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; Peter Donnelly

doi:10.1038/ncomms8846

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 journal › Article › peer-review

Abstract / Description of output

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 language	English
Pages (from-to)	7846
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8846
Publication status	Published - 5 Aug 2015

Access to Document

10.1038/ncomms8846

Cite this

Martin, H. C., Christ, R., Hussin, J. G., O'Connell, J., Gordon, S., Mbarek, H., Hottenga, J.-J., McAloney, K., Willemsen, G., Gasparini, P., Pirastu, N., Montgomery, G. W., Navarro, P., Soranzo, N., Toniolo, D., Vitart, V., Wilson, J. F., Marchini, J., Boomsma, D. I., ... Donnelly, P. (2015). Multicohort analysis of the maternal age effect on recombination. Nature Communications, 6, 7846. https://doi.org/10.1038/ncomms8846

@article{5ebab839d0414d4a995bf3d69fc5cdc6,

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.",

author = "Martin, {Hilary C} and Ryan Christ and Hussin, {Julie G} and Jared O'Connell and Scott Gordon and Hamdi Mbarek and Jouke-Jan Hottenga and Kerrie McAloney and Gonnecke Willemsen and Paolo Gasparini and Nicola Pirastu and Montgomery, {Grant W} and Pau Navarro and Nicole Soranzo and Daniela Toniolo and Veronique Vitart and Wilson, {James F} and Jonathan Marchini and Boomsma, {Dorret I} and Martin, {Nicholas G} and Peter Donnelly",

year = "2015",

month = aug,

day = "5",

doi = "10.1038/ncomms8846",

language = "English",

volume = "6",

pages = "7846",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Martin, HC, Christ, R, Hussin, JG, O'Connell, J, Gordon, S, Mbarek, H, Hottenga, J-J, McAloney, K, Willemsen, G, Gasparini, P, Pirastu, N, Montgomery, GW, Navarro, P, Soranzo, N, Toniolo, D, Vitart, V , Wilson, JF, Marchini, J, Boomsma, DI, Martin, NG & Donnelly, P 2015, 'Multicohort analysis of the maternal age effect on recombination', Nature Communications, vol. 6, pp. 7846. https://doi.org/10.1038/ncomms8846

TY - JOUR

T1 - Multicohort analysis of the maternal age effect on recombination

AU - Martin, Hilary C

AU - Christ, Ryan

AU - Hussin, Julie G

AU - O'Connell, Jared

AU - Gordon, Scott

AU - Mbarek, Hamdi

AU - Hottenga, Jouke-Jan

AU - McAloney, Kerrie

AU - Willemsen, Gonnecke

AU - Gasparini, Paolo

AU - Pirastu, Nicola

AU - Montgomery, Grant W

AU - Navarro, Pau

AU - Soranzo, Nicole

AU - Toniolo, Daniela

AU - Vitart, Veronique

AU - Wilson, James F

AU - Marchini, Jonathan

AU - Boomsma, Dorret I

AU - Martin, Nicholas G

AU - Donnelly, Peter

PY - 2015/8/5

Y1 - 2015/8/5

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms8846

DO - 10.1038/ncomms8846

M3 - Article

C2 - 26242864

SN - 2041-1723

VL - 6

SP - 7846

JO - Nature Communications

JF - Nature Communications

ER -

Multicohort analysis of the maternal age effect on recombination

Abstract / Description of output

Access to Document

Fingerprint

Cite this