期刊
CLINICAL EPIGENETICS
卷 11, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13148-019-0753-7
关键词
ALSPAC; AUDIT; Prediction; CHARGE; Alcohol use disorder
资金
- UK Biotechnology and Biological Sciences Research Council
- Economic and Social Research Council Research Grant [ES/N000498/1]
- UK Medical Research Council fellowship [G0902144]
- UK Medical Research Council Integrative Epidemiology Unit [MC_UU_00011/1, MC_UU_00011/5]
- NIHR Bristol Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust
- University of Bristol
- UK Medical Research Council [102215/2/13/2]
- Wellcome [102215/2/13/2]
- UK BBSRC [BB/I025751/1, BB/I025263/1]
- National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme [RP-PG-0707-10034]
- BBSRC [BB/I025751/1, BB/I025263/1] Funding Source: UKRI
- ESRC [ES/N000498/1] Funding Source: UKRI
- MRC [G0902144, MC_UU_12013/1, MC_UU_00011/1, MC_UU_12013/2, MC_UU_00011/5] Funding Source: UKRI
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据