Massively parallel assessment of gene regulatory activity at human cortical-structure-associated variants.

Massively parallel reporter assay reveals 918 regulatory variants linked to human cortical structure, with over half showing allelic effects and some being condition-dependent.

• Why it matters: Understanding the functional impact of noncoding genetic variants is crucial for deciphering the genetic basis of cortical development and associated disorders, yet many variants' roles remain unknown.
• What they did: The study tested 9,092 cortical-structure-associated variants in human neural progenitor cells using a high-throughput reporter assay, both at baseline and during Wnt stimulation, identifying key regulatory variants.
• The result: Findings highlight the significant role of Alu elements in cortical expansion and suggest that spatial transcription factor expression influences regional effects of variants, advancing the understanding of genetic regulation in brain development.