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SUD Risk Predicted by Genetic, Environmental, and Clinical Factors

SUD Risk Predicted by Genetic, Environmental, and Clinical Factors

The This summary includes studiesThis preprint was published but has not been peer-reviewed.

The Key Takeaways

  • The ability to distinguish between individuals with alcohol, drug, or any other substance abuse disorders in young adulthood is limited by genetic, environmental, clinical, and genetic risk factors.

  • The predictive power of polygenic scores and a clinical/environmental/risk index (CERI) was tested by evaluating four longitudinal cohorts. It revealed the association of CERI with DSM-IV guidelines. alcohol dependence, drug dependence, or any other substance dependence.

  • Both problematic alcohol use and externalizing were associated with any substance dependence. The polygenic score for problematic alcohol use was associated with alcohol dependence. While the polygenic score for externalizing was associated with drug dependence, it was also associated with alcohol dependence.

Why this matters

  • There is a great public health need to identify individuals at high risk of developing substance use disorders due to the large financial costs to society, their families, as well as the personal and family consequences.

  • This data analysis provides evidence that each risk factor is a unique indicator of substance abuse disorders in the early adulthood.

  • These data will be combined with expanding information sources to allow for better precision in future screening tools that can identify and intervene for individuals most at risk of developing substance abuse disorders.

Study Design

  • Four longitudinal cohorts were used to evaluate the association of early-life CERI scores and polygenic scores with substance abuse disorders. These cohorts (combined sampling n = 15,134), comprised population samples from three different countries (United States. England. Finland). Two samples also included individuals of European and African descent.

  • The main outcome of a DSM-IV lifetime diagnosis of a substance misuse disorder was the nonmutually exempt categories of alcohol dependence, drug dependency, and any substance dependence (alcohol/other drug or nicotine).

  • The CERI considered 10 early life risk factors for substance abuse disorders. These were compiled to measure risk. The polygenic scores were a composite of the risk alleles that individuals had, weighed against recent genome-wide association studies on substance use disorders. Substance abuse disorders had strong genetic overlap with psychotic, externalizing, and internalizing disorders.

  • A series of nested logistic regression models with pooled data included a baseline model (sex, age, and cohort), a genetic risk model (baseline + polygenic scores), a clinical/environmental risk model (baseline + CERI), and a combined risk model (baseline + polygenic scores + CERI) to assess the predictive accuracy of each model. 

Key Results

  • The CERI model was associated to alcohol dependence, drug dependence, or any substance dependence (odds ratios). [ORs], 1.351.64).

  • The overall predictive power of polygenic score alone was between 1.3% and 2.4%.

  • The polygenic scores of problematic alcohol use were associated to alcohol dependence (OR 1.14), while the polygenic scores for externalizing were linked with drug dependence. (OR 1.14).

  • The polygenic scores of problematic alcohol use and externalizing were correlated with any substance dependence (ORs. 1.111.19).

  • The relative risk ratio for each substance use disorder was 3.829.13 in the top 10% of CERI, and polygenic scores relative the bottom 90%.


  • Individuals of different ancestries were included. However, the polygenic scores for African-ancestry samples were calculated based on a small sample size. Studies of genome-wide associations in large cohorts are required.

  • The measure of environmental risks may not have included all social determinants and risk factors that contribute to substance abuse disorders in populations other non-Hispanic White persons.

  • Not well represented were racially relevant measures and other social and environment measures that are known to be risk factors for substance abuse disorders. 

  • Some risk factors, such as adolescent drug abuse, could have occurred simultaneously with diagnosis. It will be useful to compare samples that include risk factors measured prior to substance use.


  • The authors declare no competing interests.

  • The National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse and the Academy of Finland supported the study. They also supported the Scientific and Technological Research Council of Turkey and the Sigrid Juslius Foundation.

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This is a summary of the preprint research study. “Predicting Substance Use Disorders – A Multifactorial Risk Indicator Combining Clinical, Environmental and Genetic Risk Factors” Written by Peter B. Barr from SUNY Downstate Health Sciences University (New York City) and colleagues on medRxiv. Provided to you by Medscape. This study has not been peer reviewed. The complete text of the study can be found at 

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