Neuropeptide Y Receptor Genes Are Associated With Alcohol Dependence, Alcohol Withdrawal Phenotypes, and Cocaine Dependence
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 e...
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| creator | Wetherill, Leah Schuckit, Marc A. Hesselbrock, Victor Xuei, Xiaoling Liang, Tiebing Dick, Danielle M. Kramer, John Nurnberger Jr, John I. Tischfield, Jay A. Porjesz, Bernice Edenberg, Howard J. Foroud, Tatiana |
| description | 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 |
| doi_str_mv | 10.1111/j.1530-0277.2008.00790.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2650441</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20291102</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5710-bd4d24c3af77cf26a72e716f56038f10a799eaa7b9a6de838d4186afe44cba553</originalsourceid><addsrcrecordid>eNqNkU-P0zAQxSMEYsvCV0C-wGkTbOePnQNIUdgtSKtSrUArTtbUmVCXNA52yrbaL78JrcJywxePPL_3ZqwXBITRiA3n3SZiaUxDyoWIOKUyolTkNNo_CWZT42kwoyxJw2zonwUvvN9QShOZZc-DMyYll5KxWXC_wJ2zHXa9qZB8Jzeoh9o6MscWPSkcksJ7qw30WJFb069J0Wi7tg35iB22FbYaL6a3Eagc3EFDlmtsbX_o0F8QaCtSWg2mxUeyl8GzGhqPr073efDt6vJr-Sm8_jL_XBbXoU4Fo-GqSiqe6BhqIXTNMxAcBcvqNKOxrBkFkecIIFY5ZBXKWFYJkxnUmCR6BWkanwcfjr7dbrXFSmPbO2hU58wW3EFZMOrfTmvW6of9rXiW0iRhg8Hbk4Gzv3boe7U1XmPTQIt25xWnPGeM8gGUR1A7673DehrCqBqTUxs1BqTGgNSYnPqTnNoP0tePl_wrPEU1AG9OAHgNTe2g1cZPHKe5ELEYf_v-yN2ZBg__vYAqysuboRr04VFvfI_7SQ_up8rGAep2MVflki_KqzJXy_gBN5rFyw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20291102</pqid></control><display><type>article</type><title>Neuropeptide Y Receptor Genes Are Associated With Alcohol Dependence, Alcohol Withdrawal Phenotypes, and Cocaine Dependence</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><source>Access via Wiley Online Library</source><creator>Wetherill, Leah ; Schuckit, Marc A. ; Hesselbrock, Victor ; Xuei, Xiaoling ; Liang, Tiebing ; Dick, Danielle M. ; Kramer, John ; Nurnberger Jr, John I. ; Tischfield, Jay A. ; Porjesz, Bernice ; Edenberg, Howard J. ; Foroud, Tatiana</creator><creatorcontrib>Wetherill, Leah ; Schuckit, Marc A. ; Hesselbrock, Victor ; Xuei, Xiaoling ; Liang, Tiebing ; Dick, Danielle M. ; Kramer, John ; Nurnberger Jr, John I. ; Tischfield, Jay A. ; Porjesz, Bernice ; Edenberg, Howard J. ; Foroud, Tatiana</creatorcontrib><description>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.</description><identifier>ISSN: 0145-6008</identifier><identifier>EISSN: 1530-0277</identifier><identifier>DOI: 10.1111/j.1530-0277.2008.00790.x</identifier><identifier>PMID: 18828811</identifier><identifier>CODEN: ACRSDM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Addictive behaviors ; Adult and adolescent clinical studies ; Alcoholism ; Alcoholism - complications ; Alcoholism - genetics ; Alcoholism - physiopathology ; Alcoholism and acute alcohol poisoning ; Biological and medical sciences ; Cocaine Dependence ; Cocaine-Related Disorders - complications ; Cocaine-Related Disorders - genetics ; Cocaine-Related Disorders - physiopathology ; Drug addictions ; Gene Frequency - genetics ; Genetic Association ; Genetic Variation - genetics ; Humans ; Medical sciences ; Neuropeptide Y ; Phenotype ; Polymorphism, Single Nucleotide - genetics ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Receptors, Neuropeptide Y - genetics ; Substance Withdrawal Syndrome - complications ; Substance Withdrawal Syndrome - genetics ; Substance Withdrawal Syndrome - physiopathology ; Toxicology ; Withdrawal</subject><ispartof>Alcoholism, clinical and experimental research, 2008-12, Vol.32 (12), p.2031-2040</ispartof><rights>Copyright © 2008 by the Research Society on Alcoholism</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5710-bd4d24c3af77cf26a72e716f56038f10a799eaa7b9a6de838d4186afe44cba553</citedby><cites>FETCH-LOGICAL-c5710-bd4d24c3af77cf26a72e716f56038f10a799eaa7b9a6de838d4186afe44cba553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1530-0277.2008.00790.