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

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Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus. / Mathieson, Iain; Day, Felix R.; Barban, Nicola; Tropf, Felix C.; Brazel, David M.; van Heemst, Diana; Vaez, Ahmad; van Zuydam, Natalie; Bitarello, Bárbara D.; Gardner, Eugene J.; Akimova, Evelina T.; Azad, Ajuna; Bergmann, Sven; Bielak, Lawrence F.; Boomsma, Dorret I.; Bosak, Kristina; Brumat, Marco; Buring, Julie E.; Cesarini, David; Chasman, Daniel I.; Chavarro, Jorge E.; Cocca, Massimiliano; Concas, Maria Pina; Davey Smith, George; Davies, Gail; Deary, Ian J.; Esko, Tõnu; Faul, Jessica D.; Franco, Oscar; Ganna, Andrea; Gaskins, Audrey J.; Gelemanovic, Andrea; de Geus, Eco J.C.; Gieger, Christian; Girotto, Giorgia; Gopinath, Bamini; Grabe, Hans Jörgen; Gunderson, Erica P.; Hayward, Caroline; He, Chunyan; van Heemst, Diana; Hill, W. David; Hoffmann, Eva R.; Homuth, Georg; Hottenga, Jouke Jan; Huang, Hongyang; Hyppӧnen, Elina; Ikram, M. Arfan; Møllegaard, Stine; Shukla, Vallari; eQTLGen Consortium; BIOS Consortium; FinnGen Study; LifeLines Cohort Study.

I: Nature Human Behaviour, Bind 7, 790–801, 2023.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Mathieson, I, Day, FR, Barban, N, Tropf, FC, Brazel, DM, van Heemst, D, Vaez, A, van Zuydam, N, Bitarello, BD, Gardner, EJ, Akimova, ET, Azad, A, Bergmann, S, Bielak, LF, Boomsma, DI, Bosak, K, Brumat, M, Buring, JE, Cesarini, D, Chasman, DI, Chavarro, JE, Cocca, M, Concas, MP, Davey Smith, G, Davies, G, Deary, IJ, Esko, T, Faul, JD, Franco, O, Ganna, A, Gaskins, AJ, Gelemanovic, A, de Geus, EJC, Gieger, C, Girotto, G, Gopinath, B, Grabe, HJ, Gunderson, EP, Hayward, C, He, C, van Heemst, D, Hill, WD, Hoffmann, ER, Homuth, G, Hottenga, JJ, Huang, H, Hyppӧnen, E, Ikram, MA, Møllegaard, S, Shukla, V, eQTLGen Consortium, BIOS Consortium, FinnGen Study & LifeLines Cohort Study 2023, 'Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus', Nature Human Behaviour, bind 7, 790–801. https://doi.org/10.1038/s41562-023-01528-6

APA

Mathieson, I., Day, F. R., Barban, N., Tropf, F. C., Brazel, D. M., van Heemst, D., Vaez, A., van Zuydam, N., Bitarello, B. D., Gardner, E. J., Akimova, E. T., Azad, A., Bergmann, S., Bielak, L. F., Boomsma, D. I., Bosak, K., Brumat, M., Buring, J. E., Cesarini, D., ... LifeLines Cohort Study (2023). Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus. Nature Human Behaviour, 7, [790–801]. https://doi.org/10.1038/s41562-023-01528-6

Vancouver

Mathieson I, Day FR, Barban N, Tropf FC, Brazel DM, van Heemst D o.a. Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus. Nature Human Behaviour. 2023;7. 790–801. https://doi.org/10.1038/s41562-023-01528-6

Author

Mathieson, Iain ; Day, Felix R. ; Barban, Nicola ; Tropf, Felix C. ; Brazel, David M. ; van Heemst, Diana ; Vaez, Ahmad ; van Zuydam, Natalie ; Bitarello, Bárbara D. ; Gardner, Eugene J. ; Akimova, Evelina T. ; Azad, Ajuna ; Bergmann, Sven ; Bielak, Lawrence F. ; Boomsma, Dorret I. ; Bosak, Kristina ; Brumat, Marco ; Buring, Julie E. ; Cesarini, David ; Chasman, Daniel I. ; Chavarro, Jorge E. ; Cocca, Massimiliano ; Concas, Maria Pina ; Davey Smith, George ; Davies, Gail ; Deary, Ian J. ; Esko, Tõnu ; Faul, Jessica D. ; Franco, Oscar ; Ganna, Andrea ; Gaskins, Audrey J. ; Gelemanovic, Andrea ; de Geus, Eco J.C. ; Gieger, Christian ; Girotto, Giorgia ; Gopinath, Bamini ; Grabe, Hans Jörgen ; Gunderson, Erica P. ; Hayward, Caroline ; He, Chunyan ; van Heemst, Diana ; Hill, W. David ; Hoffmann, Eva R. ; Homuth, Georg ; Hottenga, Jouke Jan ; Huang, Hongyang ; Hyppӧnen, Elina ; Ikram, M. Arfan ; Møllegaard, Stine ; Shukla, Vallari ; eQTLGen Consortium ; BIOS Consortium ; FinnGen Study ; LifeLines Cohort Study. / Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus. I: Nature Human Behaviour. 2023 ; Bind 7.

