Abstract
Overweight in children is strongly associated with parental body mass index (BMI) and overweight. We assessed parental transmitted and non-transmitted genetic contributions to overweight in children from the Danish National Birth Cohort by constructing genetic risk scores (GRSs) from 941 common genetic variants associated with adult BMI and estimating associations of transmitted maternal/paternal and non-transmitted maternal GRS with child overweight. Maternal and paternal BMI (standard deviation (SD) units) had a strong association with childhood overweight [Odds ratio (OR): 2.01 (95% confidence interval (CI) 1.74; 2.34) and 1.64 (95% CI 1.43; 1.89)]. Maternal and paternal transmitted GRSs (SD-units) increased odds for child overweight equally [OR: 1.30 (95% CI 1.16; 1.46) and 1.30 (95% CI 1.16; 1.47)]. However, both the parental phenotypic and the GRS associations may depend on maternal BMI, being weaker among mothers with overweight. Maternal non-transmitted GRS was not associated with child overweight [OR 0.98 (95% CI 0.88; 1.10)] suggesting no specific influence of maternal adiposity as such. In conclusion, parental transmitted GRSs, based on adult BMI, contribute to child overweight, but in overweight mothers other genetic and environmental factors may play a greater role.
Highlights
The combined effects in parents and their offspring of genetic factors, shared environmental exposures and lifestyle, in itself being determined by genetic and environmental factors, make it challenging to distinguish and quantify the impact of these factors[15], but the rapidly expanding series of genetic variants associated with body mass index (BMI) improves the opportunities to disentangle the effects
This study design allowed us to assess to what extent the parental transmitted genetic risk scores (GRSs) contribute to child overweight and to the parent-child associations of overweight, whether maternal non-transmitted variants are associated with child overweight, and to explore if maternal overweight modifies the maternal and paternal genetic contributions
We found that the association of maternal BMI, GRS, and transmitted GRS as well as child GRS with childhood overweight was stronger among the REF group than among the mothers with overweight (MO-OW) group, whereas the associations with paternal BMI and transmitted GRS were less clear, indicating that maternal overweight may diminish these effects (Table 5)
Summary
The combined effects in parents and their offspring of genetic factors, shared environmental exposures and lifestyle, in itself being determined by genetic and environmental factors, make it challenging to distinguish and quantify the impact of these factors[15], but the rapidly expanding series of genetic variants associated with BMI improves the opportunities to disentangle the effects. Building genetic risk scores (GRSs) by summation over this large number of genetic variants can provide strong genetic probes[19], especially in settings, e.g. within families, where a the major part of the contribution to the variance in BMI from differences between families is controlled for. Utilizing such GRSs to investigate the maternal and paternal genetic effects and the specific maternal effects is blurred by the transmission of only a random half of the parental alleles. This study design allowed us to assess to what extent the parental transmitted GRSs contribute to child overweight and to the parent-child associations of overweight, whether maternal non-transmitted variants are associated with child overweight, and to explore if maternal overweight modifies the maternal and paternal genetic contributions
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