The moderation of the genetic risk for alcohol and drug use disorders in a Swedish national sample by the genetic aptitude for educational attainment

Abstract

Background Does the genetic aptitude for educational attainment (GAEA) moderate the genetic risk for alcohol use disorder (AUD) and drug use disorder (DUD)? Methods In the native Swedish population, born 1960–1980 and followed through 2017 (n = 1 862 435), the family genetic risk score (FGRS) for AUD and DUD and GAEA were calculated from, respectively, the educational attainment and risk for AUD and DUD, of 1st through 5th degree relatives from Swedish national registers. Analyses utilized Aalen's linear hazards models. Results Risk for AUD was robustly predicted by the main effects of FGRSAUD [b = 6.32 (95% CI 6.21–6.43), z = 64.9, p < 0.001) and GAEA [b = −2.90 (2.83–2.97), z = 44.1, p < 0.001] and their interaction [b = −1.93 (1.83–2.03), z = 32.9, p < 0.001]. Results were similar for the prediction of DUD by the main effects of FGRSDUD [b = 4.65 (CI 4.56–4.74), z = 59.4, p < 0.001] and GAEA [−2.08 (2.03–2.13), z = 46.4, p < 0.001] and their interaction [b = −1.58 (1.50–1.66)), z = 30.2, p < 0.001]. The magnitude of the interactions between GAEA and FGRSAUD and FGRSDUD in the prediction of, respectively, AUD and DUD was attenuated only slightly by the addition of educational attainment to the model. Conclusions and relevance The genetic propensity to high educational attainment robustly moderates the genetic risk for both AUD and DUD such that the impact of the genetic liability to AUD and DUD on the risk of illness is substantially attenuated in those with high v. low GAEA. This effect is not appreciably mediated by the actual level of educational attainment. These naturalistic findings could form the basis of prevention efforts in high-risk youth.

Relationship of Family Genetic Risk Score With Diagnostic Trajectory in a Swedish National Sample of Incident Cases of Major Depression, Bipolar Disorder, Other Nonaffective Psychosis, and Schizophrenia

“…Fourth, the FGRS, a family phenotype-based method to assess quantitative genetic risk, has been now widely published, with prior reports demonstrating that this score is not highly sensitive to the various assumptions involved in its calculation, that the correction for cohabitation effects performs appropriately, and the method agrees well with other similar, although statistically distinct, approaches …”

The actions and interactions of family genetic risk scores for alcohol use disorder and major depression on the risk for these two disorders

“…Using methods outlined previously (Kendler, Ohlsson, Sundquist, Edwards, & Sundquist, 2021; Kendler, Ohlsson, Sundquist, & Sundquist, 2021a, 2021b, 2021c, 2021d), we calculated an FGRS for AUD and MD for all individuals in our study cohort—born 1970–1990. Table S2 contains a detailed explanation of the FGRS which we summarize here.…”

“…Third, we have studied a large population cohort of cases of two disorders widely considered to be heterogeneous. We have shown that the FGRS for MD and AUD varies as a function of age of onset and number of recurrences (Kendler, Ohlsson, Bacanu, Sundquist, & Sundquist, 2022; Kendler, Ohlsson, Sundquist, & Sundquist, 2021a, 2021b, 2021c, 2021d) but this has also been shown using more traditional methods (K. S. Kendler, Gatz, Gardner, & Pedersen, 2005) and reflects more quantitative than qualitative differences among affected cases. Furthermore, we had examined, by structural equation modeling, the relationship between AUD with and without medical complications in the Swedish data and showed them to be relatively closely genetically related (Edwards, Sundquist, Sundquist, Kendler, & Larsson Lönn, 2021).…”

“…In this report, using Swedish national registry data including diagnostic information on first through fourth degree relatives, we construct family genetic risk scores (FGRS) (K. S. Kendler, Ohlsson, Sundquist, Edwards, & Sundquist, 2021, Kendler, Ohlsson, Sundquist, & Sundquist, 2021a, 2021b, 2021c, 2021d) for AUD and MD. As detailed below, the FGRS estimates the genetic risk to illness based on the phenotypes of close and more distant biological relatives controlling for their age, sex, birth cohort, and genetic proximity to the proband as well as controlling for cohabitation effects in an effort to assess genetic as opposed to familial‐environmental sources of resemblance.…”

A Review of Parental Bereavement Interventions

“…This change in the “natural order” of life events and untimely loss permanently alter the hopes and dreams parents may have had for their child 2,3 . Parental bereavement is considered distinct from other types; it is more intense when compared with the death of a sibling, mother, or father 4 . After the death of a child, parents experience a loss of identity and connection to the community, which in turn, impacts their health and well-being 5 …”