Journal
ADDICTION BIOLOGY
Volume 19, Issue 4, Pages 708-721Publisher
WILEY-BLACKWELL
DOI: 10.1111/adb.12035
Keywords
Clinical validity; genetic risk prediction; polygenic risk score; psychiatric genetic counseling; receiver operating characteristic curve analysis
Categories
Funding
- NIH, National Institute on Alcohol Abuse and Alcoholism (NIAAA) [U10AA008401]
- National Institute on Drug Abuse (NIDA)
- NIAAA, National Institutes of Health, Bethesda, MD, USA [U10 AA008401]
- NIH GEI
- NIH [HHSN268200782096C]
- National Human Genome Research Institute
- National Human Genome Research Institute, Bethesda, MD, USA [U01 HG004422]
- National Institute on Alcohol Abuse and Alcoholism [U10 AA008401]
- National Cancer Institute, Bethesda, MD, USA [P01 CA089392]
- National Institute on Drug Abuse, Bethesda, MD, USA [R01 DA013423, R01 DA019963]
- [K02AA018755]
- [U01HG004438]
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Family-based and genome-wide association studies (GWAS) of alcohol dependence (AD) have reported numerous associated variants. The clinical validity of these variants for predicting AD compared with family history information has not been reported. Using the Collaborative Study on the Genetics of Alcoholism (COGA) and the Study of Addiction: Genes and Environment (SAGE) GWAS samples, we examined the aggregate impact of multiple single nucleotide polymorphisms (SNPs) on risk prediction. We created genetic sum scores by adding risk alleles associated in discovery samples, and then tested the scores for their ability to discriminate between cases and controls in validation samples. Genetic sum scores were assessed separately for SNPs associated with AD in candidate gene studies and SNPs from GWAS analyses that met varying P-value thresholds. Candidate gene sum scores did not exhibit significant predictive accuracy. Family history was a better classifier of case-control status, with a significant area under the receiver operating characteristic curve (AUC) of 0.686 in COGA and 0.614 in SAGE. SNPs that met less stringent P-value thresholds of 0.01-0.50 in GWAS analyses yielded significant AUC estimates, ranging from mean estimates of 0.549 for SNPs with P < 0.01 to 0.565 for SNPs with P < 0.50. This study suggests that SNPs currently have limited clinical utility, but there is potential for enhanced predictive ability with better understanding of the large number of variants that might contribute to risk.
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