Polyunsaturated fatty acids and attention deficit hyperactivity disorder/autism spectrum disorder risk: a multivariable Mendelian randomization study

Abstract Purpose Attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are prevalent neurodevelopmental disorders caused by genetic and environmental factors. The basic brain processes or biomarkers of novel ADHD/ASD medication targets are yet unknown. Observational studies have linked polyunsaturated fatty acids (PUFAs) to ADHD/ASD, but the causative linkages are unknown. Methods A large genome-wide association study (GWAS) was pooled to give summary statistics on unsaturated fatty acids and ADHD/ASD utilizing a multivariate Mendelian randomization (MVMR) research design. DHA, LA, omega-3, and omega-6 fatty acids were examined in ADHD/ASD GWAS data. Inverse variance weighting (IVW) and MR-Egger and outlier point tests (MR-PRESSO) were used to evaluate data from univariate Mendelian randomization analysis of significant genetic connections with PUFA levels ( P < 5 × 10 -8 ). The odds ratio (OR) and 95% CI for MVMR analysis utilizing IVW were calculated using combinations of single nucleotide polymorphisms (SNPs) as a composite proxy for fatty acids. Results There was some degree of causality between genetically predicted LA and both susceptibilities (ADHD, OR = 0.898, 95% CI = 0.806–0.999, P = 0.049; ASD: OR = 2.399, 95% CI = 1.228–4.688, P = 0.010). However, other PUFAs were not associated with ADHD/ASD. Conclusion LA appears to be a substantial, independent cause of ADHD and ASD. LA may treat ADHD but worsen ASD. LA's function in ADHD and ASD needs additional longitudinal cohorts or randomized controlled studies.