Genetic risk for trait aggression and alcohol use predict unique facets of alcohol-related aggression.

Spychala, Kellyn M.; Yeung, Ellen W.; Miller, Alex P.; Slutske, Wendy S.; ACTION Consortium,; Wilhelmsen, Kirk C.; Gizer, Ian R.

doi:10.1037/adb0001015

Cited by 1 publication

(1 citation statement)

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“…MR analyses were conducted using sets of GWAS summary statistics for aggression (n = 87,485; Ip et al, 2021), alcohol consumption (n = 403,931; obtained from direct-to-consumer genetics company 23andMe, Inc., Sunnyvale, CA and described in Liu et al, 2019), AUD (n = 514,944), ADHD (n= 225,534; Demontis et al, 2023), and EF (n = 427,037; Hatoum et al, 2023). For the AUD summary statistics, a metanalysis of separate summary statistics from the Psychiatric Genomics Consortium (Walters et al, 2018), Million Veterans Program (Zhou et al, 2020), and FinnGen (FinnGen, 2021) was conducted (Spychala et al, 2024). These GWAS summary statistics were chosen in order to avoid sample overlap, which can bias MR analyses.…”

Section: Methodsmentioning

confidence: 99%

Executive Function as an Underlying Mechanism of Alcohol Use, Aggression, and ADHD

Spychala,

Friedman,

Gizer

2024

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BackgroundExecutive functioning (EF) has been proposed as a transdiagnostic risk factor for externalizing disorders and behavior more broadly, including attention-deficit/hyperactivity disorder (ADHD), aggression, and alcohol use. Previous research has demonstrated both phenotypic and genetic overlap among these behaviors, but has yet to examine EF as a common causal mechanism. The current study examined reciprocal causal associations between EF and several externalizing behaviors using a Mendelian randomization (MR) approach.MethodsTwo-sample MR was conducted to test causal associations between EF and externalizing behaviors. Summary statistics from several genome-wide association studies (GWASs) were used in these analyses, including GWASs of EF, ADHD diagnostic status, drinks per week, aggressive behavior, and alcohol use disorder (AUD) diagnostic status. Multiple estimation methods were employed to account for horizontal pleiotropy (e.g., inverse variance weighted, MR-PRESSO, MR-MIX).ResultsEF demonstrated significant causal relationships with ADHD (P < 0.01), AUD (P < 0.03), and alcohol consumption (P < 0.01) across several estimation methods. Reciprocally, ADHD showed a significant causal influence on EF (P < 0.03). Nonetheless, caution should be used when interpreting these findings as there was some evidence for horizontal pleiotropy in the effect of EF on ADHD and significant heterogeneity in variant effects in the other relations tested. There were no significant findings for aggression.ConclusionsFindings suggest that EF may be a causal mechanism underlying some externalizing behaviors, including ADHD and alcohol use, and that ADHD may also lead to lower performance on EF tasks.

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