| Title: | Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus |
| Journal: | Nature Human Behaviour |
| Published: | 2 Mar 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36864135/ |
| DOI: | https://doi.org/10.1038/s41562-023-01528-6 |
| URL: | https://pure.rug.nl/ws/files/701079506/s41562-023-01528-6.pdf |
Publication 11163
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success.</p>
121 Authors
- Iain Mathieson
- Felix R. Day
- Nicola Barban
- Felix C. Tropf
- David M. Brazel
- Ahmad Vaez
- Natalie van Zuydam
- Bárbara D. Bitarello
- Eugene J. Gardner
- Evelina T. Akimova
- Ajuna Azad
- Sven Bergmann
- Lawrence F. Bielak
- Dorret I. Boomsma
- Kristina Bosak
- Marco Brumat
- Julie E. Buring
- David Cesarini
- Daniel I. Chasman
- Jorge E. Chavarro
- Massimiliano Cocca
- Maria Pina Concas
- George Davey Smith
- Gail Davies
- Ian J. Deary
- Tõnu Esko
- Jessica D. Faul
- Oscar Franco
- Andrea Ganna
- Audrey J. Gaskins
- Andrea Gelemanovic
- Eco J. C. de Geus
- Christian Gieger
- Giorgia Girotto
- Bamini Gopinath
- Hans Jörgen Grabe
- Erica P. Gunderson
- Caroline Hayward
- Chunyan He
- Diana van Heemst
- W. David Hill
- Eva R. Hoffmann
- Georg Homuth
- Jouke Jan Hottenga
- Hongyang Huang
- Elina Hyppӧnen
- M. Arfan Ikram
- Rick Jansen
- Magnus Johannesson
- Zoha Kamali
- Sharon L. R. Kardia
- Maryam Kavousi
- Annette Kifley
- Tuomo Kiiskinen
- Peter Kraft
- Brigitte Kühnel
- Claudia Langenberg
- Gerald Liew
- Penelope A. Lind
- Jian'an Luan
- Reedik Mägi
- Patrik K. E. Magnusson
- Anubha Mahajan
- Nicholas G. Martin
- Hamdi Mbarek
- Mark I. McCarthy
- George McMahon
- Sarah E. Medland
- Thomas Meitinger
- Andres Metspalu
- Evelin Mihailov
- Lili Milani
- Stacey A. Missmer
- Paul Mitchell
- Stine Møllegaard
- Dennis O. Mook-Kanamori
- Anna Morgan
- Peter J. van der Most
- Renée de Mutsert
- Matthias Nauck
- Ilja M. Nolte
- Raymond Noordam
- Brenda W. J. H. Penninx
- Annette Peters
- Patricia A. Peyser
- Ozren Polašek
- Chris Power
- Ajka Pribisalic
- Paul Redmond
- Janet W. Rich-Edwards
- Paul M. Ridker
- Cornelius A. Rietveld
- Susan M. Ring
- Lynda M. Rose
- Rico Rueedi
- Vallari Shukla
- Jennifer A. Smith
- Stasa Stankovic
- Kári Stefánsson
- Doris Stöckl
- Konstantin Strauch
- Morris A. Swertz
- Alexander Teumer
- Gudmar Thorleifsson
- Unnur Thorsteinsdottir
- A. Roy Thurik
- Nicholas J. Timpson
- Constance Turman
- André G. Uitterlinden
- Melanie Waldenberger
- Nicholas J. Wareham
- David R. Weir
- Gonneke Willemsen
- Jing Hau Zhao
- Wei Zhao
- Yajie Zhao
- Harold Snieder
- Marcel den Hoed
- Ken K. Ong
- Melinda C. Mills
- John R. B. Perry
1 Application
| Application ID | Title |
|---|---|
| 9905 | Using genetics to elucidate the relationship between socioeconomic/behavioural traits and disease |
Enabling scientific discoveries that improve human health