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1530-0277.2008.00790.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20977375$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18828811$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wetherill, Leah</creatorcontrib><creatorcontrib>Schuckit, Marc A.</creatorcontrib><creatorcontrib>Hesselbrock, Victor</creatorcontrib><creatorcontrib>Xuei, Xiaoling</creatorcontrib><creatorcontrib>Liang, Tiebing</creatorcontrib><creatorcontrib>Dick, Danielle M.</creatorcontrib><creatorcontrib>Kramer, John</creatorcontrib><creatorcontrib>Nurnberger Jr, John I.</creatorcontrib><creatorcontrib>Tischfield, Jay A.</creatorcontrib><creatorcontrib>Porjesz, Bernice</creatorcontrib><creatorcontrib>Edenberg, Howard J.</creatorcontrib><creatorcontrib>Foroud, Tatiana</creatorcontrib><title>Neuropeptide Y Receptor Genes Are Associated With Alcohol Dependence, Alcohol Withdrawal Phenotypes, and Cocaine Dependence</title><title>Alcoholism, clinical and experimental research</title><addtitle>Alcohol Clin Exp Res</addtitle><description>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.</description><subject>Addictive behaviors</subject><subject>Adult and adolescent clinical studies</subject><subject>Alcoholism</subject><subject>Alcoholism - complications</subject><subject>Alcoholism - genetics</subject><subject>Alcoholism - physiopathology</subject><subject>Alcoholism and acute alcohol poisoning</subject><subject>Biological and medical sciences</subject><subject>Cocaine Dependence</subject><subject>Cocaine-Related Disorders - complications</subject><subject>Cocaine-Related Disorders - genetics</subject><subject>Cocaine-Related Disorders - physiopathology</subject><subject>Drug addictions</subject><subject>Gene Frequency - genetics</subject><subject>Genetic Association</subject><subject>Genetic Variation - genetics</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Neuropeptide Y</subject><subject>Phenotype</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Receptors, Neuropeptide Y - genetics</subject><subject>Substance Withdrawal Syndrome - complications</subject><subject>Substance Withdrawal Syndrome - genetics</subject><subject>Substance Withdrawal Syndrome - physiopathology</subject><subject>Toxicology</subject><subject>Withdrawal</subject><issn>0145-6008</issn><issn>1530-0277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU-P0zAQxSMEYsvCV0C-wGkTbOePnQNIUdgtSKtSrUArTtbUmVCXNA52yrbaL78JrcJywxePPL_3ZqwXBITRiA3n3SZiaUxDyoWIOKUyolTkNNo_CWZT42kwoyxJw2zonwUvvN9QShOZZc-DMyYll5KxWXC_wJ2zHXa9qZB8Jzeoh9o6MscWPSkcksJ7qw30WJFb069J0Wi7tg35iB22FbYaL6a3Eagc3EFDlmtsbX_o0F8QaCtSWg2mxUeyl8GzGhqPr073efDt6vJr-Sm8_jL_XBbXoU4Fo-GqSiqe6BhqIXTNMxAcBcvqNKOxrBkFkecIIFY5ZBXKWFYJkxnUmCR6BWkanwcfjr7dbrXFSmPbO2hU58wW3EFZMOrfTmvW6of9rXiW0iRhg8Hbk4Gzv3boe7U1XmPTQIt25xWnPGeM8gGUR1A7673DehrCqBqTUxs1BqTGgNSYnPqTnNoP0tePl_wrPEU1AG9OAHgNTe2g1cZPHKe5ELEYf_v-yN2ZBg__vYAqysuboRr04VFvfI_7SQ_up8rGAep2MVflki_KqzJXy_gBN5rFyw</recordid><startdate>200812</startdate><enddate>200812</enddate><creator>Wetherill, Leah</creator><creator>Schuckit, Marc A.</creator><creator>Hesselbrock, Victor</creator><creator>Xuei, Xiaoling</creator><creator>Liang, Tiebing</creator><creator>Dick, Danielle M.</creator><creator>Kramer, John</creator><creator>Nurnberger Jr, John I.</creator><creator>Tischfield, Jay A.</creator><creator>Porjesz, Bernice</creator><creator>Edenberg, Howard J.