Wander Pandora L, Hochner Hagit, Sitlani Colleen M, Enquobahrie Daniel A, Lumley Thomas, Lawrence Gabriela M, Burger Ayala, Savitsky Bella, Manor Orly, Meiner Vardiella, Hesselson Stephanie, Kwok Pui Y, Siscovick David S, Friedlander Yechiel
Department of Epidemiology, University of Washington, Seattle, Washington, United States of America; Department of Medicine, University of Washington, Seattle, Washington, United States of America.
Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
PLoS One. 2014 Mar 26;9(3):e91835. doi: 10.1371/journal.pone.0091835. eCollection 2014.
Maternal pre-pregnancy body-mass index (ppBMI) and gestational weight gain (GWG) are associated with cardiometabolic risk (CMR) traits in the offspring. The extent to which maternal genetic variation accounts for these associations is unknown.
METHODS/RESULTS: In 1249 mother-offspring pairs recruited from the Jerusalem Perinatal Study, we used archival data to characterize ppBMI and GWG and follow-up data from offspring to assess CMR, including body mass index (BMI), waist circumference, glucose, insulin, blood pressure, and lipid levels, at an average age of 32. Maternal genetic risk scores (GRS) were created using a subset of SNPs most predictive of ppBMI, GWG, and each CMR trait, selected among 1384 single-nucleotide polymorphisms (SNPs) characterizing variation in 170 candidate genes potentially related to fetal development and/or metabolic risk. We fit linear regression models to examine the associations of ppBMI and GWG with CMR traits with and without adjustment for GRS. Compared to unadjusted models, the coefficient for the association of a one-standard-deviation (SD) difference in GWG and offspring BMI decreased by 41% (95%CI -81%, -11%) from 0.847 to 0.503 and the coefficient for a 1SD difference in GWG and WC decreased by 63% (95%CI -318%, -11%) from 1.196 to 0.443. For other traits, there were no statistically significant changes in the coefficients for GWG with adjustment for GRS. None of the associations of ppBMI with CMR traits were significantly altered by adjustment for GRS.
Maternal genetic variation may account in part for associations of GWG with offspring BMI and WC in young adults.
母亲孕前体重指数（ppBMI）和孕期体重增加（GWG）与后代的心脏代谢风险（CMR）特征相关。母亲的基因变异在多大程度上导致了这些关联尚不清楚。
方法/结果：在从耶路撒冷围产期研究中招募的1249对母婴中，我们使用存档数据来描述ppBMI和GWG，并利用后代的随访数据来评估CMR，包括平均年龄为32岁时的体重指数（BMI）、腰围、血糖、胰岛素、血压和血脂水平。母亲基因风险评分（GRS）是使用最能预测ppBMI、GWG和每种CMR特征的单核苷酸多态性（SNP）子集创建的，这些SNP是从1384个单核苷酸多态性（SNP）中挑选出来的，这些SNP表征了170个可能与胎儿发育和/或代谢风险相关的候选基因的变异。我们拟合线性回归模型，以检验在调整和未调整GRS的情况下，ppBMI和GWG与CMR特征之间的关联。与未调整模型相比，GWG每增加一个标准差（SD）与后代BMI之间关联的系数从0.847降至0.503，下降了41%（95%CI -81%，-11%）；GWG每增加1SD与腰围之间关联的系数从1.196降至0.443，下降了63%（95%CI -318%，-11%）。对于其他特征，调整GRS后GWG的系数没有统计学上的显著变化。调整GRS后，ppBMI与CMR特征之间的关联均未发生显著改变。
母亲的基因变异可能部分解释了GWG与年轻成年人后代BMI和腰围之间的关联。
