Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores.
Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores.
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DOI：
10.1186/s12916-021-02216-w
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发表时间：
2022-02-01
期刊：
影响因子：
9.3
通讯作者：
Järvelin MR
中科院分区：
文献类型：
--
作者：
Bond TA;Richmond RC;Karhunen V;Cuellar-Partida G;Borges MC;Zuber V;Couto Alves A;Mason D;Yang TC;Gunter MJ;Dehghan A;Tzoulaki I;Sebert S;Evans DM;Lewin AM;O'Reilly PF;Lawlor DA;Järvelin MR
母亲在怀孕前或怀孕期间的肥胖与后代在整个儿童期的肥胖有关，但这在多大程度上是由于宫内或围受孕机制的原因尚不清楚。在这里，我们使用孟德尔随机化（MR）与多基因风险评分（PRS），以调查母亲孕前/早孕体重指数（BMI）和后代肥胖从出生到青春期之间的关联是否是因果关系。我们进行了混杂因素调整的多变量（MV）回归和MR使用来自两个英国队列的母子对：雅芳父母和子女纵向研究（ALSPAC）和出生在布拉德福德（BiB）。在ALSPAC和BiB中，结局为出生体重（BW; N = 9339）和1岁和4岁时的BMI（N = 8659至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线吸收测定法（DXA）测定了10-18岁时的脂肪质量指数（FMI）（N = 2659至3855）。我们比较了几种PRS的MR结果，这些PRS是根据29至80，939个单核苷酸多态性（SNP）的母体非传播等位基因计算的。MV和MR一致显示母体BMI和BW之间呈正相关，支持中度因果效应。对于大多数老年人的肥胖，尽管MV估计值表明了很强的正相关性，但MR估计值不支持因果关系。对于具有很少SNP的PRS，MR估计值与空值在统计学上一致，但具有宽置信区间，因此通常也与MV估计值在统计学上一致。相比之下，最大的PRS产生的MR估计值的置信区间较窄，提供了强有力的证据表明，对青少年肥胖的真正因果影响小于MV估计值（15年BMI的P差异= 0.001）。这表明MV估计值受残余混杂影响，因此不能准确指示因果效应量。我们的研究结果表明，母亲怀孕前/怀孕早期BMI较高并不是下一代肥胖率较高的关键驱动因素。因此，他们支持针对全体人口的干预措施，以减少超重和肥胖，而不是特别关注育龄妇女。在线版本包含补充材料，可通过10.1186/s12916-021-02216-w获得。
Greater 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. We 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). MV 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. Our 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. The online version contains supplementary material available at 10.1186/s12916-021-02216-w.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
怀孕前体重指数与后代代谢概况的关联：3个欧洲前瞻性出生队列的分析。
影响因子：
15.8
作者：
Santos Ferreira DL;Williams DM;Kangas AJ;Soininen P;Ala-Korpela M;Smith GD;Jarvelin MR;Lawlor DA
通讯作者：
Lawlor DA
DOI：
10.1093/bioinformatics/btu848
发表时间：
2015-05-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Euesden J;Lewis CM;O'Reilly PF
通讯作者：
O'Reilly PF
影响因子：
4.5
作者：
Evans DM;Brion MJ;Paternoster L;Kemp JP;McMahon G;Munafò M;Whitfield JB;Medland SE;Montgomery GW;GIANT Consortium;CRP Consortium;TAG Consortium;Timpson NJ;St Pourcain B;Lawlor DA;Martin NG;Dehghan A;Hirschhorn J;Smith GD
通讯作者：
Smith GD