Peer deviance, parental divorce, and genetic risk in the prediction of drug abuse in a nationwide Swedish sample: evidence of environment-environment and gene-environment interaction

Abstract

Importance: Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA).

Objectives: To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels.

Design, setting, and participants: Studies of future DA registration in 1,401,698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA.

Main outcomes and measures: Drug abuse recorded in medical, legal, or pharmacy registry records.

Results: Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure.

Conclusions and relevance: With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors.

Figure 1. Distribution of Rates of Drug Abuse in Peers

Rates were assessed at the proband age of 15 years across 7738 Small Areas for Market Statistics in Sweden.

Figure 2. Association (Hazard Ratios) Between Peer Deviance and Subsequent Drug Abuse

Figure 3. Results From the Linear Hazard Model

Results include main effects of divorce, peer deviance, and their interaction, as well as the genetic risk score. The excess numbers of new drug abuse cases per 10 000 person-years for those with no parental loss raised in a Small Area for Market Statistics with 0% vs 15% rates of drug abuse in peers were 0 and 35.7, respectively, for a difference of 35.7. For those with parental loss, the figures were 4.4 and 51.2, respectively, for a difference of 46.8.

Figure 4. Results From the Linear Hazard Model With the Main Effects of Genetic Risk, Peer Deviance, and Their Interaction

We examined 5 levels of genetic risk from categories outlined in Table 3: low (no affected relative), moderate (only mother affected), moderately high (all siblings affected), high (father and 50% of siblings affected), and very high (monozygotic co-twin affected). The excess numbers of new drug abuse cases per 10 000 person-years for those with low genetic risk raised in a Small Area for Market Statistics with 0% vs 15% rates of drug abuse in peers were 8.0 and 36.1, respectively, for a difference of 28.1. For those at moderate, moderately high, high, and very high genetic risk, the figures were 21.5 and 59.7 for a difference of 38.2; 34.5 and 82.4 for a difference of 47.9; 51.2 and 111.6 for a difference of 60.4; and 74.8 and 152.8 for a difference of 78.0, respectively.