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.
• What they did: Using a MiXeR-based framework, the study analyzed 74 functional annotations across 34 traits, introducing a likelihood-based score to quantify annotation-specific heritability contributions.
• The result: Findings suggest that as traits become more polygenic, heritability shifts from gene-proximal regulatory regions to dispersed regulatory architectures, informing models of genetic influence.