親のBMIと子供の肥満度との関連性:トリオデータを用いた遺伝学的に情報に基づいた分析(The association between parental BMI and offspring adiposity: A genetically informed analysis of trios)

2025-08-06 ユニバーシティ・カレッジ・ロンドン(UCL)

<関連情報>

• https://www.ucl.ac.uk/news/2025/aug/mothers-genes-may-shape-childrens-weight-even-without-being-passed-down
• https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1011775

親のBMIと子供の肥満度との関連性:トリオデータを用いた遺伝学的に情報に基づいた分析 The association between parental BMI and offspring adiposity: A genetically informed analysis of trios

Liam Wright ,Gemma Shireby,Tim T. Morris,Neil M. Davies,David Bann
PLOS Genetics  Published: August 5, 2025
DOI:https://doi.org/10.1371/journal.pgen.1011775

Abstract

Background

Children with obesity are more likely to have parents with obesity than those without. Several environmental explanations have been proposed for this correlation, including foetal programming and parenting practices. However, body mass index (BMI) is a heritable trait; child-parent correlations may reflect direct inheritance of adiposity-related genes. There is some evidence that mothers’ 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 fathers’ BMI as well as offsprings’ diet as a mediating factor.

Methods

We used Mendelian Randomization (MR) with genetic trio (mother-father-offspring) data from 2,630 families in the Millennium Cohort Study, a UK birth cohort study of individuals born in 2000/02, 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 conditioning upon offspring PGI. This allowed us to separate direct and indirect (“genetic nurture”) genetic effects. We compared these results with associations obtained using standard multivariable regression techniques using phenotypic BMI data only.

Results

Mothers’ and fathers’ 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. In contrast, mother’s BMI was consistent in MR analysis with phenotypic associations. Maternal indirect genetic effects were between 25–50% the size of direct genetic effects. There was limited and inconsistent evidence of associations with offspring diet and some evidence that mothers’, but not fathers’, BMI was related to birthweight in both MR and multivariable regression models.

Conclusions

Results suggest 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 of father’s and offspring adiposity that do not account for direct genetic inheritance may yield biased estimates of paternal influence. Larger studies are required to confirm these findings.

Author summary

Children with obesity are more likely to have parents with obesity, too. This may be explained by environmental factors, such as prenatal conditions in utero or postnatal parental behaviours (e.g., the foods parents provide). If this is the case, interventions to reduce parental body mass index (BMI) could have intergenerational effects. However, the correlation between parent-child adiposity may reflect children inheriting obesity-related genes from their parents. To explore this, we used genetic data from over 2,500 trios (mother-father-offspring sets) to assess whether parental obesity-related genes are associated with offspring adiposity and diet after accounting for direct genetic inheritance. We compared this to analyses that do not account for genetic inheritance. We found that, though mothers’ and fathers’ BMI were consistently correlated with children’s BMI, after accounting for direct genetic inheritance, this only remained true for mothers during the child’s adolescence. Associations of parents’ BMI and children’s diet were less consistent. Our results suggest that associations between fathers’ and children’s adiposity that do not account for direct genetic inheritance yield biased estimates of paternal influence.