Multicohort analysis of the maternal age effect on recombination

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 W. Montgomery, Pau Navarro, Nicole Soranzo, Daniela Toniolo, Veronique Vitart, James F. Wilson, Jonathan Marchini, Dorret I. Boomsma, Nicholas G. Martin and Peter Donnelly ()
Additional contact information
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
Jonathan Marchini: Wellcome Trust Centre for Human Genetics, 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

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8846

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