Phenotypic heterogeneity in study populations may significantly confound the results of genetic association studies on alcohol dependence.
- Authors
- Ali, M Adam; Way, Michael J; Marks, Michael; Guerrini, Irene; Thomson, Allan D; Strang, John; McQuillin, Andrew; Morgan, Marsha Y
- Year
- 2015
- Journal
- Psychiatric genetics
- PMID
- 26368818
- DOI
- 10.1097/YPG.0000000000000105
BACKGROUND: The interpretation of genetic studies on alcohol dependence may be confounded by the co-occurrence of substance dependence, psychiatric disorders and alcohol-related comorbidities, for example, cirrhosis. Significant single-marker and haplotypic associations between polymorphisms in the zinc finger gene, ZNF699, and alcohol dependence were reported in the Irish Affected Sib Pair Study of Alcohol Dependence population, one-third of whom had co-occurring substance dependence while 80% had identified psychiatric comorbidity. The aim of this study was to explore variant ZNF699 associations with alcohol dependence while exercising controls for potential confounders. METHODS: The study population was comprised of 1449 alcohol-dependent cases and 1283 population controls; all were of British or Irish ancestry. None of the cases had a history of dependence on other substances, and the frequency of comorbid depression was low. A separate, ancestry-matched cohort of 196 opioid-dependent cases was also included. Genotyping for the four previously identified SNPs of interest in ZNF699 was performed using K-Biosciences Competitive Allele Specific PCR. RESULTS: No single-marker associations were found between polymorphisms in ZNF699 and alcohol dependence per se. A significant allelic association was found between rs7254880 in ZNF699 and alcohol-related cirrhosis (n=292), using cases with no biopsy evidence of liver disease (n=314) as controls (P=0.013). Significant allelic associations were also found between rs12460279 (P=0.028), rs7252865 (P=0.012) and rs10854142 (P=0.016) in ZNF699 and opioid dependence. CONCLUSION: Phenotypic variation in study populations may contribute towards the nonreplication of genetic association studies on alcohol dependence; controls for recognised confounding variables should be exercised whenever possible.
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across Population-Based and Clinically Ascertained Samples. | 2018 | 29405378 |
External
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|---|---|---|---|---|
| Clinical and ocular abnormalities in DEGCAGS syndrome-Developmental delay with gastrointestinal, cardiovascular, genitourinary, and skeletal abnormalities. | Ali SM et al. | — | 2024 | → |
| Epigenomic and phenotypic characterization of DEGCAGS syndrome. | Karimi K et al. | — | 2024 | → |
| Further Delineation of Developmental Delay with Gastrointestinal, Cardiovascular, Genitourinary, and Skeletal Abnormalities Caused by <i>ZNF699</i> Gene Mutation. | Biela M et al. | — | 2022 | → |
| The influence of regression models on genome-wide association studies of alcohol dependence: a comparison of binary and quantitative analyses. | Li W et al. | — | 2021 | → |
| Associations between alcohol dehydrogenase genes and alcohol use across early and middle adolescence: Moderation × Preventive intervention. | Cleveland HH et al. | — | 2018 | → |
| Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across Population-Based and Clinically Ascertained Samples. | Savage JE et al. | — | 2018 | → |
| The genetics of alcohol dependence and alcohol-related liver disease. | Stickel F et al. | — | 2017 | → |