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DAGLA has been implicated in neuropsychiatric disorders via two independent lines of evidence. A cross‑disorder GWAS meta‑analysis involving 284,023 cases and 508,515 controls identified a risk SNP in DAGLA, suggesting a role for this gene in the etiology of attention deficit‑hyperactivity disorder (PMID:37924773). Additionally, in a separate exome sequencing study of 128 sporadic ADHD families, a de novo missense variant, c.3049G>C (p.Asp1017His), was reported in a proband (PMID:28332277). Collectively, these data support a limited gene‑disease association for DAGLA with ADHD, although the lack of segregation data and the single reported variant underscore the need for further validation.
Functional studies of DAGLA, while not directly performed in ADHD cohorts, provide important context for its role in neurodevelopment. Experimental assays in a neuro‑ocular syndrome model have demonstrated that truncating variants in DAGLA lead to abnormal protein localization and suggest a potential dominant negative effect (PMID:35737950). Although these findings do not recapitulate the ADHD phenotype exactly, they reinforce the biological plausibility of DAGLA contributing to neuropsychiatric disease. Overall, the convergence of cross‑disorder genetic association and isolated de novo variant evidence offers a promising, albeit preliminary, framework for incorporating DAGLA into future diagnostic decision‑making and therapeutic research.
Gene–Disease AssociationLimitedA de novo missense variant was identified in a sporadic ADHD proband (PMID:28332277) and supported by a cross‑disorder GWAS meta‑analysis (PMID:37924773); however, the absence of extensive segregation data limits the overall confidence. Genetic EvidenceLimitedThe genetic evidence is primarily driven by a single reported de novo variant in DAGLA (c.3049G>C (p.Asp1017His)) in an ADHD proband, alongside supportive gene‑based association data; however, the lack of replication or segregation information restricts the score. Functional EvidenceLimitedFunctional studies demonstrate that DAGLA truncating variants can alter protein localization with potential dominant negative effects (PMID:35737950), but these experiments were performed in the context of neuro‑ocular syndrome, not ADHD, thus providing limited direct support for the ADHD association. |