By middle adulthood (ages 40–59 years), the picture shifts. The mHRs in close relatives were much lower than in the general population but now also substantially greater than unity. This is the picture that would be expected if the AUD-mortality association arose from a mixture of familial confounding and direct causal relationships. Direct causal effects of AUD are likely to be complex and include exposure to high levels of alcohol intake often over long periods, frequent intoxication, and the associated poor judgment in dangerous situations (eg, driving and physical aggression), poor nutrition, increased tobacco and other drug use, social isolation, and poorer health care. Of course, for some of these associations (eg, AUD and social isolation or drug use), causal effects are likely to be bidirectional. Finally, by late adulthood, little difference was seen in the mHRs across the general population and all our samples of discordant relatives including discordant MZ twin pairs. This is the picture expected if the preponderance of the AUD-mortality association arose as a direct result of the AUD itself.
