Genetic nurture and direct genetic transmission effects on body mass index across age
- 1Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Abstract
Obesity is a growing public health challenge, with body mass index (BMI) influenced by both genetic and environmental factors. While the role of direct genetic transmission is well established, evidence for genetic nurture effects, in which parental genotypes impact offspring through the environment, has remained mixed. This study investigates direct genetic transmission and genetic nurture effects on BMI across ages, using parent-offspring trios and pairs from the Dutch Lifelines cohort study (N = 18,897 offspring, aged 8-67 years). We leveraged the latest multi-ancestry BMI polygenic score (PGS) to construct transmitted (PGS-T) and non-transmitted (PGS-NT) polygenic scores, where PGS-NT consists of parental alleles not passed on to offspring and serves as a proxy for genetic nurture. Linear mixed models showed a large effect of PGS-T on offspring BMI ({beta} = 0.416, p < 0.001), corresponding to a 1.85 kg/m{superscript 2} increase per SD increase in PGS-T. PGS-NT had a small but significant effect ({beta} = 0.026, p = 0.013), consistent with a genetic nurture effect accounting for approximately 6.6% of the effect of direct transmission. Parent-of-origin analyses showed that maternal PGS-NT effects were larger than paternal effects. PGS-T interactions with age indicated that direct transmission effects increased in childhood and stabilized in adulthood, while PGS-NT effects remained stable across age. Our findings suggest that direct genetic transmission is the dominant influence on BMI, while results are consistent with small genetic nurture effects that are driven by the maternal side.
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BibTeX
@misc{pons2026genetic,
title = {{Genetic nurture and direct genetic transmission effects on body mass index across age}},
author = {V. Trindade Pons and N. Gillespie and R. A. J. Smit and J. D. Arias and X. Yin and S. I. Berndt and A. J. Oldehinkel and H. van Loo},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.26361795},
url = {https://www.medrxiv.org/content/10.64898/2026.08.31.26361795v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Genetic nurture and direct genetic transmission effects on body mass index across age
AU - V. Trindade Pons
AU - N. Gillespie
AU - R. A. J. Smit
AU - J. D. Arias
AU - X. Yin
AU - S. I. Berndt
AU - A. J. Oldehinkel
AU - H. van Loo
PY - 2026
DA - 2026/08/31
PB - medRxiv
DO - 10.64898/2026.08.31.26361795
UR - https://www.medrxiv.org/content/10.64898/2026.08.31.26361795v1
AB - Obesity is a growing public health challenge, with body mass index (BMI) influenced by both genetic and environmental factors. While the role of direct genetic transmission is well established, evidence for genetic nurture effects, in which parental genotypes impact offspring through the environment, has remained mixed. This study investigates direct genetic transmission and genetic nurture effects on BMI across ages, using parent-offspring trios and pairs from the Dutch Lifelines cohort study (N = 18,897 offspring, aged 8-67 years). We leveraged the latest multi-ancestry BMI polygenic score (PGS) to construct transmitted (PGS-T) and non-transmitted (PGS-NT) polygenic scores, where PGS-NT consists of parental alleles not passed on to offspring and serves as a proxy for genetic nurture. Linear mixed models showed a large effect of PGS-T on offspring BMI ({beta} = 0.416, p < 0.001), corresponding to a 1.85 kg/m{superscript 2} increase per SD increase in PGS-T. PGS-NT had a small but significant effect ({beta} = 0.026, p = 0.013), consistent with a genetic nurture effect accounting for approximately 6.6% of the effect of direct transmission. Parent-of-origin analyses showed that maternal PGS-NT effects were larger than paternal effects. PGS-T interactions with age indicated that direct transmission effects increased in childhood and stabilized in adulthood, while PGS-NT effects remained stable across age. Our findings suggest that direct genetic transmission is the dominant influence on BMI, while results are consistent with small genetic nurture effects that are driven by the maternal side.
ER -