Although alcohol use disorder (AUD) is associated with future risk for psychosocial dysfunction, the degree to which this arises from a direct causal effect of AUD on functioning v. from correlated risk factors (also known as confounders) is less clearly established.

AUD was assessed from Swedish medical, criminal and pharmacy registries. In a large general population cohort, using Cox proportional hazard and regression models, we predicted from the onset of AUD four outcomes: early retirement, unemployment, social assistance, and individual income. We then examined the degree to which these associations were attenuated by relevant confounders as well as by the use of discordant cousin, half-sibling, full-sibling, and monozygotic twin pairs.

In males, AUD most strongly predicted social assistance [hazard ratio (HR) 8.27, 95% confidence interval (CI) 7.96–8.59], followed by early retirement (HR 5.63, 95% CI 5.53–5.72) and unemployment (HR 2.75, 95% CI 2.65–2.85). For income at age 50, AUD was associated with a decrease in income of 0.24 s.d.s (95% CI −0.25 to −0.23). Results were similar in females. Modest to moderate attenuation of these associations was seen in both sexes after the addition of relevant covariates. These associations were reduced but remained robust in discordant co-relative pairs, including monozygotic twins.

Our results suggest that AUD has a causal impact on a range of measures reflective of psychosocial dysfunction. These findings provide strong support for the drift hypothesis. However, some of the associations between AUD and dysfunction appear to be non-causal and result from shared risk factors, many of which are likely familial.

Although cannabis abuse (CA) is known to be associated with schizophrenia, the causal nature of this association is unclear, with prodromal effects complicating its interpretation.

From Swedish national registry databases, we used a co-relative case–control design with full-sibling, half-sibling and first-cousin comparisons, alongside a general Swedish population sample. Using ICD codes, 5456 individuals with an initial diagnosis of schizophrenia (2000–2010) were matched with five schizophrenia-free controls. We further identified first-cousin, half-sibling and full-sibling pairs discordant for CA and statistically extrapolated results for discordant monozygotic (MZ) twins.

Within the general Swedish population, CA was strongly associated with later schizophrenia [odds ratio (OR) 10.44, 95% confidence interval (CI) 8.99–12.11]. This association was substantially attenuated both by increasing temporal delays between CA exposure and schizophrenia diagnosis and by controlling for increasing degrees of familial confounding. Extrapolated discordant MZ pairs suggested that fully controlling for confounding familial factors reduced the association between CA and later schizophrenia to more modest levels (ORs of approximately 3.3 and 1.6 with 3- and 7-year temporal delays respectively). Opiate, sedative, cocaine/stimulant and hallucinogen abuse were also strongly associated with subsequent schizophrenia in the general population. After controlling for familial confounding, only cocaine/stimulant exposure remained associated.

CA has an appreciable causal impact on future risk for schizophrenia. However, population-based estimates of cannabis–schizophrenia co-morbidity substantially overestimate their causal association. Predictions of the cases of schizophrenia that might be prevented by reduced cannabis consumption based on population associations are therefore likely to be considerably overestimated.

Risk for drug abuse (DA) is strongly associated with neighborhood social deprivation (SD). However, the causal nature of this relationship is unclear.

Three Swedish population-based cohorts were followed up over 5 years for incident registration of DA in medical, legal or pharmacy records. In each cohort, we examined the SD–DA association, controlling carefully for individual socio-economic status (SES) with multiple measures, in the entire sample and among pairs of first cousins, paternal and maternal half-siblings, full siblings and monozygotic (MZ) twins discordant for SD exposure. The number of informative relative pairs ranged from 6366 to 166 208.

In all cohorts, SD was prospectively related to risk for incident DA. In relative pairs discordant for SD exposure, the SD–DA association was similar to that seen in the entire population in cousins, half-siblings, full siblings and MZ twins. Eliminating subjects who were residentially unstable or had DA in the first two follow-up years did not alter this pattern. When divided by age, in the youngest groups, the SD–DA association was weaker in siblings than in the entire population.

Across three cohorts, controlling for individual SES and confounding familial factors, SD prospectively predicted risk for incident DA registration. These results support the hypothesis that the SD–DA association is in part causal and unlikely to result entirely from personal attributes, which both increase risk for DA and cause selection into high SD environments. At least part of the SD–DA association arises because exposure to SD causes an increased risk of DA.