Shared genetic and molecular architecture between neurodevelopmental disorders and type 1 diabetes

Abstract

Epidemiological and clinical studies have suggested possible associations between type 1 diabetes (T1D) and neurodevelopmental disorders (NDDs), but these relationships remain inconsistent across disorders and populations. To clarify whether such mixed findings, we investigated the genetic architecture linking T1D with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), obsessive‐compulsive disorder (OCD), Tourette syndrome (TS), and anorexia nervosa (AN) using genome‐wide association study summary statistics. Global genetic correlations were estimated using linkage disequilibrium score regression, and local genetic correlations across 1703 genomic regions were assessed using ρ‐HESS. Shared genes and pathways were further explored. Global analysis showed limited overall genetic overlap, with a significant negative correlation observed only between ASD and T1D ( p  = 0.03). In contrast, local analysis identified 61 genomic regions with significant local genetic correlations between T1D and four disorders, with both positive and negative effect directions. Gene mapping identified two cross‐phenotype candidate genes, ERBB3 shared between ADHD and T1D and GABBR1 shared between ASD and T1D. ERBB3 localized to a region with significant local genetic correlation between ADHD and T1D, and pathway analysis highlighted MAPK signaling as a potential shared mechanism. These findings support limited global but locus‐specific shared genetic architecture between T1D and NDD traits.