Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

Iain Mathieson, Felix R. Day, Nicola Barban, Felix C Tropf, David M Brazel, eQTLGen Consortium, BIOS Consortium, 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, FinnGen Study, 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, Lifelines Cohort Study, 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
Nature human behaviour · 2023 · vol. 7(5) , pp. 790–801 · doi:10.1038/s41562-023-01528-6 · PMID:36864135
other OA: green public-domain-us
🔓 Open OA copy Full text JSON View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This genome-wide analysis of nearly 800,000 individuals identified 43 loci linked to reproductive success and highlighted the FADS locus as an example of ongoing natural selection influencing fertility traits.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-14 · read from full text ⓘ

This study used genome-wide data from 785,604 European-ancestry individuals to identify genetic loci associated with reproductive success, measured as number of children ever born (NEB) and childlessness, and to infer alleles under ongoing natural selection. The authors found 43 associated loci spanning multiple reproductive-biology pathways, including puberty timing, age at first birth, sex hormone regulation, and also reported that coding missense variants in ARHGAP27 were linked to higher NEB but shorter reproductive lifespan, indicating a trade-off related to reproductive ageing. They integrated association results with historical selection scans to highlight an allele in the FADS1/2 locus that has been under selection for thousands of years and persists today. The paper includes endometriosis among the reproductive processes covered by implicated loci, and relevance to endometriosis: it cites “endometriosis” as part of the reproductive-biology pathways spanned by the identified genetic associations, though the paper’s main focus is genome-wide identification of loci affecting reproductive success and selection.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

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.
Full text 2,951 characters · extracted from oa-html · click to expand
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. | Original language | English | |---|---| | Pages (from-to) | 790-801 | | Number of pages | 12 | | Journal | Nature Human Behaviour | | Volume | 7 | | Issue number | 5 | | Early online date | 2 Mar 2023 | | DOIs | | | Publication status | Published - May 2023 | Bibliographical note Funding Information:This research was conducted using the UK Biobank Resource under application no. 9905. This work was supported by the Medical Research Council (Unit Programme numbers MC_UU_12015/2 and MC_UU_00006/2); ERC grant nos 615603, 835079 and 865356; ESRC ES/N011856/1; the Leverhulme Trust; the Leverhulme Centre for Demographic Science; and LabEx Ecodec ANR grant no. ANR-11-LABX-0047. Full study-specific and individual acknowledgements can be found in the . The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the funders. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. This study received ethical approval from the Department of Sociology, University of Oxford 2014/01/01/R3, 28 January 2014 (SOCIOGENOME) and revised with extension SOC/R2/001/C1A/21/60 7 July 2022 (CHRONO), and relevant ethical approval was obtained at the local level for the contributing datasets. Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature Limited. Fingerprint Dive into the research topics of 'Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus'. Together they form a unique fingerprint.Cite this - APA - Author - BIBTEX - Harvard - Standard - RIS - Vancouver

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-html ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

MeSH descriptors

Fertility Fertility Fertility Fertility Fertility Fertility Fertility Fertility Fertility Fertility Fertility Fertility Fertility Fertility Fertility Reproduction Reproduction Reproduction Reproduction Reproduction

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. The paper's references may be in our DB but unresolved to ``paper_id`` (resolution happens at ingest when the cited DOI matches a row we already have). Run the cross-source citation reconcile pass to retry.

Source provenance

europepmc
last seen: 2026-06-22T06:15:23.361955+00:00
pubmed
last seen: 2026-06-22T06:14:40.508420+00:00
unpaywall
last seen: 2026-05-14T19:30:52.867331+00:00
License: public-domain-us · commercial use OK · attribution required
Courtesy of the U.S. National Library of Medicine