Differential patterns of genetic overlap between inattention and four neurocognitive factors

Purpose: Twin and family studies indicate that individual differences in inattention and neurocognitive functioning are heritable, ranging from 50-80% across adolescence. There is also evidence for moderate genetic overlap... [ view full abstract ]

Purpose: Twin and family studies indicate that individual differences in inattention and neurocognitive functioning are heritable, ranging from 50-80% across adolescence. There is also evidence for moderate genetic overlap (64%) between inattention and at least one aspect of neurocognitive functioning, reaction time variability. Adolescence is a period of rapid growth in neurocognitive functioning, yet a comprehensive understanding of the patterns of genetic overlap between inattention and multiple aspects of neurocognitive functioning during this period of development is lacking. The present study investigated: (1) the heritability of inattention and four aspects of neurocognitive functioning (memory, social cognition, executive function, complex cognition) based on additive genome-wide effects; and (2) the degree to which genetic effects are shared between inattention and each of the four aspects of neurocognitive functioning.

Participants and Measures: Genome-wide data were drawn from 3563 unrelated children and adolescents (ages 8-21 years) of European Ancestry enrolled in the Philadelphia Neurodevelopmental Cohort and imputed. 5,360,405 biallelic single nucleotide polymorphisms [SNPs] were retained following imputation and quality control. Participants (for children ages 18+) or their parents (for participants ages 8-17) reported on six inattention questions drawn from the Kiddie Schedule for Affective Disorders and Schizophrenia (adapted) interview, and completed a computerized neurocognitive battery consisting of nine tasks measuring efficiency (response speed, accuracy) across the four neurocognitive domains.

Approach: Factor analysis of the six symptoms of inattention revealed a single dimension of inattention. Confirmatory factor analysis of the neurobehavioral data replicated the four-factor solution previously demonstrated in Moore et al., 2015. Genomic-relatedness-matrix restricted maximum likelihood estimation (GREML) was used to determine the proportion of variance in each phenotype attributable to additive genetic variance. Bivariate GREML was used to examine the genetic correlations (r_G-SNP) between inattention and each neurocognitive domain. Genome-wide association (GWA) analyses (adjusted for multiple testing) were performed to identify genetic variants associated with inattention and each neurocognitive trait.

Results: Common SNPs explained 20% (SE=.08, p < .01) of individual differences in inattention; 17% (SE=.08, p < .05) in memory, 13% (SE=.08, p < .05) in social cognition, 25% (SE=.08, p < .01) in executive function, and 24% (SE=.08, p < .01) in complex cognition. Bivariate analyses indicated that genetic overlap between inattention and social cognition was high (r_G-SNP= .67, SE=.37, p<.01), whereas the genetic correlations between inattention and the other neurocognitive domains were nonsignificant. No single genetic variant for any trait was significant at the GWA level of p < 10^-8.

Conclusions: Modest genetic influences on individual differences in inattention and neurobehavior were observed. Common additive genetic effects explained the overlap between inattention and social cognition. That is, the same genes that influence inattention also contribute to more efficient social cognition. Potential reasons for this overlap and implications will be discussed.

Reference: Moore, T. M., Reise, S. P., Gur, R. E., Hakonarson, H., & Gur, R. C. (2015). Psychometric properties of the Penn Computerized Neurocognitive Battery. Neuropsychology, 29(2), 235-246.