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@article{Bond:2022:10.1186/s12916-021-02216-w,
author = {Bond, T and Richmond, R and Karhunen, V and Cuellar-Partida, G and Borges, MC and Zuber, V and Couto, Alves A and Mason, D and Yang, T and Gunter, M and Dehghan, A and Tzoulaki, I and Sebert, S and Evans, D and Lewin, A and O'Reilly, P and Lawlor, D and Jarvelin, M-R},
doi = {10.1186/s12916-021-02216-w},
journal = {BMC Medicine},
title = {Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomization using polygenic risk scores},
url = {http://dx.doi.org/10.1186/s12916-021-02216-w},
volume = {20},
year = {2022}
}

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TY  - JOUR
AB  - BackgroundGreater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here we use Mendelian Randomization (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal.MethodsWe undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB the outcomes were birthweight (BW; N = 9339) and BMI at age 1 and 4 years (N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years (N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10–18 years (N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs).ResultsMV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates (Pdifference = 0.001 for 15 year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size.ConclusionsOur re
AU  - Bond,T
AU  - Richmond,R
AU  - Karhunen,V
AU  - Cuellar-Partida,G
AU  - Borges,MC
AU  - Zuber,V
AU  - Couto,Alves A
AU  - Mason,D
AU  - Yang,T
AU  - Gunter,M
AU  - Dehghan,A
AU  - Tzoulaki,I
AU  - Sebert,S
AU  - Evans,D
AU  - Lewin,A
AU  - O'Reilly,P
AU  - Lawlor,D
AU  - Jarvelin,M-R
DO  - 10.1186/s12916-021-02216-w
PY  - 2022///
SN  - 1741-7015
TI  - Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomization using polygenic risk scores
T2  - BMC Medicine
UR  - http://dx.doi.org/10.1186/s12916-021-02216-w
UR  - https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02216-w
UR  - http://hdl.handle.net/10044/1/94173
VL  - 20
ER  -

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