Title: Prenatal alcohol exposure, childhood development and teenage drinking: a study of trans-generational effects
Funder: Medical Research Council

Abstract: Aim To understand the mechanisms linking parental alcohol consumption with offspring alcohol consumption in order to develop appropriate preventive measures for problem adolescent drinking. Objectives 1. To determine whether maternal alcohol consumption in pregnancy has a biological effect on adolescent drinking behaviours and the onset of problem drinking, independent of family history of problem drinking, parental drinking during the offspring‘s childhood and adolescence and other components of shared environment such as socio-economic position and neighbourhood circumstances. 2. To use maternal genetic variants that are known to be robustly associated with alcohol consumption as instrumental variables for the causal effect of maternal alcohol consumption on offspring consumption, with control for the same variants in offspring. 3. To determine whether risk-factors for adolescent drinking such as school performance and peer group choice, which are often linked to more important outcomes in the domains of cognition and development, are mediators of the effect of prenatal alcohol exposure on adolescent drinking behaviours. 4. To determine whether prenatal alcohol exposure causes differences in methylation status of candidate genes associated with adolescent drinking and cognitive/developmental outcomes (epigenetic effect). 5. To determine whether paternal alcohol consumption pre-conception contributes to the adolescent alcohol phenotype and cognition/development, independently of intrauterine alcohol exposure and later drinking. 6. To study the association of prenatal alcohol exposure with cognitive and developmental outcomes using an instrumental variable approach and within-siblings comparisons, and to compare the results to those from a different population to strengthen their interpretation (UK Vs Norway). Methodology The Avon Longitudinal Study of Parents And Children -N=15000- and the Norwegian Mother and Child Cohort -N=100000- will provide data on parents (socio-demographic and lifestyle) and offspring (developmental and cognitive outcomes, adolescent drinking behaviour), collected prospectively since the index pregnancy. DNA banks exist for both studies. These will allow genotyping alcohol-related genetic variants, to be linked to offspring cognitive/behavioural/alcohol outcomes in instrumental variable analyses, and analysing offspring DNA methylation signatures. Relevant statistical methods - multivariable analysis, structural equation modelling, instrumental variables analysis - will be used as appropriate. Medical opportunities Understanding to what extent the association of maternal pregnancy alcohol intake with offspring initiation and amount of alcohol consumption is due to potentially irreversible intrauterine biological pathways, rather than shared familial lifestyles or shared genes, is important in order to determine strategies for the prevention of problem drinking in adolescents. This may be particularly important for female offspring, as their behaviour in pregnancy might affect their own offspring -an irreversible intrauterine effect could result in a trans-generational spiral.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE;CANCER AND NEOPLASMS;REPRODUCTIVE HEALTH AND CHILDBIRTH;CARDIOVASCULAR;ORAL AND GASTROINTESTINAL