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Multicohort analysis of the maternal age effect on recombination

Author

Listed:
  • Hilary C. Martin

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Ryan Christ

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Julie G. Hussin

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Jared O’Connell

    (Illumina, Inc., Chesterford Research Park)

  • Scott Gordon

    (QIMR Berghofer Medical Research Institute)

  • Hamdi Mbarek

    (Vrije Universiteit)

  • Jouke-Jan Hottenga

    (Vrije Universiteit)

  • Kerrie McAloney

    (QIMR Berghofer Medical Research Institute)

  • Gonnecke Willemsen

    (Vrije Universiteit)

  • Paolo Gasparini

    (Institute for Maternal and Child Health—IRCCS Burlo Garofolo, University of Trieste)

  • Nicola Pirastu

    (Institute for Maternal and Child Health—IRCCS Burlo Garofolo, University of Trieste)

  • Grant W. Montgomery

    (QIMR Berghofer Medical Research Institute)

  • Pau Navarro

    (MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Nicole Soranzo

    (Wellcome Trust Sanger Institute)

  • Daniela Toniolo

    (San Raffaele Scientific Institute)

  • Veronique Vitart

    (MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • James F. Wilson

    (MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh
    Institute for Population Health Sciences and Informatics, University of Edinburgh)

  • Jonathan Marchini

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    University of Oxford)

  • Dorret I. Boomsma

    (Vrije Universiteit)

  • Nicholas G. Martin

    (QIMR Berghofer Medical Research Institute)

  • Peter Donnelly

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    University of Oxford)

Abstract

Several studies have reported that the number of crossovers increases with maternal age in humans, but others have found the opposite. Resolving the true effect has implications for understanding the maternal age effect on aneuploidies. Here, we revisit this question in the largest sample to date using single nucleotide polymorphism (SNP)-chip data, comprising over 6,000 meioses from nine cohorts. We develop and fit a hierarchical model to allow for differences between cohorts and between mothers. We estimate that over 10 years, the expected number of maternal crossovers increases by 2.1% (95% credible interval (0.98%, 3.3%)). Our results are not consistent with the larger positive and negative effects previously reported in smaller cohorts. We see heterogeneity between cohorts that is likely due to chance effects in smaller samples, or possibly to confounders, emphasizing that care should be taken when interpreting results from any specific cohort about the effect of maternal age on recombination.

Suggested Citation

  • Hilary C. Martin & Ryan Christ & Julie G. Hussin & Jared O’Connell & Scott Gordon & Hamdi Mbarek & Jouke-Jan Hottenga & Kerrie McAloney & Gonnecke Willemsen & Paolo Gasparini & Nicola Pirastu & Grant , 2015. "Multicohort analysis of the maternal age effect on recombination," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8846
    DOI: 10.1038/ncomms8846
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