A functional neuropeptide Y Leu7Pro polymorphism associated with alcohol dependence in a large population sample from the United States.
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- Authors
- Lappalainen, Jaakko; Kranzler, Henry R; Malison, Robert; Price, Lawrence H; Van Dyck, Christopher; Rosenheck, Robert A; Cramer, Joyce; Southwick, Steven; Charney, Dennis; Krystal, John; Gelernter, Joel
- Year
- 2002
- Journal
- Archives of general psychiatry
- PMID
- 12215082
- DOI
- 10.1001/archpsyc.59.9.825
BACKGROUND: Quantitative trait locus studies, and observations in animals manipulated for the neuropeptide Y (NPY) gene suggest that variation within this gene may contribute to alcoholism. A recent population study suggested that the Pro7 allele of a functional NPY polymorphism (Leu7Pro) may be associated with increased alcohol consumption. We tested whether the Pro7 allele is associated with alcohol dependence in European Americans (EA). METHODS: The design was a population study comparing the Leu7Pro allele frequencies in alcohol-dependent subjects and controls. Population stratification potential and diagnostic specificity was studied by genotyping individuals from additional populations and psychiatric diagnostic classes. We studied 2 independently collected samples of EA alcohol-dependent subjects (sample 1, n = 307; sample 2, n = 160) and a sample of psychiatrically screened EA controls (n = 202); 8 population samples, including African Americans and European Americans (total n = 551); and 4 samples of individuals with Alzheimer disease, schizophrenia, posttraumatic stress disorder, and major depression (total n = 502). The main outcome measure was the difference in Leu7Pro allele frequencies between alcohol-dependent subjects and controls. RESULTS: The frequency of the Pro7 allele was higher in the alcohol-dependent subjects (sample 1, 5.5%; sample 2, 5.0%) compared with the screened EA controls (2.0%) (sample 1 vs controls, P=.006; sample 2 vs controls, P=.03). The attributable fraction (excess morbidity) in similarly affected populations, owing to the Pro7 allele, was estimated to be 7.3%. The frequency of the Pro7 allele was equal or lower in the population samples, as compared with the screened EA controls (0%-2.2%), with 1 exception (Bedouins). We found no significant evidence that the association of the Pro7 allele with alcohol dependence was due to an association with a comorbid psychiatric disorder. CONCLUSIONS: These results suggest that the NPY Pro7 allele is a risk factor for alcohol dependence. This is only the second specific genetic mechanism ever identified that modulates risk for alcohol dependence.
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| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Correlation between <i>5-HTTLPR</i> gene polymorphism and cognitive function of traumatic stress in Chinese Han children. | Wu M et al. | β | 2022 | β |
| Meta-Analysis on the Association of Neuropeptide Y rs16139 Variant With the Risk of Alcoholism. | Chen B et al. | β | 2021 | β |
| Neuropeptide Y as a risk factor for cardiorenal disease and cognitive dysfunction in chronic kidney disease: translational opportunities and challenges. | Zoccali C et al. | β | 2021 | β |
| Flying Together: <i>Drosophila</i> as a Tool to Understand the Genetics of Human Alcoholism. | Lathen DR et al. | β | 2020 | β |
| Selected neuropeptide genes show genetic differentiation between Africans and non-Africans. | Tai KY et al. | β | 2020 | β |
| Essential Role of Histone Methyltransferase G9a in Rapid Tolerance to the Anxiolytic Effects of Ethanol. | Berkel TDM et al. | β | 2019 | β |
| A Critical Review of Methods and Results in the Search for Genetic Contributors to Alcohol Sensitivity. | Schuckit MA | β | 2018 | β |
| Biological underpinnings of an internalizing pathway to alcohol, cigarette, and marijuana use. | Trucco EM et al. | β | 2018 | β |
| Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain Reward and Stress Systems. | Yeung EW et al. | β | 2017 | β |
| The Role of Neuropeptide Y (NPY) in Alcohol and Drug Abuse Disorders. | Robinson SL et al. | β | 2017 | β |
| Genome-wide significant loci for addiction and anxiety. | Hodgson K et al. | β | 2016 | β |
