Heritability estimation of cognitive phenotypes in the ABCD Study® using mixed models

Twin and family studies have historically aimed to partition phenotypic variance into components corresponding to additive genetic effects (A), common environment (C), and unique environment (E). Here we present the ACE Model and several extensions in the Adolescent Brain Cognitive Development□ Study (ABCD Study®), employed using the new Fast Efficient Mixed Effects Analysis (FEMA) package. In the twin sub-sample (n = 924, 462 twin pairs), heritability estimates were similar to those reported by prior studies for height (twin heritability = 0.86) and cognition (twin heritability from 0.00 to 0.61), respectively. Incorporating measured genetic relatedness and using the full ABCD Study® sample (n = 9,742) led to narrower confidence intervals for all parameter estimates. By leveraging the sparse clustering method used by FEMA to handle genetic relatedness only for participants within families, we were able to take advantage of the diverse distribution of genetic relatedness within the ABCD Study® sample.