Purpose: GWAS on alcoholism are challenged by the fact that it is a multifactorial disorder influenced by multiple interacting genes, each with small effect. Recent studies (Kendler, Aggen, Prescott, Crabbe, & Neale, 2012;... [ view full abstract ]
Purpose: GWAS on alcoholism are challenged by the fact that it is a multifactorial disorder influenced by multiple interacting genes, each with small effect. Recent studies (Kendler, Aggen, Prescott, Crabbe, & Neale, 2012; Palmer et al., 2015) suggest shared genetic influences across DSM-IV alcohol dependence (AD) symptoms, but these have been limited to DSM-IV criteria. We recently showed (Palmer et al., 2015) largely overlapping additive genetic effects using common autosomal markers providing support for the assumption of genetic homogeneity for DSM-IV indicators. The present study examined these same hypotheses in the recently expanded definition of DSM-5 alcohol use disorder (AUD) that incorporates new and additional domains of the disease once thought to be indicative of separate disorders.
Methods: Data from 2596 alcohol using individuals of European ancestry from the Study of Addiction: Genetics and Environment were used to examine the genomewide SNP-heritability (h2SNP) and SNP-covariance (rG-SNP) between 11 DSM-5 AUD criteria. Phenotypic relationships between criteria were also examined to confirm an underlying liability of AUD. Likewise, parallel analysis of the observed genetic variance/covariance provided evidence of genetic homogeneity.
Results: Additive genetic effects on DSM-5 AUD criteria vary from mild (0.10) to moderate (0.37) and largely overlap (rG-SNP range from 0.49 – 0.92). Additive genetic influences on the DSM-5 AUD factor was (0.36) and 0.23 on DSM-5 AUD symptom count (0.23).
Conclusion: Common genetic variants influence DSM-5 AUD criteria. Despite evidence for a common AUD factor, the evidence of only partially overlapping genetic effects across AUD criteria further substantiates the need to simultaneously model common and specific genetic effects across AUD criteria in molecular genetic studies of AUD in order to best index the underlying biology.
