Using a gene-set-based analysis of GWAS data from individuals identified as alcohol dependent vs. controls, the most frequently identified gene in the significantly associated genes-sets was XRCC5 (X-Ray Repair Cross Complementing 5). XRCC5 encodes an ATP-dependent DNA helicase that functions in the repair of DNA double-strand breaks. There is a single orthologous gene in Drosophila, Ku80, for which RNAi-targeting constructs have been generated.
The human XRCC5 gene has not been introduced into flies.
In Drosophila, pan-neuronal expression of an RNAi construct targeting Ku80 results in reduced sensitivity to ethanol. Physical interactions of Dmel\Ku80 have been described; see below and in the Ku80 gene report.
[updated Jan. 2018 by FlyBase; FBrf0222196]
Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).
The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)
Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).
Alcoholism is a multifactorial, genetically influenced disorder. [from MIM:103780; 2017.12.19]
XRCC5 encodes an ATP-dependent DNA helicase that functions in the repair of DNA double-strand breaks; functions as a dimer with XRCC6. [Gene Cards, XRCC5, 2018.01.17]
One to one (1 human to 1 Drosophila).
High-scoring ortholog of human XRCC5 (1 Drosophila to 1 human). Dmel\Ku80 shares 22% identity and 41% similarity with the human gene.
