| Title: | Polygenic overlap of substance use behaviors and disorders with externalizing and internalizing problems independent of genetic correlations |
| Journal: | Psychological Medicine |
| Published: | 31 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40162501/ |
| DOI: | https://doi.org/10.1017/s0033291725000108 |
Publication 15953
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Abstract
BACKGROUND: Externalizing and internalizing pathways may lead to the development of substance use behaviors (SUBs) and substance use disorders (SUDs), which are all heritable phenotypes. Genetic correlation studies have indicated differences in the genetic susceptibility between SUBs and SUDs. We investigated whether these substance use phenotypes are differently related to externalizing and internalizing problems at a genetic level.</p>
METHODS: We analyzed data from genome-wide association studies (GWAS) of four SUBs and SUDs, five externalizing traits, and five internalizing traits using the bivariate causal mixture model (MiXeR) to estimate genetic overlap beyond genetic correlation.</p>
RESULTS: Two distinct patterns were found. SUBs demonstrated high genetic overlap but low genetic correlation of shared variants with internalizing traits, suggesting a pattern of mixed effect directions of shared genetic variants. Conversely, SUDs and externalizing traits exhibited considerable genetic overlap with moderate to high positive genetic correlation of shared variants, suggesting concordant effect direction of shared risk variants.</p>
CONCLUSIONS: These results highlight the importance of the externalizing pathway in SUDs as well as the limited role of the internalizing pathway in SUBs. As MiXeR is not intended for the identification of specific genes, further studies are needed to reveal the underlying shared mechanisms of these traits.</p>
7 Keywords
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Multifactorial Inheritance
- Phenotype
- Substance-Related Disorders
10 Authors
- Laila Al-Soufi
- Guy Hindley
- Linn Rødevand
- Alexey A. Shadrin
- Piotr Jaholkowski
- Vera Fominykh
- Romain Icick
- Markos Tesfaye
- Javier Costas
- Ole A. Andreassen
1 Application
| Application ID | Title |
|---|---|
| 27412 | Boosting the power of GWAS using novel statistical tools |
Enabling scientific discoveries that improve human health