title: Multicohort analysis of the maternal age effect on recombination.
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.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX17BN, UK.
authors.forename: Hilary C
authors.initials: HC
authors.lastname: Martin
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX17BN, UK.
authors.forename: Ryan
authors.initials: R
authors.lastname: Christ
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX17BN, UK.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Hussin
authors.affiliation: Illumina, Inc., Chesterford Research Park, Little Chesterford CB10 1XL, UK.
authors.forename: Jared
authors.initials: J
authors.lastname: O'Connell
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Department for Biological Psychiatry, Vrije Universiteit, Amsterdam 1081, The Netherlands.
authors.forename: Hamdi
authors.initials: H
authors.lastname: Mbarek
authors.affiliation: Department for Biological Psychiatry, Vrije Universiteit, Amsterdam 1081, The Netherlands.
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
authors.forename: Kerrie
authors.initials: K
authors.lastname: McAloney
authors.affiliation: Department for Biological Psychiatry, Vrije Universiteit, Amsterdam 1081, The Netherlands.
authors.forename: Gonnecke
authors.initials: G
authors.lastname: Willemsen
authors.affiliation: Institute for Maternal and Child Health-IRCCS Burlo Garofolo, University of Trieste, Trieste 34137, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.affiliation: Institute for Maternal and Child Health-IRCCS Burlo Garofolo, University of Trieste, Trieste 34137, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pirastu
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Pau
authors.initials: P
authors.lastname: Navarro
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton CB10 1HH, UK.
authors.forename: Nicole
authors.identifier: http://orcid.org/0000-0003-1095-3852
authors.initials: N
authors.lastname: Soranzo
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan 20132, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Toniolo
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.|Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH16 4TJ, UK.
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX17BN, UK.|Department of Statistics, University of Oxford, Oxford OX1 3TG, UK.
authors.forename: Jonathan
authors.identifier: http://orcid.org/0000-0003-0610-8322
authors.initials: J
authors.lastname: Marchini
authors.affiliation: Department for Biological Psychiatry, Vrije Universiteit, Amsterdam 1081, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX17BN, UK.|Department of Statistics, University of Oxford, Oxford OX1 3TG, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Donnelly
mesh_terms: D000782:Aneuploidy; D001499:Bayes Theorem; D015331:Cohort Studies; D003434:Crossing Over, Genetic; D006801:Humans; D016014:Linear Models; D008423:Maternal Age; D008957:Models, Genetic; D011995:Recombination, Genetic