Meent, M. van de (Mette) (2017) Genetic variants of the alcohol dehydrogenase 1B gene and possible other genes as instrumental variables to assess the relation between alcohol consumption and cardiovascular disease and other disease outcomes and phenotypes. thesis, Medicine.
Full text available on request.Abstract
Introduction: Moderate intake of alcohol has been implicated in a wide-range of disease outcomes. Some relationships are firmly established such those between increased alcohol intake and higher risk of gout, whereas others are more controversial, such as the association between increased alcohol intake and cardiovascular disease (CVD). Previous Mendelian randomization studies have focused on single genetic variants only. In this study, we replicated analyses for one, often described, single nucleotide polymorphism (SNP) of the ADH1B gene and its association with a wide range of disease outcomes and phenotypes. Moreover, we sought to identify relationships between a multi variant weighted genetic risk score (GRS) of alcohol consumption and a wide range of disease outcomes and phenotypes. Methods: Previously identified variants for alcohol intake were tested for their association with alcohol consumption in 143,193 individuals of UK Biobank and used to construct a multi variant genetic risk score. Regression analysis was done to assess the association between the earlier described SNP and a wide-range of disease outcomes and phenotypes. This analysis was performed for the weighted GRS as well. Results: Four genetic variants were strongly associated with alcohol consumption in UK Biobank among which rs780094 (GCKR) was newly confirmed as an alcohol consumption locus. The earlier described ADH1B rs1229984 was associated with higher systolic blood pressures (P=1.34*10-6), higher odds of hypertension (P=2.11*10-6) and lower odds of gout (P=2.23*10-10). Similar results were found for the weighted GRS: the weighted GRS showed an association with higher systolic blood pressures (P=7.03*10-6), higher odds of hypertension (P=1.21*10-5) and lower odds of gout (P=1.14*10-13). Conclusions: This is the largest single study of genetic determined alcohol consumption to date. The ADH1B (rs1229984) and the weighted GRS consisting of multiple variants highlighted a yin and yang relationship between gout and alcohol, as genetic variants causing increased alcohol consumption are protective for gout. The ADH1B (rs1229984) and the weighted GRS also underlined potential harmful effects of alcohol intake in cardiovascular disease.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisor: and Harst, Prof. Dr. P. van der and Second supervisor: and Verweij, N. and Department: University Medical Center Groningen, Cardiology |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:45 |
| Last Modified: | 25 Jun 2020 10:45 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/625 |
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