Genomic influences on alcohol problems in a population-based sample of young adults

Basit Öğe Kaydı
dc.authoridEvans, David/0000-0003-0663-4621
dc.authoridWolen, Aaron/0000-0003-2542-2202
dc.authoridHickman, Matthew/0000-0001-9864-459X
dc.authoridSalvatore, Jessica/0000-0001-5504-5087
dc.authoridEdwards, Alexis/0000-0002-4006-9710
dc.contributor.authorEdwards, Alexis C.
dc.contributor.authorAliev, Fazil
dc.contributor.authorWolen, Aaron R.
dc.contributor.authorSalvatore, Jessica E.
dc.contributor.authorGardner, Charles O.
dc.contributor.authorMcMahon, George
dc.contributor.authorEvans, David M.
dc.date.accessioned2024-09-29T16:04:33Z
dc.date.available2024-09-29T16:04:33Z
dc.date.issued2015
dc.departmentKarabük Üniversitesien_US
dc.description.abstractAimsAlcohol problems (AP) contribute substantially to the global disease burden. Twin and family studies suggest that AP are genetically influenced, although few studies have identified variants or genes that are robustly associated with risk. This study identifies genetic and genomic influences on AP during young adulthood, which is often when drinking habits are established. DesignWe conducted a genome-wide association study of AP. We further conducted gene-based tests, gene ontology analyses and functional genomic enrichment analyses to assess genomic factors beyond single variants that are relevant to AP. SettingThe Avon Longitudinal Study of Parents and Children, a large population-based study of a UK birth cohort. ParticipantsGenetic and phenotypical data were available for 4304 participants. MeasurementsThe AP phenotype was a factor score derived from items from the Alcohol Use Disorders Identification Test, symptoms of DSM-IV alcohol dependence, and three additional problem-related items. FindingsOne variant met genome-wide significance criteria. Four out of 22880 genes subjected to gene-based analyses survived a stringent significance threshold (q<0.05); none of these have been implicated previously in alcohol-related phenotypes. Several biologically plausible gene ontologies were statistically over-represented among implicated single nucleotide polymorphisms (SNPs). SNPs on the Illumina 550K SNP chip accounted for similar to 5% of the phenotypical variance in AP. ConclusionsGenetic and genomic factors appear to play a role in alcohol problems in young adults. Genes involved in nervous system-related processes, such as signal transduction and neurogenesis, potentially contribute to liability to alcohol problems, as do genes expressed in non-brain tissues.en_US
dc.description.sponsorshipUK Medical Research Council; Wellcome Trust [092731, 074268/Z/07/Z]; University of Bristol; National Institutes of Health [K01AA021399, T32MH020030, UL1RR031990, K02AA018755, F32AA22269, R01AA018333]; MRC [G0800612, MC_UU_12013/4, MR/K023233/1, MR/L022206/1, G0802736] Funding Source: UKRIen_US
dc.description.sponsorshipWe are grateful to all the families who took part in this study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. ALSPAC GWAS data were generated by Sample Logistics and Genotyping Facilities at the Wellcome Trust Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. The UK Medical Research Council and the Wellcome Trust (grant refs: 092731 and 074268/Z/07/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and the corresponding author will serve as guarantor for the contents of this paper. This research was specifically funded by the National Institutes of Health (K01AA021399, T32MH020030, UL1RR031990, K02AA018755, F32AA22269 and R01AA018333).en_US
dc.identifier.doi10.1111/add.12822
dc.identifier.endpage470en_US
dc.identifier.issn0965-2140
dc.identifier.issn1360-0443
dc.identifier.issue3en_US
dc.identifier.pmid25439982en_US
dc.identifier.scopus2-s2.0-84922651536en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage461en_US
dc.identifier.urihttps://doi.org/10.1111/add.12822
dc.identifier.urihttps://hdl.handle.net/20.500.14619/6203
dc.identifier.volume110en_US
dc.identifier.wosWOS:000350101200019en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofAddictionen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAlcohol problemsen_US
dc.subjectALSPACen_US
dc.subjectepigentic enrichmenten_US
dc.subjectgene-based testen_US
dc.subjectGWASen_US
dc.subjectpolygenicen_US
dc.titleGenomic influences on alcohol problems in a population-based sample of young adultsen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu