Genetic Risk Factors for Poor Cognitive Development in Children With Low Birth Weight

Abstract

Low birth weight is an ongoing public health problem with severe consequences for those affected, including early morbidity and mortality and elevated risk for lifelong deficits in cognitive function. These deficits can be ameliorated by early intervention in many cases. To contribute to criteria for earlier identification of at-risk children prior to the onset of delays or deficits, we examined relationships between three gene candidates— SLC6A4, BDNF, COMT—and cognitive outcomes at school age in a secondary analysis of existing data from a nationally representative cohort. Single nucleotide polymorphism rs4074134, a variant of BDNF, and a rare insertion/deletion in the intron region of SLC6A4 were significant predictors of cognitive performance. Our final model predicted 17% of the variance in composite cognitive test scores among children with low birth weight at school age ( F = 96.36, p < .001, R 2 = .17). Specifically, children homozygous for cytosine at rs4074134 scored .62 standard deviations higher on a measure of global cognition than children with one or more thymine. Similarly, children with an extra-long copy number variant of SLC6A4 scored .88 standard deviations higher than children who had one or more short forms of the gene. These findings support the potential for an approach to identifying children with low birth weights who are most at need of early intervention services. Future research should focus on validation of these findings in an independent sample and confirmation of the biological mechanisms through which these genes influence cognitive development.