B3242 - Identifying maternal and early infant biomarkers for Fetal Alcohol Spectrum Disorder - 24/01/2019
Fetal alcohol spectrum disorders (FASDs) are lifelong disabilities caused by prenatal alcohol exposure. FASD is thought to be the leading preventable cause of developmental disability in the world and is associated with mental health problems, antisocial behaviour and substance misuse. Understanding which individuals are most at risk to develop FASD is key as it has been shown that an early diagnosis or risk identification could help with primary and secondary prevention, as well as amelioration and treatment efforts. Early identification of individuals most at risk for FASD via the identification of robust maternal and infant biomarkers will offer an early window for intervention, will focus specialist diagnostic efforts in a resource-limited healthcare system, and will contribute towards mitigating FASD-related disabilities in later life. It may also prevent or reduce foetal exposure to alcohol in subsequent pregnancies.
This project will focus on early identification of FASD by DNA methylation levels, which are known to be altered by alcohol use. Indeed, a DNA methylation alcohol (DNAm-Alc) score, comprising 144 CpG sites, was recently developed by Liu et al. that can robustly distinguish between current heavy drinkers and non-drinkers in a general population. In addition, strong evidence from animal models indicates that alcohol use during pregnancy is capable of altering offspring DNAm.
McQuire et al. have developed an algorithm to identify individuals at high risk of FASD regardless of them having received a formal (and rare!) diagnosis. We propose to compare this algorithmic identification with DNAm-based markers to find out whether prenatal risk assessment would be possible.
References
Liu, C. et al. A DNA methylation biomarker of alcohol consumption. Mol. Psychiatry 23(2):422-433 (2018)
McQuire C, Mukherjee R, Hurt L, Higgins A, Greene G, Farewell D et al. Screening prevalence of fetal alcohol spectrum disorders in a region of the United Kingdom: A population-based birth-cohort study. Prev Med (Baltim) 2019; 118: 344â351.