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Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across Population-Based and Clinically Ascertained Samples
- Source :
- Alcoholism, clinical and experimental research. 42(3)
- Publication Year :
- 2017
-
Abstract
- BACKGROUND: Despite consistent evidence of the heritability of alcohol use disorders (AUDs), few specific genes with an etiological role have been identified. It is likely that AUDs are highly polygenic; however, the etiological pathways and genetic variants involved may differ between populations. The aim of this study was thus to evaluate whether aggregate genetic risk for AUDs differed between clinically ascertained and population-based epidemiological samples. METHODS: Four independent samples were obtained: 2 from unselected birth cohorts (Avon Longitudinal Study of Parents and Children [ALSPAC], N = 4,304; FinnTwin12 [FT12], N = 1,135) and 2 from families densely affected with AUDs, identified from treatment-seeking patients (Collaborative Study on the Genetics of Alcoholism, N = 2,097; Irish Affected Sib Pair Study of Alcohol Dependence, N = 706). AUD symptoms were assessed with clinical interviews, and participants of European ancestry were genotyped. Genomewide association was conducted separately in each sample, and the resulting association weights were used to create polygenic risk scores in each of the other samples (12 total discovery-validation pairs), and from meta-analyses within sample type. We then tested how well these aggregate genetic scores predicted AUD outcomes within and across sample types. RESULTS: Polygenic scores derived from 1 population-based sample (ALSPAC) significantly predicted AUD symptoms in another population-based sample (FT12), but not in either clinically ascertained sample. Trend-level associations (uncorrected p
- Subjects :
- 0301 basic medicine
Adult
Male
Risk
medicine.medical_specialty
Longitudinal study
Multifactorial Inheritance
Adolescent
Population
Medicine (miscellaneous)
Genome-wide association study
Sample (statistics)
Toxicology
Risk Assessment
White People
Article
03 medical and health sciences
Young Adult
Epidemiology
mental disorders
Medicine
Humans
education
education.field_of_study
business.industry
Genetic heterogeneity
Alcohol dependence
Heritability
3. Good health
Psychiatry and Mental health
Alcoholism
030104 developmental biology
Female
business
Demography
Subjects
Details
- ISSN :
- 15300277
- Volume :
- 42
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Alcoholism, clinical and experimental research
- Accession number :
- edsair.doi.dedup.....0e85db5aa78d14be4d6d22bbc780136e