Social genetic effects for drug use disorder among spouses

Abstract

Aims: Preclinical and human studies suggest that a social partner's genotype may be associated with addiction-related outcomes. This study measured whether spousal genetic makeup is associated with risk of developing drug use disorder (DUD) during marriage and whether the risk associated with a spouse's genotype could be disentangled from potentially confounding rearing environmental effects.

Design: Univariable and multivariable logistic regression analyses.

Setting: Sweden.

Participants: Men and women born between 1960 and 1990 and in opposite-sex first marriages before age 35 (n = 294 748 couples).

Measurements: Outcome was DUD diagnosis (inclusive of opioids, sedatives/hypnotics/anxiolytics, cocaine, cannabis, amphetamine and other psychostimulants, hallucinogens, other drugs of abuse and combinations thereof) obtained from legal, medical and pharmacy registries. The focal predictor was family genetic risk scores for DUD (FGRS-DUD), which were inferred from diagnoses in first- through fifth-degree relatives and weighted by degree of genetic sharing. FGRS-DUD were calculated separately for each partner in a couple.

Findings: Marriage to a spouse with a high FGRS-DUD was associated with increased risk of developing DUD during marriage, OR_males = 1.68 (95% CI = 1.50, 1.88) and OR_females = 1.35 (1.16, 1.56), above and beyond the risk associated with one's own FGRS-DUD. The risk associated with a spouse's FGRS-DUD remained statistically significant after covarying for parental education. As indicated by a series of null interaction effects, there was no evidence that the risk associated with a spouse's FGRS-DUD differed depending on whether the spouse was DUD-affected, probands' probable contact with in-laws and whether the spouse was raised by his/her biological parents or in another home.

Conclusions: There is relatively robust evidence that a person's risk for developing drug use disorder is associated with the genetic makeup of the person's spouse.

Keywords: Drug use disorder; family genetic risk score; marriage; metagenomics; social genetic effects; social transmission.