| Common single nucleotide variants underlying drug addiction: more than a decade of research. | BΓΌhler KM et al. | β | 2015 | β |
| Drosophila and Caenorhabditis elegans as Discovery Platforms for Genes Involved in Human Alcohol Use Disorder. | Grotewiel M et al. | β | 2015 | β |
| A molecular prospective provides new insights into implication of PDYN and OPRK1 genes in alcohol dependence. | Faisal M et al. | β | 2014 | β |
| Genetic approaches to understanding post-traumatic stress disorder. | Almli LM et al. | β | 2014 | β |
| Genetics of alcohol dependence: a review of clinical studies. | Samochowiec J et al. | β | 2014 | β |
| Genome-wide exploration identifies sex-specific genetic effects of alleles upstream NPY to increase the risk of severe periodontitis in men. | Freitag-Wolf S et al. | β | 2014 | β |
| Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders. | Vadnie CA et al. | β | 2014 | β |
| Neurobehavioral Mechanisms of Traumatic Stress in Post-traumatic Stress Disorder. | Lapiz-Bluhm MD et al. | β | 2014 | β |
| Progress towards understanding the genetics of posttraumatic stress disorder. | Voisey J et al. | β | 2014 | β |
| PTSD risk associated with a functional DRD2 polymorphism in heroin-dependent cases and controls is limited to amphetamine-dependent individuals. | Nelson EC et al. | β | 2014 | β |
| A single-nucleotide polymorphism of human neuropeptide s gene originated from Europe shows decreased bioactivity. | Deng C et al. | β | 2013 | β |
| Association between neuropeptide Y gene polymorphisms and alcohol dependence: a case-control study in two independent populations. | Bhaskar LV et al. | β | 2013 | β |
| Genetically selected alcohol preferring rats to model human alcoholism. | Ciccocioppo R | β | 2013 | β |
| NOS1AP is associated with increased severity of PTSD and depression in untreated combat veterans. | Lawford BR et al. | β | 2013 | β |
| Polymorphisms of genes in neurotransmitter systems were associated with alcohol use disorders in a Tibetan population. | Xu Y et al. | β | 2013 | β |
| A DRD2 and ANKK1 haplotype is associated with nicotine dependence. | Voisey J et al. | β | 2012 | β |
| Alcohol Dependence and Genes Encoding Ξ±2 and Ξ³1 GABAA Receptor Subunits: Insights from Humans and Mice. | Borghese CM et al. | β | 2012 | β |
| Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression. | Koefoed P et al. | β | 2012 | β |
| Genetic Association of NPY Gene Polymorphisms with Dampness-Phlegm Pattern in Korean Stroke Patients. | Ko MM et al. | β | 2012 | β |
| Genetic modulation of plasma NPY stress response is suppressed in substance abuse: association with clinical outcomes. | Xu K et al. | β | 2012 | β |
| Neurobiology of consummatory behavior: mechanisms underlying overeating and drug use. | Barson JR et al. | β | 2012 | β |
| PTSD and gene variants: new pathways and new thinking. | Skelton K et al. | β | 2012 | β |
| Acupuncture for posttraumatic stress disorder: conceptual, clinical, and biological data support further research. | Hollifield M | β | 2011 | β |
| Genomewide association analysis of symptoms of alcohol dependence in the molecular genetics of schizophrenia (MGS2) control sample. | Kendler KS et al. | β | 2011 | β |
| Impact of early life stress on alcohol consumption and on the short- and long-term responses to alcohol in adolescent female rats. | Van Waes V et al. | β | 2011 | β |
| No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders. | Kindler J et al. | β | 2011 | β |
| Association between neuropeptide Y receptor 2 polymorphism and the smoking behavior of elderly Japanese. | Sato N et al. | β | 2010 | β |
| Candidate genes for alcohol preference identified by expression profiling in alcohol-preferring and -nonpreferring reciprocal congenic rats. | Liang T et al. | β | 2010 | β |
| Circadian clock gene polymorphisms in alcohol use disorders and alcohol consumption. | Kovanen L et al. | β | 2010 | β |
| Functional NPY variation as a factor in stress resilience and alcohol consumption in rhesus macaques. | Lindell SG et al. | β | 2010 | β |
| Genetics of post-traumatic stress disorder: review and recommendations for genome-wide association studies. | Cornelis MC et al. | β | 2010 | β |
