The following is a summary of “Relationship between autism and brain cortex surface area: genetic correlation and a two-sample Mendelian randomization study,” published in the January 2024 issue of Psychiatry by Li et al.

While brain surface area (SA) in autism spectrum disorder (ASD) shows regional alterations, its genetic link to ASD remains enigmatic.

Researchers conducted a retrospective study to assess the genetic correlation and causal impact of ASD on cortical SA.

They obtained data from genome-wide association studies (GWAS) conducted by the Psychiatric Genomics Consortium (18,381 ASD cases, 27,969 controls) and the Enhancing Neuroimaging Genetics through Meta-Analysis Consortium (33,992 European participants). Heritability for each trait was calculated using Linkage disequilibrium score regression (LDSC) and Heritability Estimation from Summary Statistics (HESS). To assess the genetic correlation between ASD and SA, LDSC determined a global correlation, while HESS examined local genetic covariance. Causal relationships were evaluated using three Mendelian randomization (MR) methods: Inverse-variance weighted, MR-Egger, and weighted median.

The result showed that LDSC identified a nominally significant genetic correlation (rg = 0.1229, P-value= 0.0346) between ASD and the SA of the rostral anterior cingulate gyrus, while HESS analysis did not reveal significant loci with genetic covariance. MR results indicated statistically significant estimates in the postcentral cortex (β (SE) = 21.82 (7.84) mm, 95% CI: 6.46 to 37.19 mm, P_IVW= 5.38 × 10^{− 3}, P_FDR= 3.09 × 10^-2), posterior cingulate gyrus (β (SE) = 6.23 (2.69) mm, 95% CI: 0.96 to 11.49 mm, P_IVW= 2.05 × 10^-2,P_FDR= 4.26 × 10^-2), and supramarginal gyrus (β (SE) = 19.25 (8.43) mm, 95% CI: 29.29 to 35.77 mm, P_IVW= 2.24 × 10^-2, P_FDR= 4.31 × 10^-2).

Investigators concluded that identified genetic underpinnings for altered cortical surface area in specific regions, advancing the understanding of ASD’s neuroanatomical basis.

Source: bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-024-05514-8