The role of remission in the intergenerational transmission of alcohol use disorder: Course, context, and offspring outcomes

Project Summary Abstract
The economic, physical and emotional harms borne by AUD-affected families are great. 7.5 million U.S. children
live with an AUD-affected parent and have increased risk for poverty, abuse and neglect in addition to heightened
genetic risk for alcohol problems. Remission from AUDs is common, but this is seldom acknowledged in
research on the costs and consequences of AUDs. Up to 50% of individuals with lifetime AUDs experience
remission, many within 14 years of AUD onset and many during prime child-bearing and child-rearing years. Our
broad goal for this project is to comprehensively probe the remission phenotype and its role in the
intergenerational transmission of AUDs. We will use family-based data from the Collaborative Study on the
Genetics of Alcoholism, a study ongoing since 1989 that recruits families with heightened risk for AUDs and
more than 15,000 ever-drinkers. Because of COGA's high-risk design, there are sufficient numbers of AUD-
affected individuals (N=7724, 49%), and therefore available for remission, to permit this examination of remission
within families and its effect on offspring outcomes. In Aim 1 we will use survival analysis and person-centered
longitudinal methods to characterize the course of AUD and remission (chronic AUD, stable or relapsing
remission, movement through different types of remission [abstinent, non-abstinent]) and identify demographic
and behavioral antecedents and sequalae of remission and relapse (marital status, children, employment,
income, education, co-occurring substance and psychiatric disorders, treatment). In exploratory analysis, we will
construct a measure of family density of remission and test its association with AUD and remission. Because the
genetic and environmental factors that influence AUD and remission do not entirely overlap, we expect this
measure to have a small but significant association with the probability of not developing AUD and with the
likelihood of remission in individuals with AUD, independent of polygenic risk (PRS) for AUD. In Aim 2, we use
biological parent-offspring pairs to characterize the familial environment of adolescent offspring (household
income, parental marital status, childhood trauma) and variation in adolescent and adult offspring alcohol use
and AUD/remission as a function of parental AUD/remission. Sibling comparisons will delineate for whom
parental remission is likely to have the greatest impact, while providing rigorous control for potential genetic and
environmental confounders shared by siblings. The proposal is innovative in its focus on resilience, rather than
risk, in individuals and families; in its extension of the influence of parental AUD/remission into young and mid-
adulthood; and in its use of a genetically-informed approach to understanding the role of remission in the
intergenerational transmission of AUDs. Results can provide leverage for clinicians to encourage recovery in
patients who are or plan to become parents and will contribute to improved prevention and treatment efforts to
reduce the intergenerational transmission of AUDs and associated problems.

Grant Number: 5R01AA030563-03
NIH Institute/Center: NIH
Principal Investigator: ARPANA AGRAWAL