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Academic Achievement and Drug Abuse Risk Assessed Using Instrumental Variable Analysis and Co-relative Designs

Kendler, Kenneth S. LU ; Ohlsson, Henrik LU ; Fagan, Abigail A. ; Lichtenstein, Paul ; Sundquist, Jan LU and Sundquist, Kristina LU (2018) In JAMA Psychiatry 75(11). p.1182-1188
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 (263222... (More)

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 (263222 pairs), full siblings (154295), 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 934462 participants (478341 males and 456121 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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
JAMA Psychiatry
volume
75
issue
11
pages
1182 - 1188
publisher
American Medical Association
external identifiers
  • scopus:85053188428
  • pmid:30193341
ISSN
2168-622X
DOI
10.1001/jamapsychiatry.2018.2337
language
English
LU publication?
yes
id
084a6a10-a897-48b9-a604-3c305b704caa
date added to LUP
2018-10-24 13:33:17
date last changed
2021-10-06 04:09:53
@article{084a6a10-a897-48b9-a604-3c305b704caa,
  abstract     = {<p>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 (263222 pairs), full siblings (154295), 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 934462 participants (478341 males and 456121 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.</p>},
  author       = {Kendler, Kenneth S. and Ohlsson, Henrik and Fagan, Abigail A. and Lichtenstein, Paul and Sundquist, Jan and Sundquist, Kristina},
  issn         = {2168-622X},
  language     = {eng},
  month        = {09},
  number       = {11},
  pages        = {1182--1188},
  publisher    = {American Medical Association},
  series       = {JAMA Psychiatry},
  title        = {Academic Achievement and Drug Abuse Risk Assessed Using Instrumental Variable Analysis and Co-relative Designs},
  url          = {http://dx.doi.org/10.1001/jamapsychiatry.2018.2337},
  doi          = {10.1001/jamapsychiatry.2018.2337},
  volume       = {75},
  year         = {2018},
}