The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism

Marui T, Funatogawa I, Koishi S, Yamamoto K, Matsumoto H, Hashimoto O, Jinde S, Nishida H, Sugiyama T, Kasai K, Watanabe K, Kano Y, Kato N. The NADH‐ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism. Objective: Autism appears to have a strong genetic component. The product of the NADH‐ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene is included in the mitochondrial electron transport chain. Method: We performed a case–control study of 235 patients with autism and 214 controls and examined three single‐nucleotide polymorphisms (SNPs) within this gene in a Japanese population. We then conducted a transmission disequilibrium test (TDT) analysis in 148 autistic trios. Results: In the case–control study, two SNPs (rs12666974 and rs3779262) showed a significant association with autism (P = 0.00064 and 0.00046 respectively). Furthermore, a haplotype containing these two SNPs showed a significant association (P‐global = 0.0013, individual haplotype A‐A: P = 0.010). In TDT analysis, the global and A‐A haplotype P‐values also indicated significant associations. Minor allele and genotype frequencies were decreased in the autistic subjects. Conclusion: We found significant association between the NDFA5 gene and autism.