dc.contributor.author |
Hibberd, Rebecca |
|
dc.contributor.author |
Golovina, Evgeniia |
|
dc.contributor.author |
Farrow, Sophie |
|
dc.contributor.author |
O'Sullivan, Justin M |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2021-02-15T23:28:24Z |
|
dc.date.available |
2021-02-15T23:28:24Z |
|
dc.date.issued |
2020-6-18 |
|
dc.identifier.citation |
Scientific reports 10(1):9897 18 Jun 2020 |
|
dc.identifier.issn |
2045-2322 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/54465 |
|
dc.description.abstract |
GWAS studies have identified genetic variants associated with Alcohol Dependence (AD), but how they link to genes, their regulation and disease traits, remains largely unexplored. Here we integrated information on the 3D genome organization with expression quantitative loci (eQTLs) analysis, using CoDeS3D, to identify the functional impacts of single nucleotide polymorphisms associated with AD (p < 1 × 10<sup>-6</sup>). We report that 42% of the 285 significant tissue-specific regulatory interactions we identify were associated with four genes encoding Alcohol Dehydrogenase - ADH1A, ADH1B, ADH1C and ADH4. Identified eQTLs produced a co-ordinated regulatory action between ADH genes, especially between ADH1A and ADH1C within the subcutaneous adipose and gastrointestinal tissues. Five eQTLs were associated with regulatory motif alterations and tissue-specific histone marks consistent with these variants falling in enhancer and promoter regions. By contrast, few regulatory connections were identified in the stomach and liver. This suggests that changes in gene regulation associated with AD are linked to changes in tissues other than the primary sites of alcohol absorption and metabolism. Future work to functionally characterise the putative regulatory regions we have identified and their links to metabolic and regulatory changes in genes will improve our mechanistic understanding of AD disease development and progression. |
|
dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
Springer Science and Business Media LLC |
|
dc.relation.ispartofseries |
Scientific reports |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Gastrointestinal Tract |
|
dc.subject |
Lung |
|
dc.subject |
Adipose Tissue |
|
dc.subject |
Humans |
|
dc.subject |
Alcoholism |
|
dc.subject |
Alcohol Dehydrogenase |
|
dc.subject |
Genotype |
|
dc.subject |
Linkage Disequilibrium |
|
dc.subject |
Polymorphism, Single Nucleotide |
|
dc.subject |
Quantitative Trait Loci |
|
dc.subject |
Genome-Wide Association Study |
|
dc.subject |
Adipose Tissue |
|
dc.subject |
Alcohol Dehydrogenase |
|
dc.subject |
Alcoholism |
|
dc.subject |
Gastrointestinal Tract |
|
dc.subject |
Genome-Wide Association Study |
|
dc.subject |
Genotype |
|
dc.subject |
Humans |
|
dc.subject |
Linkage Disequilibrium |
|
dc.subject |
Lung |
|
dc.subject |
Polymorphism, Single Nucleotide |
|
dc.subject |
Quantitative Trait Loci |
|
dc.subject |
Science & Technology |
|
dc.subject |
Multidisciplinary Sciences |
|
dc.subject |
Science & Technology - Other Topics |
|
dc.subject |
GENOME-WIDE ASSOCIATION |
|
dc.subject |
GWAS |
|
dc.subject |
RISK |
|
dc.subject |
SNPS |
|
dc.subject |
DISCOVERY |
|
dc.subject |
HAPLOREG |
|
dc.subject |
TRAITS |
|
dc.subject |
0604 Genetics |
|
dc.subject |
Biomedical |
|
dc.subject |
Basic Science |
|
dc.subject |
Alcoholism, Alcohol Use and Health |
|
dc.subject |
Substance Abuse |
|
dc.subject |
Human Genome |
|
dc.subject |
Genetics |
|
dc.subject |
Brain Disorders |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.title |
Genetic variants associated with alcohol dependence co-ordinate regulation of ADH genes in gastrointestinal and adipose tissues. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1038/s41598-020-66048-z |
|
pubs.issue |
1 |
|
pubs.begin-page |
9897 |
|
pubs.volume |
10 |
|
dc.date.updated |
2021-01-31T01:43:19Z |
|
dc.rights.holder |
Copyright: The authors |
en |
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/32555468 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.subtype |
Research Support, N.I.H., Extramural |
|
pubs.elements-id |
805414 |
|
dc.identifier.eissn |
2045-2322 |
|
dc.identifier.pii |
10.1038/s41598-020-66048-z |
|
pubs.number |
9897 |
|
pubs.online-publication-date |
2020-6-18 |
|