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. 2021 Jun;13(12):939-951.
doi: 10.2217/epi-2021-0039. Epub 2021 May 17.

Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study

Meng Lu  1 , Qin Xueying  1   2 , Peng Hexiang  1 , Gao Wenjing  1 , Sara Hägg  2 , Cao Weihua  1 , Li Chunxiao  1 , Yu Canqing  1 , Lv Jun  1 , Pang Zengchang  3 , Cong Liming  4 , Wang Hua  5 , Wu Xianping  6 , Wang Yunzhang  2 , Li Liming  1
Affiliations

Genome-wide associations between alcohol consumption and blood DNA methylation: evidence from twin study

Meng Lu et al. Epigenomics. 2021 Jun.

Abstract

Aim: Alcohol intake alters DNA methylation profiles and methylation might mediate the association between alcohol and disease, but limited number of positive CpG sites repeatedly replicated. Materials & methods: In total, 57 monozygotic (MZ) twin pairs discordant for alcohol drinking from the Chinese National Twin Registry and 158 MZ and dizygotic twin pairs in the Swedish Adoption/Twin Study of Aging were evaluated. DNA methylation was detected using the Infinium HumanMethylation450 BeadChip. Results: Among candidate CpG sites, cg07326074 was significantly correlated with drinking after adjusting for covariates in MZ twins in both datasets but not in the entire sample or dizygotic twins. Conclusion: The hypermethylation of cg07326074, located in the tumor-promoting gene C16orf59, was associated with alcohol consumption.

Keywords: C16orf59; CARD10; CpG sites; DNA methylation; alcohol; discordant twin design; hypermethylation.

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Conflict of interest statement

Financial & competing interests disclosure

This study was supported by National Natural Science Foundation of China (82073633, 81973126, 81573223) and special fund for Health scientific research in the public welfare (201502006, 201002007). SATSA was funded by NIH (grants AG04563 and AG10175), the MacArthur Foundation Research Network on Successful Aging, the Swedish Research Council for Working Life and Social Research (FAS; grants 97:0147:1B, 2009-0795) and the Swedish Research Council (825-2007-7460 and 825-2009-6141). This work was supported by the Swedish Research Council (2015-03255), The Foundation for Gamla Tjänarinnor (2018-00688), the KI Foundation, the Strategic Research Area in Epidemiology at Karolinska Institutet, Erik Rönnbergs donation for scientific studies in aging and age-related diseases. X Qin was supported by King Gustaf V’s and Queen Victorias Freemason Foundation, The Foundation for Gamla Tjänarinnor (2018-00688), and the China Scholarship Council for one year study at Karolinska Institutet between 2020 and 2021. The SNP&SEQ Platform is also supported by the Swedish Research Council and the Knut and Alice Wallenberg Foundation. The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no 2017-00641. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript by Editage using funding from National Natural Science Foundation of China (82073633, 81973126, 81573223).

Figures

Figure 1.
Figure 1.. Genome-wide CpG sites associated with alcohol intake.
(A) Discovery population, model 1, adjusting age, sex, BMI and surrogate variable as mixed effect, twin identity number as random effect; (B) discovery population, model 2, additional adjusted with smoking based on model 1; (C) difference ≥40 g/day group, model 1,adjusting age, sex, BMI and surrogate variable as mixed effect, twin identity number as random effect.
Figure 2.
Figure 2.. Volcanic plot of monozygotic discordant for drinking.
(A) Discovery population, model 1; (B) Discovery population, model 2. (A) Volcanic plot in discovery population in model 1 adjusting age, sex, BMI and SVA as mixed effect, twin identity number as random effect. (B) model 2 additional adjusted with smoking based on model 1. The abscissa indicated the ratio of difference of the average β-value between the high drinking group and low drinking group for any CpG site to the low drinking group. The ordinate represented -log10 p-value calculated by Empirical Bayes paired moderated t-test. SVA: Surrogate variable.
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