Genetic investigation of the association between maternal dietary patterns and offspring ADHD

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Abstract
In observational studies, an unhealthy dietary pattern during pregnancy is associated with an increased likelihood of offspring ADHD. We investigated whether such associations may be partly attributable to genetic confounding. Polygenic scores (PGSs) for a healthy dietary pattern were calculated for mother, father, and child trios in the COPSAC 2010 cohort. Diagnoses and trait scores of ADHD were assessed in the children at age 10. Using trio models, we tested whether the association between maternal genetic liability to a healthy dietary pattern and offspring ADHD could be accounted for by genetic confounding. In COPSAC 2010 trio models (N-trio=437), a maternal healthy dietary pattern PGS was associated with reduced ADHD trait score after adjustment for child and paternal dietary pattern PGS, suggesting indirect genetic effects consistent with causal effects from maternal diet. However, this was not replicated in MoBa (N-trio=41 580) or ALSPAC (N-trio=1 211), where direct genetic effect estimates implied an important role for genetic confounding. Collectively, these genetic results indicate a potential pathway by which genetic confounding can inflate observed associations between maternal dietary pattern in pregnancy and offspring ADHD, and do not provide any robust evidence consistent with a causal pathway between the two. These findings should be interpreted in the light of both the limited predictive power of the dietary pattern PGS, which accounted for only a small proportion of pregnancy diet variance, and the multi-faceted nature of diet as an exposure.
Funding Information
  • Lundbeck Foundation (Grant no R16-A1694)
  • Ministeriet Sundhed Forebyggelse (Grant no 903516)
  • Strategiske Forskningsråd (Grant no 0603-00280B)
  • Region Hovedstaden (-)
  • Novo Nordisk (grant agreement No. NNF21OC0068517)
  • Horizon 2020 Framework Programme
  • Norges Forskningsråd (#274611, #336085)
  • Helse Sør-Øst RHF (#2020022, #2019097, #2018059)
  • Helse Sør-Øst RHF (#2022083, #2019097)

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