Beyond exons: Linking noncoding heritability and polygenicity across complex human traits and disorders.

Exons contribute less to heritability as polygenicity increases, dropping from 22% in less-polygenic traits to 13% in highly polygenic traits.

• Why it matters: Understanding how genetic heritability is distributed across functional genome regions helps clarify the biological mechanisms underlying complex traits and disorders, which remains poorly characterized.
• What they did: Using a MiXeR-based framework, the study analyzed heritability across 74 functional annotations for 34 traits, introducing a likelihood-based score to quantify annotation-specific impacts.
• The result: Findings reveal a shift from gene-proximal regulatory architectures in less-polygenic traits to dispersed regulatory effects in highly polygenic traits, informing models of genetic architecture and trait heritability.