Advancing Gene Discovery for Substance Use Disorders Using Additional Traits Related to Behavioral Disinhibition
Poore, H. E.; Chatzinakos, C.; Mallard, T. T.; Sanchez-Roige, S.; Aliev, F.; Hatoum, A.; Waldman, I. D.; Palmer, A. A.; Harden, K. P.; Barr, P. B.; Dick, D. M.
Show abstract
Ongoing efforts to identify genes involved in substance use disorders (SUDs) often focus on individual disorders despite high rates of co-occurrence with each other and other externalizing traits. Here, we investigate whether incorporating data on other externalizing traits can boost power to detect without sacrificing specificity of SUD genetic signal. We used multivariate genomic analyses and downstream biological annotation and genetic association analyses to explore this question. We found that joint analysis of SUDs and other externalizing traits resulted in increased insights into the neurobiology of broad and substance-specific SUD risk. We found no evidence of loss of specificity for SUD genetic signal but note improvements in our ability to characterize the neurobiology of broad and substance-specific SUD genetic effects. Our findings suggest that genetic risk for SUDs operates largely via pathways shared with other behaviors characterized by behavioral disinhibition, with additional substance-specific risk, and that modeling this shared disposition improves gene discovery.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Genetic Heterogeneity Across Dimensions of Alcohol Use Behaviors 96%
- Multivariate GWAS elucidates the genetic architecture of alcohol consumption and misuse, corrects biases, and reveals novel associations with disease 96%
- Genetic underpinnings of the transition from alcohol consumption to alcohol use disorder: shared and unique genetic architectures in a cross-ancestry sample 95%
Similar papers in this journal
- Neurogenetic and multi-omic sources of overlap among sensation seeking, alcohol consumption, and alcohol use disorder 97%
- Genetic liability for substance use associated with medical comorbidities in electronic health records of African- and European-ancestry individuals 96%
- Genome-wide analyses reveal novel opioid use disorder loci and genetic overlap with schizophrenia, bipolar disorder, and major depression 95%
Similar papers in this journal
- Distinguishing clinical and genetic risk factors for suicidal ideation and behavior in a diverse hospital population 94%
- Polygenic scores for tobacco use provide insights into systemic health risks in a diverse EHR-linked biobank in Los Angeles 94%
- Are psychiatric disorders risk factors for COVID-19 susceptibility and severity? a two-sample, bidirectional, univariable and multivariable Mendelian Randomization study 94%
Similar papers in this journal
- Predicting Substance Use Disorders: A Multifactorial Risk Index Combining Clinical, Environmental, and Genetic Risk Factors 98%
- Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium 96%
- Genome-wide association study of problematic opioid prescription use in 132,113 23andMe research participants of European ancestry 95%
Similar papers in this journal
- Novel insights into the common heritable liability to addiction: a multivariate genome-wide association study 97%
- Multi-omic network analysis identifies dysregulated neurobiological pathways in opioid addiction 94%
- GWAS of Over 427,000 Individuals Establishes GABAergic and Synaptic Molecular Pathways as Key for Cognitive Executive Functions 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.