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Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study
Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variati...
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| Published in: | Psychological medicine 2023-04, Vol.53 (6), p.2296-2306 |
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| container_end_page | 2306 |
| container_issue | 6 |
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| container_title | Psychological medicine |
| container_volume | 53 |
| creator | Schaefer, Jonathan D. Jang, Seon-Kyeong Clark, D. Angus Deak, Joseph D. Hicks, Brian M. Iacono, William G. Liu, Mengzhen McGue, Matt Vrieze, Scott I. Wilson, Sylia |
| description | Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation
demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.
PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (
= 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.
Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.
PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use. |
| doi_str_mv | 10.1017/S0033291721004116 |
| format | article |
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demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.
PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (
= 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.
Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.
PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.</description><identifier>ISSN: 0033-2917</identifier><identifier>ISSN: 1469-8978</identifier><identifier>EISSN: 1469-8978</identifier><identifier>DOI: 10.1017/S0033291721004116</identifier><identifier>PMID: 37310313</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Age ; Alcohol use ; Assortative mating ; Behavior ; Cannabis ; Consent ; Consortia ; Demography ; Disinhibition ; Drug use ; Families & family life ; Genealogy ; Genetic analysis ; Genetic diversity ; Genome-wide association studies ; Genomes ; Genomics ; Haplotypes ; Longitudinal studies ; Marijuana ; Mating ; Mental disorders ; Monozygotic ; Nicotine ; Older children ; Original ; Original Article ; Parents & parenting ; Population genetics ; Predictions ; Socioeconomic factors ; Stratification ; Structural equation modeling ; Substance abuse ; Substance use ; Twin studies ; Twins ; Young adults</subject><ispartof>Psychological medicine, 2023-04, Vol.53 (6), p.2296-2306</ispartof><rights>Copyright © The Author(s), 2021. Published by Cambridge University Press</rights><rights>Copyright © The Author(s), 2021. Published by Cambridge University Press. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2021 2021 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-81cba48ec0e2cabb9d13eed88dcd0e3b3a8fb5c2c590ad52bbfd9aee506fc94e3</citedby><cites>FETCH-LOGICAL-c472t-81cba48ec0e2cabb9d13eed88dcd0e3b3a8fb5c2c590ad52bbfd9aee506fc94e3</cites><orcidid>0000-0003-4112-9268</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2803773062/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$H</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2803773062?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,315,786,790,891,12873,21422,21423,27957,27958,31034,33646,33647,34565,34566,43768,44150,73317,74578,74996</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37310313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schaefer, Jonathan D.</creatorcontrib><creatorcontrib>Jang, Seon-Kyeong</creatorcontrib><creatorcontrib>Clark, D. Angus</creatorcontrib><creatorcontrib>Deak, Joseph D.</creatorcontrib><creatorcontrib>Hicks, Brian M.</creatorcontrib><creatorcontrib>Iacono, William G.</creatorcontrib><creatorcontrib>Liu, Mengzhen</creatorcontrib><creatorcontrib>McGue, Matt</creatorcontrib><creatorcontrib>Vrieze, Scott I.</creatorcontrib><creatorcontrib>Wilson, Sylia</creatorcontrib><title>Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study</title><title>Psychological medicine</title><addtitle>Psychol. Med</addtitle><description>Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation
demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.
PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (
= 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.
Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.
PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.</description><subject>Age</subject><subject>Alcohol use</subject><subject>Assortative mating</subject><subject>Behavior</subject><subject>Cannabis</subject><subject>Consent</subject><subject>Consortia</subject><subject>Demography</subject><subject>Disinhibition</subject><subject>Drug use</subject><subject>Families & family life</subject><subject>Genealogy</subject><subject>Genetic analysis</subject><subject>Genetic diversity</subject><subject>Genome-wide association studies</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Haplotypes</subject><subject>Longitudinal studies</subject><subject>Marijuana</subject><subject>Mating</subject><subject>Mental disorders</subject><subject>Monozygotic</subject><subject>Nicotine</subject><subject>Older children</subject><subject>Original</subject><subject>Original Article</subject><subject>Parents & parenting</subject><subject>Population genetics</subject><subject>Predictions</subject><subject>Socioeconomic factors</subject><subject>Stratification</subject><subject>Structural equation modeling</subject><subject>Substance abuse</subject><subject>Substance use</subject><subject>Twin studies</subject><subject>Twins</subject><subject>Young adults</subject><issn>0033-2917</issn><issn>1469-8978</issn><issn>1469-8978</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>7QJ</sourceid><sourceid>ALSLI</sourceid><sourceid>HEHIP</sourceid><recordid>eNp1UstuFDEQtBCIbAIfwAVZ4sIhA37Mw3NCUUQAKRIH4Dzyo2fWwWsvtifRfhT_iGd3CS9xarmqurpLbYSeUfKKEtq9_kQI56ynHaOE1JS2D9CK1m1fib4TD9FqoauFP0GnKd0QQjmt2WN0wjtOCad8hb5fpBS0ldkGn7CCfAfg8Ta43QTeahxt-orDiNOsUpZeA54TYOnNvhqbQjQQ94B0OqyDO8daei-VTed7uLiEbP2h0XosTXCQNCxeC78Ls58KOru8DsHsJdgFP9k8G-ulw_muYKm8dk_Qo1G6BE-P9Qx9uXr7-fJ9df3x3YfLi-tK1x3LlaBayVqAJsC0VKo3lAMYIYw2BLjiUoyq0Uw3PZGmYUqNppcADWlH3dfAz9Cbg-92VhswZdkcpRu20W5k3A1B2uFPxtv1MIXboZyFccF5cXh5dIjh2wwpDxtbQjsnPYQ5DUywpiE1axfpi7-kN2GOJfiiIrzrOGlZUdGDSseQUoTxfhtKlrHd8M9vKD3Pf49x3_Hz_EXAj6Zyo6I1E_ya_X_bH3sDxLs</recordid><startdate>20230401</startdate><enddate>20230401</enddate><creator>Schaefer, Jonathan D.</creator><creator>Jang, Seon-Kyeong</creator><creator>Clark, D. 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Angus ; Deak, Joseph D. ; Hicks, Brian M. ; Iacono, William G. ; Liu, Mengzhen ; McGue, Matt ; Vrieze, Scott I. ; Wilson, Sylia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c472t-81cba48ec0e2cabb9d13eed88dcd0e3b3a8fb5c2c590ad52bbfd9aee506fc94e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Age</topic><topic>Alcohol use</topic><topic>Assortative mating</topic><topic>Behavior</topic><topic>Cannabis</topic><topic>Consent</topic><topic>Consortia</topic><topic>Demography</topic><topic>Disinhibition</topic><topic>Drug use</topic><topic>Families & family life</topic><topic>Genealogy</topic><topic>Genetic analysis</topic><topic>Genetic diversity</topic><topic>Genome-wide association studies</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Haplotypes</topic><topic>Longitudinal studies</topic><topic>Marijuana</topic><topic>Mating</topic><topic>Mental disorders</topic><topic>Monozygotic</topic><topic>Nicotine</topic><topic>Older children</topic><topic>Original</topic><topic>Original Article</topic><topic>Parents & parenting</topic><topic>Population genetics</topic><topic>Predictions</topic><topic>Socioeconomic factors</topic><topic>Stratification</topic><topic>Structural equation modeling</topic><topic>Substance abuse</topic><topic>Substance use</topic><topic>Twin studies</topic><topic>Twins</topic><topic>Young adults</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schaefer, Jonathan D.</creatorcontrib><creatorcontrib>Jang, Seon-Kyeong</creatorcontrib><creatorcontrib>Clark, D. Angus</creatorcontrib><creatorcontrib>Deak, Joseph D.</creatorcontrib><creatorcontrib>Hicks, Brian M.</creatorcontrib><creatorcontrib>Iacono, William G.</creatorcontrib><creatorcontrib>Liu, Mengzhen</creatorcontrib><creatorcontrib>McGue, Matt</creatorcontrib><creatorcontrib>Vrieze, Scott I.