Abstract
BackgroundMaternal 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/ResultsIn 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.ConclusionsMaternal genetic variation may account in part for associations of GWG with offspring BMI and WC in young adults.
Highlights
The enduring consequences of maternal perinatal obesity are being recognized
Maternal genetic variation may account in part for associations of gestational weight gain (GWG) with offspring body mass index (BMI) and Waist circumference (WC) in young adults
Limited evidence suggests that genes that are reliably and strongly associated with obesity may not be important in influencing gestational weight gain [9]; maternal genetic variation may act differently in associations of offspring cardiometabolic risk (CMR) with maternal pre-pregnancy BMI or GWG
Summary
The enduring consequences of maternal perinatal obesity (pre-pregnancy obesity and excess gestational weight gain) are being recognized. A recent analysis by our group demonstrated associations of maternal pre-pregnancy body-mass index (BMI) and gestational weight gain (GWG) with adulthood obesity-related risk factors for metabolic and cardiovascular diseases in the offspring [1]. These findings are especially concerning given current epidemic rates of pre-pregnancy obesity and excess GWG [2,3]. Previous analyses have provided limited evidence for an effect of maternal genetic variation on the association of measures of maternal perinatal obesity with offspring obesity at birth [6], in childhood [7] and in young adulthood [8] using study designs such as linear mixed models (that use clustering or other statistical techniques to account for shared maternal characteristics, including maternal genetic variation). The extent to which maternal genetic variation accounts for these associations is unknown
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