The etiology of DSM-5 alcohol use disorder: Evidence of shared and non-shared additive genetic effects.
- Authors
- Palmer, Rohan H C; Brick, Leslie A; Chou, Yi-Ling; Agrawal, Arpana; McGeary, John E; Heath, Andrew C; Bierut, Laura; Keller, Matthew C; Johnson, Eric; Hartz, Sarah M; Schuckit, Marc A; Knopik, Valerie S
- Year
- 2019
- Journal
- Drug and alcohol dependence
- PMID
- 31229702
- DOI
- 10.1016/j.drugalcdep.2018.12.034
- PMCID
- PMC6929687
BACKGROUND: Alcoholism is a multifactorial disorder influenced by multiple gene loci, each with small effect. Studies suggest shared genetic influences across DSM-IV alcohol dependence symptoms, but shared effects across DSM-5 alcohol use disorder remains unknown. We aimed to test the assumption of genetic homogeneity across the 11 criteria of DSM-5 alcohol use disorder (AUD). 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 (rGSNP) between 11 DSM-5 AUD symptoms. Phenotypic relationships between symptoms were examined to confirm an underlying liability of AUD and the SNP-heritability of the observed latent trait and the co-heritabilityamong AUD symptoms was assessed using Genomic-Relatedness-Matrix-Restricted-Maximum-Likelihood. Genetic covariance among symptoms was examined using factor analysis. RESULTS: Phenotypic relationships confirmed a unidimensional underlying liability to AUD. Factor and parallel analyses of the observed genetic variance/covariance provided evidence of genetic homogeneity. Additive genetic effects on DSM-5 AUD symptoms varied from 0.10 to 0.37 and largely overlapped (rG-SNP across symptoms ranged from 0.49 - 0.92). The additive genetic effect on the DSM-5 AUD factor was 0.36, 0.14 for DSM-5 AUD diagnosis, and was 0.22 for DSM-5 AUD severity. CONCLUSIONS: Common genetic variants influence DSM-5 AUD symptoms. Despite evidence for a common AUD factor, the evidence of only partially overlapping genetic effects across AUD symptoms further substantiates the need to simultaneously model common and symptom-specific genetic effects in molecular genetic studies in order to best characterize the genetic liability.
Parallel analysis of 11×11 genetic covariance matrix for DSM-5 AUD symptomsObserved eigenvalues (solid line) are compared to 95 percentile of the eigenvalue distribution (dashed line [with standard error]) derived from 1000 randomly generated datasets. All factors left of where the solid lines first intersects with the dashed line are retained and their effects described in Table 4.
LLM interpretation
This line graph shows a parallel analysis of an 11×11 genetic covariance matrix for DSM-5 AUD symptoms, plotting eigenvalues against factor numbers. The observed eigenvalues (solid line) start significantly higher than the simulated mean (dashed line with error bars) for the first factor, but drop below the simulated values starting at factor 2. The x-axis represents the factor number (1.00 to 11.00) and the y-axis represents the eigenvalue (-0.2 to 0.5).
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