Lotfi Khemiri1, Henrik Larsson2, Ralf Kuja-Halkola2, Brian M D'Onofrio2,3, Paul Lichtenstein2, Nitya Jayaram-Lindström1, Antti Latvala2,4. 1. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden. 2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 3. Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA. 4. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Abstract
AIMS: To assess whether parental substance use disorder (SUD) is associated with lower cognitive ability in offspring, and whether the association is independent of shared genetic factors. DESIGN: A population family-based cohort study utilizing national Swedish registries. Linear regression with increased adjustment of covariates was performed in the full population. In addition, the mechanism of the association was investigated with children-of-sibling analyses using fixed-effects regression with three types of sibling parents with increasing genetic relatedness (half-siblings, full siblings and monozygotic twins). SETTING AND PARTICIPANTS: A total of 3 004 401 people born in Sweden between 1951 and 1998. MEASUREMENTS: The exposure variable was parental SUD, operationalized as having a parent with life-time SUD diagnosis or substance-related criminal conviction in the National Patient Register or Crime Register, respectively. Outcomes were cognitive test score at military conscription and final school grades when graduating from compulsory school. Covariates included in the analyses were sex, birth year, parental education, parental migration status and parental psychiatric comorbid diagnoses. FINDINGS: In the full population, parental SUD was associated with decreased cognitive test stanine scores at conscription [4.56, 95% confidence interval (CI) = 4.55-4.57] and lower Z-standardized school grades (-0.43, 95% CI = -0.43 to -0.42) compared to people with no parental SUD (cognitive test: 5.17, 95% CI = 5.17-5.18; grades: 0.09, 95% CI = 0.08-0.09). There was evidence of a dose-response relationship, in that having two parents with SUD (cognitive test: 4.17, 95% CI = 4.15-4.20; grades: -0.83, 95% CI = -0.84 to -0.82) was associated with even lower cognitive ability than having one parent with SUD (cognitive test: 4.60, 95% CI = 4.59-4.60; grades: -0.38, 95% CI = -0.39 to -0.380). In the children-of-siblings analyses when accounting for genetic relatedness, these negative associations were attenuated, suggestive of shared underlying genetic factors. CONCLUSIONS: There appear to be shared genetic factors between parental substance use disorder (SUD) and offspring cognitive function, suggesting that cognitive deficits may constitute a genetically transmitted risk factor in SUD.
AIMS: To assess whether parental substance use disorder (SUD) is associated with lower cognitive ability in offspring, and whether the association is independent of shared genetic factors. DESIGN: A population family-based cohort study utilizing national Swedish registries. Linear regression with increased adjustment of covariates was performed in the full population. In addition, the mechanism of the association was investigated with children-of-sibling analyses using fixed-effects regression with three types of sibling parents with increasing genetic relatedness (half-siblings, full siblings and monozygotic twins). SETTING AND PARTICIPANTS: A total of 3 004 401 people born in Sweden between 1951 and 1998. MEASUREMENTS: The exposure variable was parental SUD, operationalized as having a parent with life-time SUD diagnosis or substance-related criminal conviction in the National Patient Register or Crime Register, respectively. Outcomes were cognitive test score at military conscription and final school grades when graduating from compulsory school. Covariates included in the analyses were sex, birth year, parental education, parental migration status and parental psychiatric comorbid diagnoses. FINDINGS: In the full population, parental SUD was associated with decreased cognitive test stanine scores at conscription [4.56, 95% confidence interval (CI) = 4.55-4.57] and lower Z-standardized school grades (-0.43, 95% CI = -0.43 to -0.42) compared to people with no parental SUD (cognitive test: 5.17, 95% CI = 5.17-5.18; grades: 0.09, 95% CI = 0.08-0.09). There was evidence of a dose-response relationship, in that having two parents with SUD (cognitive test: 4.17, 95% CI = 4.15-4.20; grades: -0.83, 95% CI = -0.84 to -0.82) was associated with even lower cognitive ability than having one parent with SUD (cognitive test: 4.60, 95% CI = 4.59-4.60; grades: -0.38, 95% CI = -0.39 to -0.380). In the children-of-siblings analyses when accounting for genetic relatedness, these negative associations were attenuated, suggestive of shared underlying genetic factors. CONCLUSIONS: There appear to be shared genetic factors between parental substance use disorder (SUD) and offspring cognitive function, suggesting that cognitive deficits may constitute a genetically transmitted risk factor in SUD.
Authors: Florien Meulewaeter; Elisabeth De Schauwer; Sarah S W De Pauw; Wouter Vanderplasschen Journal: Front Psychiatry Date: 2022-02-02 Impact factor: 4.157