New rare-variant findings include pLoF in TIMD4 → elevated triglycerides, TREM1 → umbilical hernia, and TMEM127 → dermatophytosis. For TIMD4, common variants near the locus were known for lipid traits; the rare-variant evidence adds a direction of effect.
Cross-biobank meta-analysis with UK Biobank (up to 786,871 participants, 222 phenotypes) identified 193 pLoF gene–phenotype associations not significant in either cohort alone, 22 with no prior literature evidence.
All of Us markedly boosts non-European representation. Nearly half of the significant signals are found only by meta-analysis. Effects are also consistent: across 140 burden associations marginally significant in ≥2 similarity groups, we saw zero opposite-direction effects