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 between 0.00 and 0.61), respectively. Incorporating SNP-derived 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. ### Competing Interest Statement Dr. Dale reports that he was a Founder of and holds equity in CorTechs Labs, Inc., and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. He receives funding through research grants from GE Healthcare to UCSD. The terms of these arrangements have been reviewed by and approved by UCSD in accordance with its conflict of interest policies. The remaining authors have no conflicts of interest.