In COT studies, genetic and environmental risks are inferred from parent and cotwin history of substance dependence, with outcomes of offspring from a minimum of four groups compared, each with varying degrees of genetic risk and environmental exposure. In the present analysis, these groups include: offspring whose parent is substance dependent (Group 1); offspring of an unaffected parent whose monozygotic (MZ) cotwin is substance dependent (Group 2); offspring of an unaffected parent whose dizygotic (DZ) cotwin is substance dependent (Group 3); and offspring from control families, where neither parent nor cotwin, regardless of zygosity, is substance dependent (Group 4). Hypothesized risks to offspring are summarized in Table 1.
