• Fernando Facal, Gerardo Flórez, Vanessa Blanco, Julio Rodríguez, César Pereiro, José Manuel Fernández, Emilio Fariñas, Valentín Estévez, Jesús Gómez-Trigo, Xaquín Gurriarán, Pilar Sáiz, Fernando Lino Vázquez, Manuel Arrojo, Javier Costas, and GenPol Study Group.
• Instituto de Investigación Sanitaria (IDIS) de Santiago de Compostela, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Galicia, Spain; Servizo de Psiquiatría, Complexo Hospitalario Universitario de Santiago de Compostela, Servizo Galego de Saúde (SERGAS), Santiago de Compostela, Galicia, Spain; Universidade de Santiago de Compostela (USC), Galicia, Spain.
• Drug Alcohol Depend. 2021 Apr 1; 221: 108556.

BackgroundHigh alcohol consumption and alcohol dependence are only partly genetically correlated and they differ considerably in their correlations with other traits. The existence of genetic correlation among alcohol dependence and psychiatric disorders may be attributed to the presence of a general psychopathology factor, the p factor. This study investigates the relationship of polygenic risk to general psychopathology and to high alcohol consumption on alcohol dependence.MethodsParticipants were 524 alcohol-dependent patients and 729 controls. Polygenic risk scores (PRS) were computed for alcohol consumption (drinks per week) and nine psychiatric disorders. Principal component analysis (PCA) applied to the psychiatric PRS was used to calculate the first principal component as a proxy of the polygenic p factor.ResultsBoth the polygenic p factor and the drinks per week PRS were associated with alcohol dependence in our sample. Both variables are only weakly correlated, contributing additively to the risk for alcohol dependence. Sensitivity analyses showed that the polygenic p factor was also associated with alcohol dependence in the subset of patients without any psychiatric or substance use comorbidity.ConclusionsPolygenic risk for alcohol dependence can be split at least into two components, involved in general psychopathology and high alcohol consumption. The first component of PCA based on PRS for different psychiatric disorders allows estimation of the contribution of the polygenic p factor to alcohol dependence. The pleiotropic effects of genetic variants across psychiatric disorders are mainly manifested as alcohol dependence in some patients.Copyright © 2021 Elsevier B.V. All rights reserved.

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