Neuropeptide Y receptor genes are associated with alcohol dependence, alcohol withdrawal phenotypes, and cocaine dependence
Open accessAbstract
Background: Several lines of evidence in both human and animal studies suggest that variation in neuropeptide Y (NPY) or its receptor genes (NPY1R, NPY2R and NPY5R) is associated with alcohol dependence as well as alcohol withdrawal symptoms. Additional studies suggest that cocaine may affect NPY expression. Methods: A total of 39 single nucleotide polymorphisms (SNPs) were genotyped across NPY and its 3 receptor genes in a sample of 1,923 subjects from 219 multiplex alcoholic families of European American descent recruited as part of the Collaborative Studies on the Genetics of Alcoholism (COGA) study. Family‐based association analysis was performed to test the primary hypothesis that variation in these genes is associated with alcohol dependence. Secondary analyses evaluated whether there was an association of these SNPs with symptoms of alcohol withdrawal, cocaine dependence, or comorbid alcohol and cocaine dependence. Results: Although variations in NPY itself were not associated with these phenotypes, variations in 2 NPY‐receptor genes were. SNPs in NPY2R provided significant evidence of association with alcohol dependence, alcohol withdrawal symptoms, comorbid alcohol and cocaine dependence, and cocaine dependence (all p < 0.03). Haplotype analyses strengthened the evidence for these phenotypes (global 0.0004 < p < 0.005). SNPs in NPY5R demonstrated significant association with alcohol withdrawal characterized by seizures (p < 0.05). Conclusion: These results indicate that sequence variations in NPY receptor genes are associated with alcohol dependence, particularly a severe subtype of alcohol dependence characterized by withdrawal symptoms, comorbid alcohol and cocaine dependence, and cocaine dependence.
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NPY2R gene SNPs are associated with alcohol dependence, alcohol withdrawal symptoms, tobacco addiction, comorbid alcohol and cocaine dependence, and cocaine dependence.
“Associations were found between SNPs of the NPY Y2 receptor (NPY2R) gene and alcohol dependence, alcohol withdrawal symptoms, tobacco addiction, comorbid alcohol and cocaine dependence, and cocaine dependence (Wetherill et al., 2008;Okahisa et al., 2009;Mutschler et al., 2012;Bhaskar et al., 2013).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Wetherill et al., 2008
The Abstract Results and Results > Association results report NPY2R SNP associations with alcohol dependence, withdrawal symptoms, comorbid alcohol and cocaine dependence, and cocaine dependence. The paper does not report an NPY2R association with tobacco addiction; that part of the sentence is not supported by this source. (LLM, conf=0.91)
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- Authors
- Wetherill, L., Schuckit, M. A., Hesselbrock, V., Xuei, X., Liang, T., Dick, D. M., Kramer, J., Nurnberger Jr., J. I., Tischfield, J. A., Porjesz, B., Edenberg, H. J., & Foroud, T.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Foroud, Tatiana
- ORCID
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2008-12
- Volume
- 32
- Issue
- 12
- Pages
- 2031-2040
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- PMC
- PMC2650441
- OpenAlex
- W2156322627
- Cited by
- 83
- References
- 107
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 6 · 2019: 1 · 2018: 6 · 2017: 5 · 2016: 4 · 2015: 10 · 2014: 4 · 2013: 8 · 2012: 11
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA010707, U10AA008401)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- neuropeptide Y, NPY2R, alcoholism, alcohol withdrawal, cocaine dependence, single nucleotide polymorphisms, haplotype analysis, alcohol withdrawal seizures, genetic association
- MeSH terms
- Alcoholism, Gene Frequency, Humans, Phenotype, Substance Withdrawal Syndrome, Genetic Variation, Receptors, Neuropeptide Y, Cocaine-Related Disorders, Polymorphism, Single Nucleotide
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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