Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomization using polygenic risk scores
Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomization using polygenic risk scores
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探索母亲妊娠肥胖对后代肥胖的因果影响：使用多基因风险评分的孟德尔随机化
DOI：
10.1101/2021.04.01.21251414
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Bond T
中科院分区：
文献类型：
--
作者：
Bond T
背景：孕期或孕前孕妇肥胖程度越高，其后代在整个儿童期肥胖程度越高，但这在多大程度上是由于宫内或围孕期的因果机制尚不清楚。在这里，我们使用孟德尔随机化（MR）和多基因风险评分（PRS）来研究母亲孕前/早孕体重指数（BMI）与后代从出生到青春期肥胖之间是否存在因果关系。方法我们采用混杂因素调整的多变量（MV）回归和MR方法，使用来自两个英国队列的母亲-后代对：雅芳父母和儿童纵向研究（ALSPAC）和出生在布拉德福德（BiB）。在ALSPAC和BiB中，结果是出生体重（BW；N= 9339）和1岁和4岁时BMI （N= 8659 ~ 7575）。仅在ALSPAC中，我们调查了10岁和15岁时的BMI (N= 4476至4112)，双能x线吸收仪（DXA）测定了10 - 18岁时的脂肪质量指数（FMI） （N= 2659至3855）。我们比较了几个PRS的MR结果，这些PRS是从29到80,939个单核苷酸多态性（snp）的母体非遗传等位基因中计算出来的。结果smv和MR一致显示母亲BMI与体重呈正相关，支持中等因果关系。对于大多数老年人的肥胖，尽管MV估计显示出强烈的正相关，但MR估计不支持因果关系。对于snp较少的PRS， MR估计值在统计上与零值一致，但具有较宽的置信区间，因此通常也与MV估计值在统计上一致。相比之下，最大的PRS产生的MR估计值具有更窄的置信区间，这提供了强有力的证据，表明青少年肥胖的真正因果效应小于MV估计值（15年BMI的Pdifference= 0.001）。这表明MV估计受到残留混淆的影响，因此不能提供因果效应大小的准确指示。结论母体孕前/孕早期BMI增高不是下一代肥胖增高的关键驱动因素。因此，他们支持针对全体人口减少超重和肥胖的干预措施，而不是专门针对育龄妇女。
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 randomisation (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 results suggest that higher maternal pre-/early-pregnancy BMI is not a key driver of higher adiposity in the next generation. Thus, they support interventions that target the whole population for reducing overweight and obesity, rather than a specific focus on women of reproductive age.
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影响因子：
7.7
作者：
Wright, John;Small, Neil;West, Jane
通讯作者：
West, Jane
父母孕前BMI对后代21岁时BMI和腰围的影响
影响因子：
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影响因子：
5.9
作者：
C. Patel;E. Karasouli;E. Shuttlewood;C. Meyer
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