Neurogenetic and multi-omic sources of overlap among sensation seeking, alcohol consumption, and alcohol use disorder.

Autor: Miller AP; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA., Gizer IR; Department of Psychological Sciences, University of Missouri, Columbia, Missouri, USA.
Jazyk: angličtina
Zdroj: Addiction biology [Addict Biol] 2024 Feb; Vol. 29 (2), pp. e13365.
DOI: 10.1111/adb.13365
Abstrakt: Sensation seeking is bidirectionally associated with levels of alcohol consumption in both adult and adolescent samples, and shared neurobiological and genetic influences may in part explain these associations. Links between sensation seeking and alcohol use disorder (AUD) may primarily manifest via increased alcohol consumption rather than through direct effects on increasing problems and consequences. Here the overlap among sensation seeking, alcohol consumption, and AUD was examined using multivariate modelling approaches for genome-wide association study (GWAS) summary statistics in conjunction with neurobiologically informed analyses at multiple levels of investigation. Meta-analytic and genomic structural equation modelling (GenomicSEM) approaches were used to conduct GWAS of sensation seeking, alcohol consumption, and AUD. Resulting summary statistics were used in downstream analyses to examine shared brain tissue enrichment of heritability and genome-wide evidence of overlap (e.g., stratified GenomicSEM, RRHO, genetic correlations with neuroimaging phenotypes), and to identify genomic regions likely contributing to observed genetic overlap across traits (e.g., H-MAGMA and LAVA). Across approaches, results supported shared neurogenetic architecture between sensation seeking and alcohol consumption characterised by overlapping enrichment of genes expressed in midbrain and striatal tissues and variants associated with increased cortical surface area. Alcohol consumption and AUD evidenced overlap in relation to variants associated with decreased frontocortical thickness. Finally, genetic mediation models provided evidence of alcohol consumption mediating associations between sensation seeking and AUD. This study extends previous research by examining critical sources of neurogenetic and multi-omic overlap among sensation seeking, alcohol consumption, and AUD which may underlie observed phenotypic associations.
(© 2024 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)
Databáze: MEDLINE
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