The aggregate effect of rare nonsynonymous SNPs was significant for the illicit drug phenotype, with marginal effects for the other phenotypes. Most applications of GCTA rely on the relationship between tagged SNPs on a genome-wide array and untyped causal variants. For rare nonsynonymous variants we anticipate only very weak, or nonexistent, linkage disequilibrium, which allows the tentative conclusion that nonsynonymous variants typed on the exome chip are directly associated with illicit drug use in this community-representative sample, and awaits replication elsewhere.
