Dataset Information

Validation and characterisation of a DNA methylation alcohol biomarker across the life course.

ABSTRACT:

Background

Recently, an alcohol predictor was developed using DNA methylation at 144 CpG sites (DNAm-Alc) as a biomarker for improved clinical or epidemiologic assessment of alcohol-related ill health. We validate the performance and characterise the drivers of this DNAm-Alc for the first time in independent populations.

Results

In N = 1049 parents from the Avon Longitudinal Study of Parents and Children (ALSPAC) Accessible Resource for Integrated Epigenomic Studies (ARIES) at midlife, we found DNAm-Alc explained 7.6% of the variation in alcohol intake, roughly half of what had been reported previously, and interestingly explained a larger 9.8% of Alcohol Use Disorders Identification Test (AUDIT) score, a scale of alcohol use disorder. Explanatory capacity in participants from the offspring generation of ARIES measured during adolescence was much lower. However, DNAm-Alc explained 14.3% of the variation in replication using the Head and Neck 5000 (HN5000) clinical cohort that had higher average alcohol consumption. To investigate whether this relationship was being driven by genetic and/or earlier environment confounding, we examined how earlier versus concurrent DNAm-Alc measures predicted AUDIT scores. In both ARIES parental and offspring generations, we observed associations between AUDIT and concurrent, but not earlier DNAm-Alc, suggesting independence from genetic and stable environmental contributions.

Conclusions

The stronger relationship between DNAm-Alcs and AUDIT in parents at midlife compared to adolescents despite similar levels of consumption suggests that DNAm-Alc likely reflects long-term patterns of alcohol abuse. Such biomarkers may have potential applications for biomonitoring and risk prediction, especially in cases where reporting bias is a concern.

SUBMITTER: Yousefi PD

PROVIDER: S-EPMC6880546 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Validation and characterisation of a DNA methylation alcohol biomarker across the life course.

Yousefi Paul Darius PD Richmond Rebecca R Langdon Ryan R Ness Andrew A Liu Chunyu C Levy Daniel D Relton Caroline C Suderman Matthew M Zuccolo Luisa L

Clinical epigenetics 20191127 1

<h4>Background</h4>Recently, an alcohol predictor was developed using DNA methylation at 144 CpG sites (DNAm-Alc) as a biomarker for improved clinical or epidemiologic assessment of alcohol-related ill health. We validate the performance and characterise the drivers of this DNAm-Alc for the first time in independent populations.<h4>Results</h4>In N = 1049 parents from the Avon Longitudinal Study of Parents and Children (ALSPAC) Accessible Resource for Integrated Epigenomic Studies (ARIES) at mid ...[more]

PMID: 31775873

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Project description:Background and aimsAlcohol consumption changes markedly over the life course, with important implications for health and social development. Assessment of these patterns often relies on cross-sectional data, which cannot fully capture how individuals' drinking changes as they age. This study used data from 18 waves of a general population panel survey to measure drinking trajectories over the life course in Australia.Design and settingLongitudinal survey data from the Household, Income and Labour Dynamics in Australia (HILDA) survey between 2001 and 2018.ParticipantsA total of 20 593 individuals ages 15 or above in two samples assessing quantity-frequency (n = 20 569, 52.0% female) and risky single occasion drinking (RSOD), respectively, (n = 17 340, 52.5% female), interviewed as part of HILDA.MeasurementsUsual quantity of alcohol consumed per drinking occasion; frequency of drinking occasions per week; average daily consumption, calculated by combining reported usual quantity and frequency; and average reported frequency of RSOD per week.FindingsMultilevel, mixed effects models run with fractional polynomial terms found similar male and female alcohol consumption trajectories for quantity-frequency and RSOD measures. Usual quantity of alcohol consumed per drinking occasion (5.4 drinks for men, 3.8 for women) and RSOD frequency (0.56 occasions/week for men, 0.38 for women) peaked in young adulthood, whereas frequency of drinking occasions (2.5 occasions/week for men, 1.7 for women) peaked in middle age. Middle-age drinkers had the highest average daily consumption of alcohol (1.4 drinks/day for 54-year-old men, 0.6 drinks for 57-year-old women) and engaged in RSOD slightly less than young adults.ConclusionsAlcohol consumption in Australia appears to vary substantially over the life course, with usual quantity per drinking occasion and frequency of risky single occasion drinking peaking during early adulthood and average daily consumption and frequency of consumption peaking in middle age.

Project description:Early life stress (ELS) is associated with an increased risk of depression and this association may be mediated by epigenetic mechanisms. A previous epigenome-wide DNA methylation (DNAm) study investigating human newborns and two animal models of ELS suggested that the epigenetic regulator MORC1 is differentially methylated following ELS. The ELS-induced DNAm alterations were long-lasting in the animal models. However, whether this finding is also transferable to humans experiencing ELS in childhood was not investigated. Further, MORC1 may provide a link between ELS and adult depression, as MORC1 DNAm and genetic variants were found to be associated with depressive symptoms in humans. In the present study, we investigated the validity of MORC1 DNAm as a biomarker of ELS in humans and its role in linking ELS to depression later in life by studying childhood maltreatment. We analyzed whole blood MORC1 DNAm in an adult cohort (N = 151) that was characterized for both the presence of depressive symptoms and childhood maltreatment. Further, we investigated the association between MORC1 DNAm, depressive symptoms and childhood maltreatment in two additional cohorts (N = 299, N = 310). Overall, our data do not indicate an association of MORC1 DNAm with childhood maltreatment. An association of MORC1 DNAm with depressive symptoms was present in all cohorts, but was inconsistent in the specific CpG sites associated and the direction of effect (Tuebingen cohort: standardized β = 0.16, unstandardized β = 0.01, 95% CI [-0.0004, -0.0179], p = 0.061, PReDICT cohort: standardized β = -0.12, unstandardized β = -0.01, 95% CI [-0.0258, -0.0003], p = 0.045), Grady cohort: standardized β = 0.16, unstandardized β = 0.008, 95% CI [0.0019, 0.0143], p = 0.01). Our study thus suggests that peripheral MORC1 DNAm cannot serve as biomarker of childhood maltreatment in adults, but does provide further indication for the association of MORC1 DNAm with depressive symptoms.

Dataset Information

Validation and characterisation of a DNA methylation alcohol biomarker across the life course.

Background

Results

Conclusions

Publications

Validation and characterisation of a DNA methylation alcohol biomarker across the life course.

Similar Datasets

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