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 MartinPeter Donnelly

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)7846
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 5 Aug 2015

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