Bibtex

@article{d4a9e70928324e7d95f31fb8ba83e678,
title = "Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus",
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.",
author = "Iain Mathieson and Day, {Felix R.} and Nicola Barban and Tropf, {Felix C.} and Brazel, {David M.} and {van Heemst}, Diana and Ahmad Vaez and {van Zuydam}, Natalie and Bitarello, {B{\'a}rbara D.} and Gardner, {Eugene J.} and Akimova, {Evelina T.} and Ajuna Azad and Sven Bergmann and Bielak, {Lawrence F.} and Boomsma, {Dorret I.} and Kristina Bosak and Marco Brumat and Buring, {Julie E.} and David Cesarini and Chasman, {Daniel I.} and Chavarro, {Jorge E.} and Massimiliano Cocca and Concas, {Maria Pina} and {Davey Smith}, George and Gail Davies and Deary, {Ian J.} and T{\~o}nu Esko and Faul, {Jessica D.} and Oscar Franco and Andrea Ganna and Gaskins, {Audrey J.} and Andrea Gelemanovic and {de Geus}, {Eco J.C.} and Christian Gieger and Giorgia Girotto and Bamini Gopinath and Grabe, {Hans J{\"o}rgen} and Gunderson, {Erica P.} and Caroline Hayward and Chunyan He and {van Heemst}, Diana and Hill, {W. David} and Hoffmann, {Eva R.} and Georg Homuth and Hottenga, {Jouke Jan} and Hongyang Huang and Elina Hyppӧnen and Ikram, {M. Arfan} and Stine M{\o}llegaard and Vallari Shukla and {eQTLGen Consortium} and {BIOS Consortium} and {FinnGen Study} and {LifeLines Cohort Study}",
note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2023",
doi = "10.1038/s41562-023-01528-6",
language = "English",
volume = "7",
journal = "Nature Human Behaviour",
issn = "2397-3374",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

AU - Mathieson, Iain

AU - Day, Felix R.

AU - Barban, Nicola

AU - Tropf, Felix C.

AU - Brazel, David M.

AU - van Heemst, Diana

AU - Vaez, Ahmad

AU - van Zuydam, Natalie

AU - Bitarello, Bárbara D.

AU - Gardner, Eugene J.

AU - Akimova, Evelina T.

AU - Azad, Ajuna

AU - Bergmann, Sven

AU - Bielak, Lawrence F.

AU - Boomsma, Dorret I.

AU - Bosak, Kristina

AU - Brumat, Marco

AU - Buring, Julie E.

AU - Cesarini, David

AU - Chasman, Daniel I.

AU - Chavarro, Jorge E.

AU - Cocca, Massimiliano

AU - Concas, Maria Pina

AU - Davey Smith, George

AU - Davies, Gail

AU - Deary, Ian J.

AU - Esko, Tõnu

AU - Faul, Jessica D.

AU - Franco, Oscar

AU - Ganna, Andrea

AU - Gaskins, Audrey J.

AU - Gelemanovic, Andrea

AU - de Geus, Eco J.C.

AU - Gieger, Christian

AU - Girotto, Giorgia

AU - Gopinath, Bamini

AU - Grabe, Hans Jörgen

AU - Gunderson, Erica P.

AU - Hayward, Caroline

AU - He, Chunyan

AU - van Heemst, Diana

AU - Hill, W. David

AU - Hoffmann, Eva R.

AU - Homuth, Georg

AU - Hottenga, Jouke Jan

AU - Huang, Hongyang

AU - Hyppӧnen, Elina

AU - Ikram, M. Arfan

AU - Møllegaard, Stine

AU - Shukla, Vallari

AU - eQTLGen Consortium

AU - BIOS Consortium

AU - FinnGen Study

AU - LifeLines Cohort Study

N1 - Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1038/s41562-023-01528-6

DO - 10.1038/s41562-023-01528-6

M3 - Journal article

C2 - 36864135

AN - SCOPUS:85149255018

VL - 7

JO - Nature Human Behaviour

JF - Nature Human Behaviour

SN - 2397-3374

M1 - 790–801

ER -

ID: 340110059