Absence of Causal Relationship between Levels of Unsaturated Fatty Acids and Attention-Deficit/Hyperactivity Disorder: Evidence from Mendelian Randomization Study

Abstract

Objective Previous research suggests a potential link between unsaturated fatty acids (UFAs) and attention-deficit/hyperactivity disorder (ADHD), but the causal relationship remains uncertain. This study aims to investigate the causal association between ADHD and UFAs using Mendelian randomization (MR) analysis. Methods Summary data from genome-wide association studies were used to estimate UFAs levels, including Monounsaturated Fatty Acids (MUFAs), Polyunsaturated Fatty Acids (PUFAs), Omega-3 PUFAs, Omega-6 PUFAs, Linoleic Acid (LA), and Docosahexaenoic Acid (DHA), in a sample of 114,999 participants from the UK Biobank. Data from the Psychiatric Genomics Consortium, consisting of 38,691 individuals with ADHD and 186,843 controls, were used to examine the relationship between genetically predicted UFAs levels and ADHD. Various MR methods, including Inverse-variance weighted, MR Pleiotropy RESidual Sum and Outlier, MR-Egger, weighted median, and weighted mode, were employed to assess heterogeneity and pleiotropy. Results The Inverse-variance weighted method revealed only nominal evidence suggesting a potential causal relationship between genetically predicted PUFAs (OR = 0.92, 95% CI = 0.85-0.99, p = 0.031), Omega-6 PUFAs (OR = 0.90, 95% CI = 0.83-0.98, p = 0.020), and LA levels (OR = 0.90, 95% CI = 0.82-0.98, p = 0.021) with ADHD risk. However, after false discovery rate (FDR) correction, the p-values for PUFAs, Omega-6 PUFAs, and LA levels were 0.063, 0.062, and 0.062 respectively, which indicates that no effect of UFAs level on ADHD risk was found. Conclusion Our findings do not support a causal relationship between UFAs levels and ADHD, aligning with previous research results, suggesting that the use of UFAs supplements does not confer beneficial effects on ADHD symptoms.