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dc.contributor.authorSalvatore, Jessica E.
dc.contributor.authorSavage, Jeanne E.
dc.contributor.authorBarr, Peter
dc.contributor.authorWolen, Aaron R.
dc.contributor.authorAliev, Fazil
dc.contributor.authorVuoskimaa, Eero
dc.contributor.authorLatvala, Antti
dc.contributor.authorPulkkinen, Lea
dc.contributor.authorRose, Richard J.
dc.contributor.authorKaprio, Jaakko
dc.contributor.authorDick, Danielle M.
dc.date.accessioned2018-01-31T10:08:40Z
dc.date.available2018-11-11T22:35:41Z
dc.date.issued2018
dc.identifier.citationSalvatore, J. E., Savage, J. E., Barr, P., Wolen, A. R., Aliev, F., Vuoskimaa, E., Latvala, A., Pulkkinen, L., Rose, R. J., Kaprio, J., & Dick, D. M. (2018). Incorporating functional genomic information to enhance polygenic signal and identify variants involved in gene-by-environment interaction for young adult alcohol problems. <i>Alcoholism : Clinical and Experimental Research</i>, <i>42</i>(2), 413-423. <a href="https://doi.org/10.1111/acer.13551" target="_blank">https://doi.org/10.1111/acer.13551</a>
dc.identifier.otherCONVID_27354514
dc.identifier.otherTUTKAID_75706
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/56963
dc.description.abstractBackground Characterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene-by-environment (G × E) interaction effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit G × E effects. Methods We examined these questions in the young adult FinnTwin12 sample (n = 1,170). We used genomewide association estimates from an independent sample to derive 2 types of polygenic scores for alcohol problems in FinnTwin12. Genomewide polygenic scores included all SNPs surpassing a designated p-value threshold. DNase polygenic scores were a subset of the genomewide polygenic scores including only variants in DNase I hypersensitive sites (DHSs), which are open chromatin marks likely to index regions with a regulatory function. We conducted parallel analyses using height as a nonpsychiatric model phenotype to evaluate the consistency of effects. For the G × E analyses, we examined whether SNPs in DHSs were overrepresented among SNPs demonstrating significant G × E effects in an interaction between romantic relationship status and intoxication frequency. Results Contrary to our expectations, we found that DNase polygenic scores were not more strongly predictive of alcohol problems than conventional polygenic scores. However, variants in DNase polygenic scores had per-SNP effects that were up to 1.4 times larger than variants in conventional polygenic scores. This same pattern of effects was also observed in supplementary analyses with height. In G × E models, SNPs in DHSs were modestly overrepresented among SNPs with significant interaction effects for intoxication frequency. Conclusions These findings highlight the potential utility of integrating functional genomic annotation information to increase the signal-to-noise ratio in polygenic scores and identify genetic variants that may be most susceptible to environmental modification.
dc.language.isoeng
dc.publisherSociety on Alcoholism; John Wiley & Sons, Inc.
dc.relation.ispartofseriesAlcoholism : Clinical and Experimental Research
dc.subject.otheralcohol
dc.subject.otherfunctional genomics
dc.subject.othergene-environment interplay
dc.subject.otherpolygenic scores
dc.titleIncorporating functional genomic information to enhance polygenic signal and identify variants involved in gene-by-environment interaction for young adult alcohol problems
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201801301380
dc.contributor.laitosPsykologian laitosfi
dc.contributor.laitosDepartment of Psychologyen
dc.contributor.oppiainePsykologiafi
dc.contributor.oppiainePsychologyen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2018-01-30T13:15:16Z
dc.type.coarhttp://purl.org/coar/resource_type/c_2df8fbb1
dc.description.reviewstatuspeerReviewed
dc.format.pagerange413-423
dc.relation.issn0145-6008
dc.relation.numberinseries2
dc.relation.volume42
dc.type.versionacceptedVersion
dc.rights.copyright© 2017 by the Research Society on Alcoholism. This is a final draft version of an article whose final and definitive form has been published by Research Society on Alcoholism. Published in this repository with the kind permission of the publisher.
dc.rights.accesslevelopenAccessfi
dc.subject.ysoalkoholiongelmat
dc.subject.ysonuoret aikuiset
dc.subject.ysogeneettiset tekijät
dc.subject.ysoympäristötekijät
dc.subject.ysogenomiikka
jyx.subject.urihttp://www.yso.fi/onto/yso/p9143
jyx.subject.urihttp://www.yso.fi/onto/yso/p15979
jyx.subject.urihttp://www.yso.fi/onto/yso/p21661
jyx.subject.urihttp://www.yso.fi/onto/yso/p6194
jyx.subject.urihttp://www.yso.fi/onto/yso/p5146
dc.relation.doi10.1111/acer.13551
dc.type.okmA1


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