| Identification of genes influencing skeletal phenotypes in congenic P/NP rats. | Alam I et al. | β | 2010 | β |
| Neuropeptide Y signaling in the central nucleus of amygdala regulates alcohol-drinking and anxiety-like behaviors of alcohol-preferring rats. | Zhang H et al. | β | 2010 | β |
| NPY moderates the relation between hurricane exposure and generalized anxiety disorder in an epidemiologic sample of hurricane-exposed adults. | Amstadter AB et al. | β | 2010 | β |
| Psychogenetics of post-traumatic stress disorder: a short review. | Rady A et al. | β | 2010 | β |
| Therapeutic potential of neuropeptide Y (NPY) receptor ligands. | Brothers SP et al. | β | 2010 | β |
| Association between neuropeptide Y gene and its receptor Y1 gene and methamphetamine dependence. | Okahisa Y et al. | β | 2009 | β |
| From QTL to candidate gene: a genetic approach to alcoholism research. | Spence JP et al. | β | 2009 | β |
| Genetics of PTSD: Fear Conditioning as a Model for Future Research. | Amstadter AB et al. | β | 2009 | β |
| PreproNPY Pro7 protects against depression despite exposure to environmental risk factors. | SjΓΆholm LK et al. | β | 2009 | β |
| The DRD2 gene 957C>T polymorphism is associated with posttraumatic stress disorder in war veterans. | Voisey J et al. | β | 2009 | β |
| The effect of endogenous preproneuropeptide Y leucine 7 to proline 7 polymorphism on growth and apoptosis in primary cultured HUVECs. | Kaipio K et al. | β | 2009 | β |
| The efficacies of clozapine and haloperidol in refractory schizophrenia are related to DTNBP1 variation. | Zuo L et al. | β | 2009 | β |
| The intracellular mobility of NPY and a putative mitochondrial form of NPY in neuronal cells. | Kaipio K et al. | β | 2009 | β |
| Analysis of single nucleotide polymorphisms and haplotypes in the neuropeptide Y gene: no evidence for association with alcoholism in a German population sample. | Zill P et al. | β | 2008 | β |
| Approach to the genetics of alcoholism: a review based on pathophysiology. | KΓΆhnke MD | β | 2008 | β |
| Gene-environment interaction in posttraumatic stress disorder: review, strategy and new directions for future research. | Koenen KC et al. | β | 2008 | β |
| Genetics of post-traumatic stress disorder: informing clinical conceptualizations and promoting future research. | Nugent NR et al. | β | 2008 | β |
| Molecular genetics of the stress-responsive adrenocortical axis. | Redei EE | β | 2008 | β |
| Neurobiology of addiction. An integrative review. | Goodman A | β | 2008 | β |
| Neuropeptide Y receptor genes are associated with alcohol dependence, alcohol withdrawal phenotypes, and cocaine dependence. | Wetherill L et al. | β | 2008 | β |
| Allelic variation in the NPY gene in 14 Indian populations. | Bhaskar LVKS et al. | β | 2007 | β |
| Emerging approaches to managing alcohol dependence. | Swift R | β | 2007 | β |
| Genetic and environmental factors in complex neurodevelopmental disorders. | van Loo KM et al. | β | 2007 | β |
| Genetics of posttraumatic stress disorder: Review and recommendations for future studies. | Koenen KC et al. | β | 2007 | β |
| Pharmacogenetic aspects of addictive behaviors. | Hejazi NS | β | 2007 | β |
| Potential genetic variants in schizophrenia: a Bayesian analysis. | Hall H et al. | β | 2007 | β |
| Stress, NPY and vascular remodeling: Implications for stress-related diseases. | Kuo LE et al. | β | 2007 | β |
| The genetic background to PTSD. | Broekman BF et al. | β | 2007 | β |
| A guide to the genetics of psychiatric disease. | Hough CJ et al. | β | 2006 | β |
| A rational approach to the pharmacotherapy of alcohol dependence. | Petrakis IL | β | 2006 | β |
| Human NPY gene variants in cardiovascular and metabolic diseases. | Pesonen U | β | 2006 | β |
| New findings on the genetic influences on alcohol use and dependence. | Higuchi S et al. | β | 2006 | β |
| The alcohol-preferring P rat and animal models of excessive alcohol drinking. | Bell RL et al. | β | 2006 | β |
| An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk. | Hu X et al. | β | 2005 | β |
| A novel single nucleotide polymorphism of the neuropeptide Y (NPY) gene associated with alcohol dependence. | Mottagui-Tabar S et al. | β | 2005 | β |
