Within-family environmental transmission of drug abuse: a Swedish national study

Abstract

CONTEXT Drug abuse (DA) strongly runs in families. Does this result solely from genetic factors or does the family environment contribute? OBJECTIVE To determine the familial environmental contribution to the risk for DA. DESIGN Follow-up in 9 public databases (1961-2009) in siblings and spouses. SETTING Sweden. PARTICIPANTS A total of 137 199 sibling pairs and 7561 spousal pairs containing a proband with DA and matched control probands. MAIN OUTCOME MEASURES Drug abuse recorded in medical, legal, or pharmacy registry records. RESULTS In the best-fit model, which contained significant linear, quadratic, and cubic effects, among full sibling pairs containing a proband with DA, the relative risk for DA in the sibling declined from more than 6.0 for siblings born within 2 years of each other to less than 4.5 when born 10 years apart. Controlling for age differences in full sibling pairs, the hazard rate for DA in a sibling when the affected proband was older vs younger was 1.42 (95% CI, 1.31-1.54). In the best-fit model, which contained significant linear, quadratic, and cubic effects, among spousal pairs containing a proband with DA, the relative risk for DA in the spouse declined from more than 25.0 within 1 year of proband DA registration to 6.0 after 5 years. CONCLUSIONS Controlling for genetic effects by examining only full siblings, sibling resemblance for the risk for DA was significantly greater in pairs closer vs more distant in age. Older siblings more strongly transmitted the risk for DA to their younger siblings than vice versa. After one spouse is registered for DA, the other spouse has a large short-lived increase in DA risk. These results support strong familial environmental influences on DA at various life stages. A complete understanding of the familial transmission of DA will require knowledge of how genetic and familial environmental risk factors act and interact over development.

Figure 1

The relationship between age difference and the risk for drug abuse (DA) among siblings of case probands with DA vs siblings of matched control subjects. We show results, predicted by the best-fit model up to 11 years difference between siblings, for all sibling pairs and the 4 sex combinations: male case/male sibling, male case/female sibling, female case/male sibling, and female case/female sibling.

Figure 2

The cumulative probability of receiving a drug abuse (DA) diagnosis over a 20-year follow-up period for siblings where the older vs younger sibling had DA as predicted from the full Cox model, the results of which are given in Table 2.

Figure 3

The risk for drug abuse (DA) as predicted from a Cox model, the details of which are presented in Table 2, at 20-year follow-up from the diagnosis of DA in the proband. A, The results depict the risk when the male proband with DA is older vs younger than the male sibling, as a function of the age difference between them. B, The results depict the risk when the male proband with DA is older vs younger than the female sibling, as a function of the age difference between them. C, The results depict the risk when the female proband with DA is older vs younger than the female sibling, as a function of the age difference between them. D, The results depict the risk when the female proband with DA is older vs younger than the male sibling, as a function of the age difference between them.

Figure 4

The relative risk of registration for drug abuse (DA) in the spouse of a case proband with DA vs a control proband.