Multivariate genomic analysis of 1.5 million people identifies genes related to addiction, antisocial behavior, and health
Karlsson Linner, R.; Mallard, T. T.; Barr, P. B.; Sanchez-Roige, S.; Madole, J. W.; Driver, M. N.; Poore, H. E.; Grotzinger, A. D.; Tielbeek, J. J.; Johnson, E. C.; Liu, M.; Zhou, H.; Kember, R.; Pasman, J. A.; Verweij, K. J. H.; Liu, D.; Vrieze, S.; Kranzler, H.; Gelernter, J.; Mullan Harris, K.; Tucker-Drob, E. M.; Waldman, I. D.; Palmer, A. A.; Harden, K. P.; Koellinger, P. D.; Dick, D. M.
Show abstract
Behaviors and disorders related to self-regulation, such as substance use, antisocial conduct, and ADHD, are collectively referred to as externalizing and have a shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5 million people, our approach is statistically more powerful than single-trait analyses and identifies more than 500 genetic loci. The identified loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results captures variation in a broad range of behavioral and medical outcomes that were not part of our genome-wide analyses, including traits that until now lacked well-performing polygenic scores, such as opioid use disorder, suicide, HIV infections, criminal convictions, and unemployment. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental condition.
Matching journals
The top 2 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Genome-wide landscape of RNA-binding protein dysregulation reveals a major impact on psychiatric disorder risk 97%
- The impact of rare protein coding genetic variation on adult cognitive function 96%
- Genome-wide analysis of binge-eating disorder identifies the first three risk loci and implicates iron metabolism 96%
Similar papers in this journal
- Transcriptome and chromatin accessibility landscapes across 25 distinct human brain regions expand the susceptibility gene set for neuropsychiatric disorders 96%
- Whole Genome Sequencing Analysis Of Body Mass Index Identifies Novel African Ancestry-Specific Risk Allele 96%
- Genetic correlates of evolutionary adaptations in cognitive functional brain networks and their relationship to human cognitive functioning and disease 96%
Similar papers in this journal
- Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes 96%
- Variant-resolved prediction of context-specific isoform variation with a graph-based attention model 95%
- Meta-analysis fine-mapping is often miscalibrated at single-variant resolution 95%
"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.