The genetics of alcohol dependence: Twin and SNP‐based heritability, and genome‐wide association study based on AUDIT scores
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Alcohol dependence (AD) is among the most common and costly public health problems contributing to morbidity and mortality throughout the world. In this study, we investigate the genetic basis of AD in a Dutch population using data from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA). The presence of AD was ascertained via the Alcohol Use Disorders Identification Test (AUDIT) applying cut‐offs with good specificity and sensitivity in identifying those at risk for AD. Twin‐based heritability of AD‐AUDIT was estimated using structural equation modeling of data in 7,694 MZ and DZ twin pairs. Variance in AD‐AUDIT explained by all SNPs was estimated with genome‐wide complex trait analysis (GCTA). A genome‐wide association study (GWAS) was performed in 7,842 subjects. GWAS SNP effect concordance analysis was performed between our GWAS and a recent AD GWAS using DSM‐IV diagnosis. The twin‐based heritability of AD‐AUDIT was estimated at 60% (55–69%). GCTA showed that common SNPs jointly capture 33% (SE = 0.12, P = 0.002) of this heritability. In the GWAS, the top hits were positioned within four regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019 (P = 7.58 × 10−7). This first GWAS of AD using the AUDIT measure found results consistent with previous genetic studies using DSM diagnosis: concordance in heritability estimates and direction of SNPs effect and overlap with top hits from previous GWAS. Thus, the use of appropriate questionnaires may represent cost‐effective strategies to phenotype samples in large‐scale biobanks or other population‐based datasets. © 2015 Wiley Periodicals, Inc.
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This distinction appears to be the case in studies that used specific cut-offs to harmonize AUDIT scores with AD data.
“This appears to be the case in studies that used specific cut-offs to harmonize AUDIT scores with AD data30,34.”
From Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders (2018) · cites this paper as [34]
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- Authors
- Mbarek, H., Milaneschi, Y., Fedko, I. O., Hottenga, J., de Moor, M. H. M., Jansen, R., Gelernter, J., Sherva, R., Willemsen, G., Boomsma, D. I., Penninx, B. W., & Vink, J. M.
- Affiliations
- Vrije Universiteit Amsterdam (NL)
- Amsterdam Public Health (NL)
- Department of Biological Psychology VU University Amsterdam Amsterdam The Netherlands
- Yale University (US)
- Boston University (US)
- Corresponding author
- Mbarek, Hamdi
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2015-09-14
- Volume
- 168
- Issue
- 8
- Pages
- 739-748
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- OpenAlex
- W1936180167
- Cited by
- 66
- References
- 61
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 6 · 2019: 8 · 2018: 14 · 2017: 12 · 2016: 4
- FWCI
- 6.76
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- VU Research Portal (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- European Research Council (ERC‐230374, 284167)
- National Institute of Mental Health (U24 MH068457‐06)
- National Institutes of Health (R01 HD042157‐01A1, MH081802, 1RC2 MH089951, 1RC2 MH089995)
- Netherlands Organisation for Health Research and Development (10‐000‐1002)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- alcoholism, heritability, twin studies, single nucleotide polymorphisms, genome-wide association study, auditing, genetic risk factors, biobanks
- MeSH terms
- Adult, Alcoholism, Female, Humans, Male, Netherlands, Twins, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Genetic Association Studies
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