Alcohol use and cognitive functioning in young adults: improving causal inference

Abstract

Background and Aims: There have been few longitudinal studies of association between alcohol use and cognitive functioning in young people. We aimed to examine whether alcohol use is a causal risk factor for deficient cognitive functioning in young adults. Design: Linear regression was used to examine the relationship between longitudinal latent class patterns of binge drinking and subsequent cognitive functioning. Two-sample Mendelian randomisation (MR) tested evidence for the causal relationship between alcohol use and cognitive functioning. Setting: South West England. Participants: The observational study included 3,155 adolescents and their parents (fully adjusted models) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Genetic instruments for alcohol use were based on almost 1,000,000 individuals from the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN). Genome-wide association studies for cognitive outcomes were based on 2,500 individuals from ALSPAC. Measurements: Binge drinking was assessed at approximately 16, 17, 18, 21, and 23 years. Cognitive functioning comprised working memory, response inhibition, and emotion recognition assessed at 24 years of age. Ninety-nine independent genome-wide significant SNPs associated with number of drinks per week were used as the genetic instrument for alcohol consumption. Potential confounders were included in the observational analyses. Findings: Four binge drinking classes were identified: low-risk (41%), early-onset monthly (19%), adult frequent (23%), and early-onset frequent (17%). The association between early-onset frequent binge drinking and cognitive functioning: working memory (b=0.09, 95%CI=-0.10 to 0.28), response inhibition (b=0.70, 95%CI=-10.55 to 11.95), and emotion recognition (b=0.01, 95%CI=-0.01 to 0.02) in comparison to low-risk drinkers were inconclusive as to whether a difference was present. Two-sample MR analyses similarly provided little evidence that alcohol use is associated with deficits in working memory using the inverse variance weight (b=0.29, 95%CI=-0.42 to 0.99), response inhibition (b=-0.32, 95%CI=-1.04 to 0.39), and emotion recognition (b=0.03, 95%CI=-0.55 to 0.61). Conclusions: Binge drinking in adolescence and early adulthood may not be causally related to deficiencies in working memory, response inhibition, or emotion recognition in youths.

Examining the bidirectional association between emotion recognition and autistic traits using observational and genetic analyses

“…It would be useful to investigate this further, potentially with Mendelian randomisation type or genomic structural equation modelling (Grotzinger et al, 2019) approaches, but the current GWAS for emotion recognition are underpowered to do this. We were also unable to examine the association between emotion recognition polygenic risk scores and autistic traits due to sample overlap with the GWAS for the DANVA (Coleman et al, 2017) and ERT (Mahedy et al, 2019) also being conducted in ALSPAC. To investigate whether our findings could be a result of shared genetic aetiology we looked at genetic correlations between these outcomes.…”

Association between inflammation and cognition: triangulation of evidence using a population-based cohort and Mendelian randomization analyses

“…The GWAS listed in Table 1 were used to identify genetic variants (Single Nucleotide Polymorphisms; SNPs) associated with inflammation (CRP, IL-6, sIL6R and GlycA) and cognition (working memory, emotion recognition, response inhibition) (Ahluwalia et al, 2021; Han et al, 2020; Kettunen et al, 2016; Ligthart et al, 2018; Mahedy et al, 2021; Rosa et al, 2019; Sarwar et al, 2012; Swerdlow et al, 2012). For details on GWAS (including any overlap with ALSPAC) and accessing data, see Supplementary Tables S8 and S10.…”

Drinking habits and executive functioning: a propensity score-weighted analysis of 78,832 adults

“…First, abundant evidence shows that patients with a diagnosis of alcohol use disorder exhibit deficits on a range of executive tasks [11]. Second, among adolescents and students, heavy social drinking or binge-drinking is typically not found to result in poorer executive functioning [12]- [16]. It has been suggested that compensatory mechanisms may dissipate negative effects of repeated alcohol intoxication on the developing brain [17], or that detrimental effects may appear at later age as a result of cumulative exposure [18].…”