Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures
Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was as...
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| Veröffentlicht in: | Translational psychiatry 2016-03, Vol.6 (3), p.e761-e761 |
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| creator | Kapoor, M Chou, Y-L Edenberg, H J Foroud, T Martin, N G Madden, P A F Wang, J C Bertelsen, S Wetherill, L Brooks, A Chan, G Hesselbrock, V Kuperman, S Medland, S E Montgomery, G Tischfield, J Whitfield, J B Bierut, L J Heath, A C Bucholz, K K Goate, A M Agrawal, A |
| description | Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples—the Study of Addictions: Genes and Environment (SAGE;
n=
2336) and an Australian sample (OZ-ALC;
n=
5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement. |
| doi_str_mv | 10.1038/tp.2016.27 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4872451</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1775633584</sourcerecordid><originalsourceid>FETCH-LOGICAL-c414t-c0eeff0a4809649bc473fb23ae7f0d9899c9976f1e4a07e0673f2175757da8b23</originalsourceid><addsrcrecordid>eNptkU9LBCEchiWKiq1LHyA8RjGbzjijcwki-gcLXeosrvNz15jRSZ2ib5-xFQUpqPA-PIovQkeUzCmpxHka5yWhzbzkW2i_pLUoKirE9q_zHjqM8ZnkUTNBOd1FeyUnJEd8H73cgvMDFG-2Azz6_n0FzmoctQ8QsfEBqxVglbB3EfJqsOq1X_sedzCC68DpHLsOqxi9tipZ7_CbTetvrgjQqwQdHkDFKUsP0I5RfYTDr32Gnm6uH6_uisXD7f3V5aLQjLJUaAJgDFFMkLZh7VIzXpllWSnghnStaFvdtrwxFJgiHEiT45LyOs9OiQzO0MXGO07LAToNLgXVyzHYQYV36ZWVfxNn13LlXyUTvGQ1zYKTL0HwLxPEJAcbNfS9cuCnKCnndVNVtWAZPd2gOvgYA5ifayiRnzXJNMrPmmTJM3z8-2E_6HcpGTjbADFHbgVBPvspuPxZ_-k-AEGtnmU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1775633584</pqid></control><display><type>article</type><title>Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures</title><source>Nature Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Springer Nature OA/Free Journals</source><creator>Kapoor, M ; Chou, Y-L ; Edenberg, H J ; Foroud, T ; Martin, N G ; Madden, P A F ; Wang, J C ; Bertelsen, S ; Wetherill, L ; Brooks, A ; Chan, G ; Hesselbrock, V ; Kuperman, S ; Medland, S E ; Montgomery, G ; Tischfield, J ; Whitfield, J B ; Bierut, L J ; Heath, A C ; Bucholz, K K ; Goate, A M ; Agrawal, A</creator><creatorcontrib>Kapoor, M ; Chou, Y-L ; Edenberg, H J ; Foroud, T ; Martin, N G ; Madden, P A F ; Wang, J C ; Bertelsen, S ; Wetherill, L ; Brooks, A ; Chan, G ; Hesselbrock, V ; Kuperman, S ; Medland, S E ; Montgomery, G ; Tischfield, J ; Whitfield, J B ; Bierut, L J ; Heath, A C ; Bucholz, K K ; Goate, A M ; Agrawal, A</creatorcontrib><description>Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples—the Study of Addictions: Genes and Environment (SAGE;
n=
2336) and an Australian sample (OZ-ALC;
n=
5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.</description><identifier>ISSN: 2158-3188</identifier><identifier>EISSN: 2158-3188</identifier><identifier>DOI: 10.1038/tp.2016.27</identifier><identifier>PMID: 27003187</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 45/43 ; 631/208/212 ; 692/699/476/5 ; Adult ; Age of Onset ; Alcoholism - genetics ; Australia ; Behavioral Sciences ; Biological Psychology ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Multifactorial Inheritance ; Neurosciences ; Original ; original-article ; Pedigree ; Pharmacotherapy ; Phenotype ; Psychiatry ; United States ; White People</subject><ispartof>Translational psychiatry, 2016-03, Vol.6 (3), p.e761-e761</ispartof><rights>The Author(s) 2016</rights><rights>Copyright © 2016 Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-c0eeff0a4809649bc473fb23ae7f0d9899c9976f1e4a07e0673f2175757da8b23</citedby><cites>FETCH-LOGICAL-c414t-c0eeff0a4809649bc473fb23ae7f0d9899c9976f1e4a07e0673f2175757da8b23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872451/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872451/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27003187$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kapoor, M</creatorcontrib><creatorcontrib>Chou, Y-L</creatorcontrib><creatorcontrib>Edenberg, H J</creatorcontrib><creatorcontrib>Foroud, T</creatorcontrib><creatorcontrib>Martin, N G</creatorcontrib><creatorcontrib>Madden, P A F</creatorcontrib><creatorcontrib>Wang, J C</creatorcontrib><creatorcontrib>Bertelsen, S</creatorcontrib><creatorcontrib>Wetherill, L</creatorcontrib><creatorcontrib>Brooks, A</creatorcontrib><creatorcontrib>Chan, G</creatorcontrib><creatorcontrib>Hesselbrock, V</creatorcontrib><creatorcontrib>Kuperman, S</creatorcontrib><creatorcontrib>Medland, S E</creatorcontrib><creatorcontrib>Montgomery, G</creatorcontrib><creatorcontrib>Tischfield, J</creatorcontrib><creatorcontrib>Whitfield, J B</creatorcontrib><creatorcontrib>Bierut, L J</creatorcontrib><creatorcontrib>Heath, A C</creatorcontrib><creatorcontrib>Bucholz, K K</creatorcontrib><creatorcontrib>Goate, A M</creatorcontrib><creatorcontrib>Agrawal, A</creatorcontrib><title>Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures</title><title>Translational psychiatry</title><addtitle>Transl Psychiatry</addtitle><addtitle>Transl Psychiatry</addtitle><description>Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples—the Study of Addictions: Genes and Environment (SAGE;
n=
2336) and an Australian sample (OZ-ALC;
n=
5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.</description><subject>45</subject><subject>45/43</subject><subject>631/208/212</subject><subject>692/699/476/5</subject><subject>Adult</subject><subject>Age of Onset</subject><subject>Alcoholism - genetics</subject><subject>Australia</subject><subject>Behavioral Sciences</subject><subject>Biological Psychology</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Multifactorial Inheritance</subject><subject>Neurosciences</subject><subject>Original</subject><subject>original-article</subject><subject>Pedigree</subject><subject>Pharmacotherapy</subject><subject>Phenotype</subject><subject>Psychiatry</subject><subject>United States</subject><subject>White People</subject><issn>2158-3188</issn><issn>2158-3188</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNptkU9LBCEchiWKiq1LHyA8RjGbzjijcwki-gcLXeosrvNz15jRSZ2ib5-xFQUpqPA-PIovQkeUzCmpxHka5yWhzbzkW2i_pLUoKirE9q_zHjqM8ZnkUTNBOd1FeyUnJEd8H73cgvMDFG-2Azz6_n0FzmoctQ8QsfEBqxVglbB3EfJqsOq1X_sedzCC68DpHLsOqxi9tipZ7_CbTetvrgjQqwQdHkDFKUsP0I5RfYTDr32Gnm6uH6_uisXD7f3V5aLQjLJUaAJgDFFMkLZh7VIzXpllWSnghnStaFvdtrwxFJgiHEiT45LyOs9OiQzO0MXGO07LAToNLgXVyzHYQYV36ZWVfxNn13LlXyUTvGQ1zYKTL0HwLxPEJAcbNfS9cuCnKCnndVNVtWAZPd2gOvgYA5ifayiRnzXJNMrPmmTJM3z8-2E_6HcpGTjbADFHbgVBPvspuPxZ_-k-AEGtnmU</recordid><startdate>20160322</startdate><enddate>20160322</enddate><creator>Kapoor, M</creator><creator>Chou, Y-L</creator><creator>Edenberg, H J</creator><creator>Foroud, T</creator><creator>Martin, N G</creator><creator>Madden, P A F</creator><creator>Wang, J C</creator><creator>Bertelsen, S</creator><creator>Wetherill, L</creator><creator>Brooks, A</creator><creator>Chan, G</creator><creator>Hesselbrock, V</creator><creator>Kuperman, S</creator><creator>Medland, S E</creator><creator>Montgomery, G</creator><creator>Tischfield, J</creator><creator>Whitfield, J B</creator><creator>Bierut, L J</creator><creator>Heath, A C</creator><creator>Bucholz, K K</creator><creator>Goate, A M</creator><creator>Agrawal, A</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160322</creationdate><title>Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures</title><author>Kapoor, M ; Chou, Y-L ; Edenberg, H J ; Foroud, T ; Martin, N G ; Madden, P A F ; Wang, J C ; Bertelsen, S ; Wetherill, L ; Brooks, A ; Chan, G ; Hesselbrock, V ; Kuperman, S ; Medland, S E ; Montgomery, G ; Tischfield, J ; Whitfield, J B ; Bierut, L J ; Heath, A C ; Bucholz, K K ; Goate, A M ; Agrawal, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-c0eeff0a4809649bc473fb23ae7f0d9899c9976f1e4a07e0673f2175757da8b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>45</topic><topic>45/43</topic><topic>631/208/212</topic><topic>692/699/476/5</topic><topic>Adult</topic><topic>Age of Onset</topic><topic>Alcoholism - genetics</topic><topic>Australia</topic><topic>Behavioral Sciences</topic><topic>Biological Psychology</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Multifactorial Inheritance</topic><topic>Neurosciences</topic><topic>Original</topic><topic>original-article</topic><topic>Pedigree</topic><topic>Pharmacotherapy</topic><topic>Phenotype</topic><topic>Psychiatry</topic><topic>United States</topic><topic>White People</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kapoor, M</creatorcontrib><creatorcontrib>Chou, Y-L</creatorcontrib><creatorcontrib>Edenberg, H J</creatorcontrib><creatorcontrib>Foroud, T</creatorcontrib><creatorcontrib>Martin, N G</creatorcontrib><creatorcontrib>Madden, P A F</creatorcontrib><creatorcontrib>Wang, J C</creatorcontrib><creatorcontrib>Bertelsen, S</creatorcontrib><creatorcontrib>Wetherill, L</creatorcontrib><creatorcontrib>Brooks, A</creatorcontrib><creatorcontrib>Chan, G</creatorcontrib><creatorcontrib>Hesselbrock, V</creatorcontrib><creatorcontrib>Kuperman, S</creatorcontrib><creatorcontrib>Medland, S E</creatorcontrib><creatorcontrib>Montgomery, G</creatorcontrib><creatorcontrib>Tischfield, J</creatorcontrib><creatorcontrib>Whitfield, J B</creatorcontrib><creatorcontrib>Bierut, L J</creatorcontrib><creatorcontrib>Heath, A C</creatorcontrib><creatorcontrib>Bucholz, K K</creatorcontrib><creatorcontrib>Goate, A M</creatorcontrib><creatorcontrib>Agrawal, A</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Translational psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kapoor, M</au><au>Chou, Y-L</au><au>Edenberg, H J</au><au>Foroud, T</au><au>Martin, N G</au><au>Madden, P A F</au><au>Wang, J C</au><au>Bertelsen, S</au><au>Wetherill, L</au><au>Brooks, A</au><au>Chan, G</au><au>Hesselbrock, V</au><au>Kuperman, S</au><au>Medland, S E</au><au>Montgomery, G</au><au>Tischfield, J</au><au>Whitfield, J B</au><au>Bierut, L J</au><au>Heath, A C</au><au>Bucholz, K K</au><au>Goate, A M</au><au>Agrawal, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures</atitle><jtitle>Translational psychiatry</jtitle><stitle>Transl Psychiatry</stitle><addtitle>Transl Psychiatry</addtitle><date>2016-03-22</date><risdate>2016</risdate><volume>6</volume><issue>3</issue><spage>e761</spage><epage>e761</epage><pages>e761-e761</pages><issn>2158-3188</issn><eissn>2158-3188</eissn><abstract>Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples—the Study of Addictions: Genes and Environment (SAGE;
n=
2336) and an Australian sample (OZ-ALC;
n=
5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27003187</pmid><doi>10.1038/tp.2016.27</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 45 45/43 631/208/212 692/699/476/5 Adult Age of Onset Alcoholism - genetics Australia Behavioral Sciences Biological Psychology Female Genetic Predisposition to Disease Genome-Wide Association Study Humans Male Medicine Medicine & Public Health Middle Aged Multifactorial Inheritance Neurosciences Original original-article Pedigree Pharmacotherapy Phenotype Psychiatry United States White People |
| title | Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures |
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