</creatorcontrib><creatorcontrib>Wilson, Sylia</creatorcontrib><collection>Cambridge University Press:Open Access Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Applied Social Sciences Index & Abstracts (ASSIA)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>ProQuest Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Social Science Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Sociology Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database (ProQuest)</collection><collection>ProQuest Research Library</collection><collection>Sociology Database (ProQuest)</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Psychological medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schaefer, Jonathan D.</au><au>Jang, Seon-Kyeong</au><au>Clark, D. Angus</au><au>Deak, Joseph D.</au><au>Hicks, Brian M.</au><au>Iacono, William G.</au><au>Liu, Mengzhen</au><au>McGue, Matt</au><au>Vrieze, Scott I.</au><au>Wilson, Sylia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study</atitle><jtitle>Psychological medicine</jtitle><addtitle>Psychol. Med</addtitle><date>2023-04-01</date><risdate>2023</risdate><volume>53</volume><issue>6</issue><spage>2296</spage><epage>2306</epage><pages>2296-2306</pages><issn>0033-2917</issn><issn>1469-8978</issn><eissn>1469-8978</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Recent well-powered genome-wide association studies have enhanced prediction of substance use outcomes via polygenic scores (PGSs). Here, we test (1) whether these scores contribute to prediction over-and-above family history, (2) the extent to which PGS prediction reflects inherited genetic variation
demography (population stratification and assortative mating) and indirect genetic effects of parents (genetic nurture), and (3) whether PGS prediction is mediated by behavioral disinhibition prior to substance use onset.
PGSs for alcohol, cannabis, and nicotine use/use disorder were calculated for Minnesota Twin Family Study participants (
= 2483, 1565 monozygotic/918 dizygotic). Twins' parents were assessed for histories of substance use disorder. Twins were assessed for behavioral disinhibition at age 11 and substance use from ages 14 to 24. PGS prediction of substance use was examined using linear mixed-effects, within-twin pair, and structural equation models.
Nearly all PGS measures were associated with multiple types of substance use independently of family history. However, most within-pair PGS prediction estimates were substantially smaller than the corresponding between-pair estimates, suggesting that prediction is driven in part by demography and indirect genetic effects of parents. Path analyses indicated the effects of both PGSs and family history on substance use were mediated via disinhibition in preadolescence.
PGSs capturing risk of substance use and use disorder can be combined with family history measures to augment prediction of substance use outcomes. Results highlight indirect sources of genetic associations and preadolescent elevations in behavioral disinhibition as two routes through which these scores may relate to substance use.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>37310313</pmid><doi>10.1017/S0033291721004116</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-4112-9268</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Psychological medicine, 2023-04, Vol.53 (6), p.2296-2306 |
| issn | 0033-2917 1469-8978 1469-8978 |
| language | eng |
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| source | Applied Social Sciences Index & Abstracts (ASSIA); Social Science Premium Collection (Proquest) (PQ_SDU_P3); Sociology Collection; Cambridge University Press |
| subjects | Age Alcohol use Assortative mating Behavior Cannabis Consent Consortia Demography Disinhibition Drug use Families & family life Genealogy Genetic analysis Genetic diversity Genome-wide association studies Genomes Genomics Haplotypes Longitudinal studies Marijuana Mating Mental disorders Monozygotic Nicotine Older children Original Original Article Parents & parenting Population genetics Predictions Socioeconomic factors Stratification Structural equation modeling Substance abuse Substance use Twin studies Twins Young adults |
| title | Associations between polygenic risk of substance use and use disorder and alcohol, cannabis, and nicotine use in adolescence and young adulthood in a longitudinal twin study |
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