Quantifying heritability in functional regions of the coding and non-coding genome across diverse individuals

Rare variants with minor allele frequency <0.01 explain 30.6–67.7% of whole-genome heritability (h2WGS) for seven complex traits in 198,931 unrelated individuals.

• Why it matters: Heritability estimates have often relied on common variants and underrepresented non-European or admixed groups, leaving uncertainty about how rare and non-coding variation contributes.
• What they did: The authors estimated h2WGS using 73,600,953 autosomal and chromosome X variants across three genetic similarity groups, adjusting for population stratification and using simulations to assess inflation from linkage to missing or lower-quality variants.
• The result: After confounder adjustment, heritability enrichment was substantial in non-coding RNA exons (FE=8.7, P=3.56e-7), UTRs (FE=23.0, P=3.46e-30), distal regulatory regions (FE=33.8, P=3.26e-42), and protein-coding exons (FE=58.0, P=7.78e-15).

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