In Yale-Penn, we identified multivariate gene–environment interactions (Bayes factors, BF > 0) of SI with respect to a gene cluster on chromosome 16 (LCAT, p = 1.82 × 10–7; TSNAXIP1, p = 2.13 × 10−7; CENPT, p = 2.32 × 10−7; PARD6A, p = 5.57 × 10−7) for opioid dependence (BF = 12.2), cocaine dependence (BF = 12.1), nicotine dependence (BF = 9.2), and polysubstance dependence (BF = 2.1). The gene discussed is PARD6A; the disease is cocaine dependence.