</creator><creator>Foroud, Tatiana</creator><general>Blackwell Publishing Ltd</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>200812</creationdate><title>Neuropeptide Y Receptor Genes Are Associated With Alcohol Dependence, Alcohol Withdrawal Phenotypes, and Cocaine Dependence</title><author>Wetherill, Leah ; Schuckit, Marc A. ; Hesselbrock, Victor ; Xuei, Xiaoling ; Liang, Tiebing ; Dick, Danielle M. ; Kramer, John ; Nurnberger Jr, John I. ; Tischfield, Jay A. ; Porjesz, Bernice ; Edenberg, Howard J. ; Foroud, Tatiana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5710-bd4d24c3af77cf26a72e716f56038f10a799eaa7b9a6de838d4186afe44cba553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Addictive behaviors</topic><topic>Adult and adolescent clinical studies</topic><topic>Alcoholism</topic><topic>Alcoholism - complications</topic><topic>Alcoholism - genetics</topic><topic>Alcoholism - physiopathology</topic><topic>Alcoholism and acute alcohol poisoning</topic><topic>Biological and medical sciences</topic><topic>Cocaine Dependence</topic><topic>Cocaine-Related Disorders - complications</topic><topic>Cocaine-Related Disorders - genetics</topic><topic>Cocaine-Related Disorders - physiopathology</topic><topic>Drug addictions</topic><topic>Gene Frequency - genetics</topic><topic>Genetic Association</topic><topic>Genetic Variation - genetics</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Neuropeptide Y</topic><topic>Phenotype</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Receptors, Neuropeptide Y - genetics</topic><topic>Substance Withdrawal Syndrome - complications</topic><topic>Substance Withdrawal Syndrome - genetics</topic><topic>Substance Withdrawal Syndrome - physiopathology</topic><topic>Toxicology</topic><topic>Withdrawal</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wetherill, Leah</creatorcontrib><creatorcontrib>Schuckit, Marc A.</creatorcontrib><creatorcontrib>Hesselbrock, Victor</creatorcontrib><creatorcontrib>Xuei, Xiaoling</creatorcontrib><creatorcontrib>Liang, Tiebing</creatorcontrib><creatorcontrib>Dick, Danielle M.</creatorcontrib><creatorcontrib>Kramer, John</creatorcontrib><creatorcontrib>Nurnberger Jr, John I.</creatorcontrib><creatorcontrib>Tischfield, Jay A.</creatorcontrib><creatorcontrib>Porjesz, Bernice</creatorcontrib><creatorcontrib>Edenberg, Howard J.</creatorcontrib><creatorcontrib>Foroud, Tatiana</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Alcoholism, clinical and experimental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wetherill, Leah</au><au>Schuckit, Marc A.</au><au>Hesselbrock, Victor</au><au>Xuei, Xiaoling</au><au>Liang, Tiebing</au><au>Dick, Danielle M.</au><au>Kramer, John</au><au>Nurnberger Jr, John I.</au><au>Tischfield, Jay A.</au><au>Porjesz, Bernice</au><au>Edenberg, Howard J.</au><au>Foroud, Tatiana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuropeptide Y Receptor Genes Are Associated With Alcohol Dependence, Alcohol Withdrawal Phenotypes, and Cocaine Dependence</atitle><jtitle>Alcoholism, clinical and experimental research</jtitle><addtitle>Alcohol Clin Exp Res</addtitle><date>2008-12</date><risdate>2008</risdate><volume>32</volume><issue>12</issue><spage>2031</spage><epage>2040</epage><pages>2031-2040</pages><issn>0145-6008</issn><eissn>1530-0277</eissn><coden>ACRSDM</coden><abstract>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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>18828811</pmid><doi>10.1111/j.1530-0277.2008.00790.x</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Addictive behaviors Adult and adolescent clinical studies Alcoholism Alcoholism - complications Alcoholism - genetics Alcoholism - physiopathology Alcoholism and acute alcohol poisoning Biological and medical sciences Cocaine Dependence Cocaine-Related Disorders - complications Cocaine-Related Disorders - genetics Cocaine-Related Disorders - physiopathology Drug addictions Gene Frequency - genetics Genetic Association Genetic Variation - genetics Humans Medical sciences Neuropeptide Y Phenotype Polymorphism, Single Nucleotide - genetics Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Receptors, Neuropeptide Y - genetics Substance Withdrawal Syndrome - complications Substance Withdrawal Syndrome - genetics Substance Withdrawal Syndrome - physiopathology Toxicology Withdrawal |
| title | Neuropeptide Y Receptor Genes Are Associated With Alcohol Dependence, Alcohol Withdrawal Phenotypes, and Cocaine Dependence |
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