Novel characterization of the multivariate genetic architecture of internalizing psychopathology and alcohol use

Genetic correlations suggest that the genetic relationship of alcohol use with internalizing psychopathology depends on the measure of alcohol use. Problematic alcohol use (PAU) is positively genetically correlated with internalizing psychopathology, whereas alcohol consumption ranges from not signi...

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Bibliographic Details
Published in:American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2021-09, Vol.186 (6), p.353-366
Main Authors: Colbert, Sarah M. C., Funkhouser, Scott A., Johnson, Emma C., Morrison, Claire L., Hoeffer, Charles A., Friedman, Naomi P., Ehringer, Marissa A., Evans, Luke M.
Format: Article
Language:English
Subjects:
Alcohol Drinking - genetics
Alcohol use
Alcoholism - genetics
Genetic relationship
genetic risk
Genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Humans
internalizing psychopathology
Multivariate analysis
problematic alcohol use
Psychopathology
substance use
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Summary:Genetic correlations suggest that the genetic relationship of alcohol use with internalizing psychopathology depends on the measure of alcohol use. Problematic alcohol use (PAU) is positively genetically correlated with internalizing psychopathology, whereas alcohol consumption ranges from not significantly correlated to moderately negatively correlated with internalizing psychopathology. To explore these different genetic relationships of internalizing psychopathology with alcohol use, we performed a multivariate genome‐wide association study of four correlated factors (internalizing psychopathology, PAU, quantity of alcohol consumption, and frequency of alcohol consumption) and then assessed genome‐wide and local genetic covariance between these factors. We identified 14 significant regions of local, largely positive, genetic covariance between PAU and internalizing psychopathology and 12 regions of significant local genetic covariance (including both positive and negative genetic covariance) between consumption factors and internalizing psychopathology. Partitioned genetic covariance among functional annotations suggested that brain tissues contribute significantly to positive genetic covariance between internalizing psychopathology and PAU but not to the genetic covariance between internalizing psychopathology and quantity or frequency of alcohol consumption. We hypothesize that genome‐wide genetic correlations between alcohol use and psychiatric traits may not capture the more complex shared or divergent genetic architectures at the locus or tissue specific level. This study highlights the complexity of genetic architectures of alcohol use and internalizing psychopathology, and the differing shared genetics of internalizing disorders with PAU compared to consumption.
ISSN:1552-4841
1552-485X
DOI:10.1002/ajmg.b.32874