The Association Between Parental BMI and Offspring Adiposity: A Genetically Informed Analysis of Trios

Abstract

AbstractBackgroundChildren with obesity are more likely to have parents with obesity, too. Several environmental explanations have been proposed for this correlation, including foetal programming, and parenting practices. However, body mass index (BMI) is a highly heritable trait; child-parent correlations may reflect direct inheritance of adiposity-related genes. There is some evidence that mother’s BMI associates with offspring BMI net of direct genetic inheritance, consistent with both intrauterine and parenting effects, but this requires replication. Here we also investigate the role of father’s BMI and diet as a mediating parenting factor.MethodsWe used Mendelian Randomization (MR) with genetic trio (mother-father-offspring) data from 2,621 families in the Millennium Cohort Study, a UK birth cohort study of individuals born in 2001/02, to examine the association between parental BMI (kg/m2) and offspring birthweight and BMI and diet measured at six-time points between ages 3y and 17y. Paternal and maternal BMI were instrumented with polygenic indices (PGI) for BMI also conditioning upon offspring PGI. This allowed us to separate direct and indirect (“genetic nurture”) genetic effects. We compared these results with associations obtained using multivariable regression techniques using phenotypic BMI data only, the standard research approach.ResultsMother’s and father’s BMI were positively associated with offspring BMI to similar degrees. However, in MR analysis, associations between father’s BMI and offspring BMI were close to the null, suggesting phenotypic associations reflect the direct transmission of genetic traits. In contrast, mother’s BMI was consistent in MR analysis with phenotypic associations. Maternal indirect genetic effects were between 20-50% the size of direct genetic effects. There was inconsistent evidence of associations with offspring diet. Mother’s, but not father’s, BMI was related to birthweight in both MR and multivariable regression models.ConclusionResults suggest that maternal BMI may be particularly important for offspring BMI: associations may arise due to both direct transmission of genetic effects and indirect (genetic nurture) effects. Associations between father’s and offspring adiposity that do not account for direct genetic inheritance may yield severely biased estimates of paternal influence.