Heritability estimation of subcortical volumes in a multi-ancestry multi-site cohort study
Christian Coffman, Eric Feczko, Bart Larsen, Brenden Tervo-Clemmens, Gregory Conan, Jacob T. Lundquist, Audrey Houghton, Lucille A. Moore, Kimberly Weldon, Rae McCollum, Begim Fayzullobekova, Thomas J. Madison, Eric Earl, Oscar Miranda Dominguez, Damien A. Fair, Saonli BasuAbstract
Heritability of regional subcortical brain volumes (rSBVs) quantifies the contribution of genetic variation to individual differences in subcortical brain morphology during neurodevelopment. rSBVs are highly heritable in adults but are not well characterized in adolescents. The Adolescent Brain Cognitive Development study (ABCD), collected across 21 US sites, provides data to characterize the heritability of subcortical structures in adolescence. However, in a multi-site multi-ancestry study, such as ABCD, site-specific effects may co-occur with genetic effects, which can bias heritability estimates. Existing methods that adjust for site effects require additional steps and can lead to inconsistent estimates. We propose a random-effect model-based MOM approach to estimate heritability that is a single-step asymptotically consistent estimator even when ancestries are differentially distributed across sites. Our approach performed well under a wide range of simulations. The proposed approach yielded heritability estimates similar to previous results derived from single-site studies and studies on different age groups, with the cerebellar cortex and hippocampus showing the highest estimated heritability ( > 50%).