Curtis, D;
(2021)
Investigation of Association of Rare, Functional Genetic Variants With Heavy Drinking and Problem Drinking in Exome Sequenced UK Biobank Participants.
Alcohol and Alcoholism
10.1093/alcalc/agab031.
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Abstract
AIMS: The study aimed to identify specific genes and functional genetic variants affecting susceptibility to two alcohol-related phenotypes: heavy drinking and problem drinking. METHODS: Phenotypic and exome sequence data were downloaded from the UK Biobank. Reported drinks in the last 24 hours were used to define heavy drinking, while responses to a mental health questionnaire defined problem drinking. Gene-wise weighted burden analysis was applied, with genetic variants which were rarer and/or had a more severe functional effect being weighted more highly. Additionally, previously reported variants of interest were analysed inidividually. RESULTS: Of exome sequenced subjects, for heavy drinking, there were 8166 cases and 84,461 controls, while for problem drinking, there were 7811 cases and 59,606 controls. No gene was formally significant after correction for multiple testing, but three genes possibly related to autism were significant at P < 0.001, FOXP1, ARHGAP33 and CDH9, along with VGF which may also be of psychiatric interest. Well established associations with rs1229984 in ADH1B and rs671 in ALDH2 were confirmed, but previously reported variants in ALDH1B1 and GRM3 were not associated with either phenotype. CONCLUSIONS: This large study fails to conclusively implicate any novel genes or variants. It is possible that more definitive results will be obtained when sequence data for the remaining UK Biobank participants become available and/or if data can be obtained for a more extreme phenotype such as alcohol dependence disorder. This research has been conducted using the UK Biobank Resource.
Type: | Article |
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Title: | Investigation of Association of Rare, Functional Genetic Variants With Heavy Drinking and Problem Drinking in Exome Sequenced UK Biobank Participants |
Location: | England |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1093/alcalc/agab031 |
Publisher version: | https://doi.org/10.1093/alcalc/agab031 |
Language: | English |
Additional information: | Copyright © The Author(s) 2021. Medical Council on Alcohol and Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | alcohol abuse, ethanol, phenotype, autistic disorder, genes, genetics, heavy drinking, exome, biobanks |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
URI: | https://discovery.ucl.ac.uk/id/eprint/10128858 |
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