Kenneth S Kendler1,2, Henrik Ohlsson3, Abigail A Fagan4, Paul Lichtenstein5, Jan Sundquist4,6,7,8, Kristina Sundquist4,6,7,8. 1. Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond. 2. Department of Psychiatry, Virginia Commonwealth University, Richmond. 3. Center for Primary Health Care Research, Lund University, Malmö, Sweden. 4. Department of Sociology, Criminology & Law, University of Florida, Gainesville. 5. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. 6. Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, New York. 7. Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York. 8. Center for Community-Based Healthcare Research and Education, Department of Functional Pathology, School of Medicine, Shimane University, Matsue, Japan.
Abstract
Importance: Low academic achievement (AA) in childhood and adolescence is associated with increased substance use. Empirical evidence, using longitudinal epidemiologic data, may provide support for interventions to improve AA as a means to reduce risk of drug abuse (DA). Objective: To clarify the nature of the association between adolescent AA and risk of DA by using instrumental variable and co-relative analysis designs. Design, Setting, and Participants: This study, assessing nationwide data from individuals born in Sweden between 1971 and 1982, used instrumental variable and co-relative analyses of the association between AA and DA. The instrument was month of birth. Co-relative analyses were conducted in pairs of cousins (263 222 pairs), full siblings (154 295), and monozygotic twins (1623) discordant for AA, with raw results fitted to a genetic model. The AA-DA association was modeled using Cox regression. Data analysis was conducted from October 2017 to January 2018. Exposures: Academic achievement assessed at 16 years of age (for instrumental variable analyses), and estimated discordance in AA in pairs of monozygotic twins (for co-relative analyses). Main Outcomes and Measures: Drug abuse registration in national medical, criminal, or pharmacy registries. Results: This instrumental variable analysis included 934 462 participants (478 341 males and 456 121 females) with a mean (SD) age of 34.7 (4.3) years at a mean follow-up of 19 years. Earlier month of birth was associated with a linear effect on AA, with the regression coefficient per month equaling -0.0225 SDs (95% CI, -0.0231 to -0.0219). Controlling for AA, month of birth had no association with risk of DA (hazard ratio [HR], 1.000; 95% CI, 0.997-1.004). Lower AA had a significant association with risk of subsequent DA registration (HR per SD, 2.33; 95% CI, 2.30-2.35). Instrumental variable analysis produced a substantial but modestly attenuated association (HR, 2.04; 95% CI, 1.75-2.33). Controlling for modest associations between month of birth and parental educational status and DA risk reduced the association to a HR of 1.92 (95% CI, 1.67-2.22). The genetic model applied to the results of co-relative analyses fitted the observed data well and estimated the AA-DA association in monozygotic twins discordant for AA to equal a HR of 1.79 (95% CI, 1.64-1.92). Conclusions and Relevance: Two different methodological approaches with divergent assumptions both produced results consistent with the hypothesis that the significant association observed between AA at 16 years of age and risk of DA into middle adulthood may be causal. These results provide empirical support for efforts to improve AA as a means to reduce risk of DA.
Importance: Low academic achievement (AA) in childhood and adolescence is associated with increased substance use. Empirical evidence, using longitudinal epidemiologic data, may provide support for interventions to improve AA as a means to reduce risk of drug abuse (DA). Objective: To clarify the nature of the association between adolescent AA and risk of DA by using instrumental variable and co-relative analysis designs. Design, Setting, and Participants: This study, assessing nationwide data from individuals born in Sweden between 1971 and 1982, used instrumental variable and co-relative analyses of the association between AA and DA. The instrument was month of birth. Co-relative analyses were conducted in pairs of cousins (263 222 pairs), full siblings (154 295), and monozygotic twins (1623) discordant for AA, with raw results fitted to a genetic model. The AA-DA association was modeled using Cox regression. Data analysis was conducted from October 2017 to January 2018. Exposures: Academic achievement assessed at 16 years of age (for instrumental variable analyses), and estimated discordance in AA in pairs of monozygotic twins (for co-relative analyses). Main Outcomes and Measures: Drug abuse registration in national medical, criminal, or pharmacy registries. Results: This instrumental variable analysis included 934 462 participants (478 341 males and 456 121 females) with a mean (SD) age of 34.7 (4.3) years at a mean follow-up of 19 years. Earlier month of birth was associated with a linear effect on AA, with the regression coefficient per month equaling -0.0225 SDs (95% CI, -0.0231 to -0.0219). Controlling for AA, month of birth had no association with risk of DA (hazard ratio [HR], 1.000; 95% CI, 0.997-1.004). Lower AA had a significant association with risk of subsequent DA registration (HR per SD, 2.33; 95% CI, 2.30-2.35). Instrumental variable analysis produced a substantial but modestly attenuated association (HR, 2.04; 95% CI, 1.75-2.33). Controlling for modest associations between month of birth and parental educational status and DA risk reduced the association to a HR of 1.92 (95% CI, 1.67-2.22). The genetic model applied to the results of co-relative analyses fitted the observed data well and estimated the AA-DA association in monozygotic twins discordant for AA to equal a HR of 1.79 (95% CI, 1.64-1.92). Conclusions and Relevance: Two different methodological approaches with divergent assumptions both produced results consistent with the hypothesis that the significant association observed between AA at 16 years of age and risk of DA into middle adulthood may be causal. These results provide empirical support for efforts to improve AA as a means to reduce risk of DA.
Authors: C Debra M Furr-Holden; Nicholas S Ialongo; James C Anthony; Hanno Petras; Sheppard G Kellam Journal: Drug Alcohol Depend Date: 2004-02-07 Impact factor: 4.492
Authors: Anna G C Boef; Patrick C Souverein; Jan P Vandenbroucke; Astrid van Hylckama Vlieg; Anthonius de Boer; Saskia le Cessie; Olaf M Dekkers Journal: Pharmacoepidemiol Drug Saf Date: 2016-01-08 Impact factor: 2.890
Authors: Kenneth S Kendler; Henrik Ohlsson; Abigail A Fagan; Paul Lichtenstein; Jan Sundquist; Kristina Sundquist Journal: J Stud Alcohol Drugs Date: 2020-07 Impact factor: 2.582
Authors: Kenneth S Kendler; Henrik Ohlsson; Sean Clouston; Abigail A Fagan; Jan Sundquist; Kristina Sundquist Journal: Psychol Med Date: 2020-01-07 Impact factor: 7.723