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Genetic variation associated with diminished dopamine neurotransmission predicts delay in motor development in extremely low birth weight infants
Worley, G., Erickson, S. W., Gustafson, K., Nikolova, Y., Belsky, D., Goldstein, R., Levy, J., McDonald, S. A., Page, G. P., Ashley-Koch, A., & Cotten, M. (2019). Genetic variation associated with diminished dopamine neurotransmission predicts delay in motor development in extremely low birth weight infants. Developmental Medicine and Child Neurology, 61(Suppl. 3), 6. Article A7.
Scientific Presentation Thursday, September 19, 2019: Free Paper Session A: Genetics
Background and Objective(s)
Genetic variation associated with dopamine neurotransmission has been related to motor learning in adults and in children with unilateral Cerebral Palsy receiving constraint‐induced movement therapy in a research study. Motor learning is integral to motor development. Therefore, we sought to determine if genetic variation associated with diminished dopamine neurotransmission predicted delay in motor development in extremely low birth weight (ELBW) infants, a high risk population for motor impairment.
Study Design
Longitudinal study of a convenience cohort.
Study Participants and Settings
Participants were 498 ELBW infants from 16 neonatal intensive care units in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network who were enrolled in a longitudinal study, had genome‐wide genotyping in infancy, and had a standard neurodevelopmental evaluation at 18–22 months corrected age.
Materials and Methods
A polygenic risk score was created to combine into one variable the influences on dopamine neurotransmission of seven alleles for diminished dopamine neurotransmission, by summing the number present in each infant (range=0–14). The outcome variables were the Psychomotor Development Index and the Mental Development Index, measure of motor and cognitive development respectively, of the Bayley Scales of Infant Development II. The linear regression model was adjusted for seven clinical and four genetic ancestry covariates. An effect interaction model of sex‐by‐polygenic risk score was fitted with an interaction term and modification of effect on the Psychomotor Index evaluated by the likelihood‐ratio test.
Results
The polygenic risk score was inversely related to the Psychomotor Development Index (p =0.011). Each one point increase in the polygenic risk score resulted in an average decrease in the Psychomotor Development Index of 1.37 points. Sex did not modified the effect of the polygenic risk score on the Psychomotor Development Index (p =0.61). The polygenic risk score was not related to the Mental Development Index (p =0.299).
Conclusions or Significance
Genetic variation favoring diminished dopamine neurotransmission was an independent risk factor associated with delay in motor development, but not cognitive development, in ELBW infants. This is a novel association with potential research implications. It is unlikely to be an explanation for the worse motor development of premature males.