| Association between alcoholism and gamma-amino butyric acid alpha2 receptor subtype in a Russian population. | Lappalainen J et al. | β | 2005 | β |
| Categorical and continuous models of liability to externalizing disorders: a direct comparison in NESARC. | Markon KE et al. | β | 2005 | β |
| [DNA polymorphisms and alcoholism]. | Pastor I et al. | β | 2005 | β |
| Effect of polymorphism on expression of the neuropeptide Y gene in inbred alcohol-preferring and -nonpreferring rats. | Spence JP et al. | β | 2005 | β |
| Increased fasting plasma ghrelin levels during alcohol abstinence. | Kim DJ et al. | β | 2005 | β |
| Practical population group assignment with selected informative markers: characteristics and properties of Bayesian clustering via STRUCTURE. | Yang BZ et al. | β | 2005 | β |
| The genetics of addictions: uncovering the genes. | Goldman D et al. | β | 2005 | β |
| The T1128C polymorphism of neuropeptide Y gene in a chinese population. | Jia C et al. | β | 2005 | β |
| A cluster of differentially expressed signal transduction genes identified by microarray analysis in a rat genetic model of alcoholism. | Arlinde C et al. | β | 2004 | β |
| Alcoholism: genes and mechanisms. | Oroszi G et al. | β | 2004 | β |
| Allelic and haplotypic association of GABRA2 with alcohol dependence. | Covault J et al. | β | 2004 | β |
| A role for neuropeptide Y in neurobiological responses to ethanol and drugs of abuse. | Thiele TE et al. | β | 2004 | β |
| Assessment of ethanol consumption and water drinking by NPY Y(2) receptor knockout mice. | Thiele TE et al. | β | 2004 | β |
| Confirmation and fine mapping of the chromosome 1 alcohol dependence risk locus. | Lappalainen J et al. | β | 2004 | β |
| Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism. | Heilig M et al. | β | 2004 | β |
| Functional genomics strategies to identify susceptibility genes and treatment targets in alcohol dependence. | Heilig M et al. | β | 2004 | β |
| Genes associated with addiction: alcoholism, opiate, and cocaine addiction. | Kreek MJ et al. | β | 2004 | β |
| Genomic regions controlling corticosterone levels in rats. | Potenza MN et al. | β | 2004 | β |
| Innate differences in neuropeptide Y (NPY) mRNA expression in discrete brain regions between alcohol-preferring (P) and -nonpreferring (NP) rats: a significantly low level of NPY mRNA in dentate gyrus of the hippocampus and absence of NPY mRNA in the medial habenular nucleus of P rats. | Hwang BH et al. | β | 2004 | β |
| Natural variation in the npr-1 gene modifies ethanol responses of wild strains of C. elegans. | Davies AG et al. | β | 2004 | β |
| Neuropeptide Y and Y2-receptor are involved in development of diabetic retinopathy and retinal neovascularization. | Koulu M et al. | β | 2004 | β |
| NOTCH4 gene haplotype is associated with schizophrenia in African Americans. | Luo X et al. | β | 2004 | β |
| Pharmacogenetic studies of alcohol self-administration and withdrawal. | Crabbe JC et al. | β | 2004 | β |
| Stress and alcohol drinking. | Sillaber I et al. | β | 2004 | β |
| Alcoholism and obesity: overlapping neuropeptide pathways? | Thiele TE et al. | β | 2003 | β |
| A role for neuropeptide Y in alcohol intake control: evidence from human and animal research. | Thiele TE et al. | β | 2003 | β |
| Association between a novel polymorphism in the promoter region of the neuropeptide Y gene and schizophrenia in humans. | Itokawa M et al. | β | 2003 | β |
| Candidate genes for alcohol dependence: a review of genetic evidence from human studies. | Dick DM et al. | β | 2003 | β |
| Drug addiction. | CamΓ J et al. | β | 2003 | β |
| [Low prevalence of the Leu7/Pro polymorphism in the signal peptide of preproneuropeptide Y in the Spanish Mediterranean population]. | PortolΓ©s O et al. | β | 2003 | β |
| Neuropeptide gene polymorphisms and human behavioural disorders. | Inui A | β | 2003 | β |
| NPY Leu7Pro and alcohol dependence in Finnish and Swedish populations. | Zhu G et al. | β | 2003 | β |
| Peptides: their role in excess alcohol drinking and their promise as a therapeutic tool. | Egli M | β | 2003 | β |
| Pharmacogenomics of alcohol response and addiction. | Enoch MA | β | 2003 | β |