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Early DNA methylation at the NGFI-A binding site of the NR3C1 1F promoter predicts cognitive functions at age five: evidence from the Parents as Teachers intervention in the ZEPPELIN study

Gardini, E. S.; Neuhauser, A.; Schaub, S.; Kalkusch, I.; Rodcharoen, P.; Ehlert, U.; Lanfranchi, A.; Turecki, G.; Klaver, P.

2026-02-24 psychiatry and clinical psychology
10.64898/2026.02.22.26346845 medRxiv
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BackgroundThe present study examines the link between DNA methylation at the nerve growth factor-induced protein A (NGFI-A) binding domain of the NR3C1 1F promoter and later cognitive functions in children from families living in disadvantaged psychosocial conditions. MethodsParticipants were 132 children who took part in a Swiss Parents as Teachers (PAT) randomized controlled trial (72 in the intervention group, 60 in the control group). DNA methylation was quantified from saliva samples collected at age three using sodium bisulfite next-generation sequencing (NGS). Cognitive functions were assessed at age five using the SON-R 2.5-7 Intelligence Test. Results(a) DNA methylation at age three predicted lower IQ at age five through increased concentration problems; (b) participation in the three-year PAT program predicted lower methylation levels at the end of the intervention; and (c) early life stressors predicted lower IQ through increased methylation and concentration problems with descriptively stronger effects in the control group. ConclusionsThese findings demonstrate a link between early DNA methylation at the NGFI-A binding site of the NR3C1 1F promoter and later cognitive functions in children and highlight the role of early life stressors and the PAT intervention in shaping these associations.

Published in PLOS One · not in our set (fewer than 10 published preprints to learn from) · training set

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