Wide Association Study Contribution to Journal 2016 ftqueensland https://doi.org/10.1016/j.ajhg.2016.03.008 2024-01-01T23:33:07Z This article is free to read at the publisher's website 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 x 10(-9), and rs17293443 in SMAD3, p = 1.57 x 10(-8)) and replicated (p = 3 x 10(-3) and p = 1.44 x 10(-4), respectively). Based on approximately 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. Article in Journal/Newspaper Iceland Queensland University of Technology: QUT ePrints The American Journal of Human Genetics 98 5 898 908 |
institution |
Open Polar |
collection |
Queensland University of Technology: QUT ePrints |
op_collection_id |
ftqueensland |
language |
unknown |
topic |
Anxiety genetics Depression genetics DizygoticTwins genetics Fertility genetics Genome-Wide Association Study |
spellingShingle |
Anxiety genetics Depression genetics DizygoticTwins genetics Fertility genetics Genome-Wide Association Study Mbarek, Hamdi Steinberg, Stacy Nyholt, Dale Gordon, Scott Miller, Michael other, and Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility |
topic_facet |
Anxiety genetics Depression genetics DizygoticTwins genetics Fertility genetics Genome-Wide Association Study |
description |
This article is free to read at the publisher's website 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 x 10(-9), and rs17293443 in SMAD3, p = 1.57 x 10(-8)) and replicated (p = 3 x 10(-3) and p = 1.44 x 10(-4), respectively). Based on approximately 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. |
format |
Article in Journal/Newspaper |
author |
Mbarek, Hamdi Steinberg, Stacy Nyholt, Dale Gordon, Scott Miller, Michael other, and |
author_facet |
Mbarek, Hamdi Steinberg, Stacy Nyholt, Dale Gordon, Scott Miller, Michael other, and |
author_sort |
Mbarek, Hamdi |
title |
Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility |
title_short |
Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility |
title_full |
Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility |
title_fullStr |
Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility |
title_full_unstemmed |
Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility |
title_sort |
identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility |
publisher |
Cell Press |
publishDate |
2016 |
url |
https://eprints.qut.edu.au/222074/ |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
American Journal of Human Genetics |
op_relation |
doi:10.1016/j.ajhg.2016.03.008 Mbarek, Hamdi, Steinberg, Stacy, Nyholt, Dale, Gordon, Scott, Miller, Michael, & other, and (2016) Identification of common genetic variants influencing spontaneous dizygotic twinning and female fertility. American Journal of Human Genetics, 98(5), pp. 898-908. https://eprints.qut.edu.au/222074/ Faculty of Health; Institute of Health and Biomedical Innovation; School of Biomedical Sciences |
op_rights |
Consult author(s) regarding copyright matters This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au |
op_doi |
https://doi.org/10.1016/j.ajhg.2016.03.008 |
container_title |
The American Journal of Human Genetics |
container_volume |
98 |
container_issue |
5 |
container_start_page |
898 |
op_container_end_page |
908 |
_version_ |
1789333712436985856 |