COIOS
Healthcare today Item refines preprint

APOE e4 dementia and liver associations differ by ancestry in 367,757 US adults

A phenome-wide study of APOE genotype in 367,757 All of Us participants found 27 associated phenotypes, with dementia risk largest in those of European ancestry and e4 protection against fatty liver disease present in East Asians but absent in African-ancestry participants.

Researchers tested APOE genotype, ordered by Alzheimer's risk, against 2,632 phenotypes in 367,757 All of Us participants across six genetic ancestry groups, and against plasma protein levels in 9,132. Twenty-seven phenotypes were associated, mainly neurological and lipid traits, and nine associations differed by ancestry. Five lipid traits showed larger effects in females, and plasma SNAP25 tracked e4 dosage across all ancestries.

Why it is interesting: Tests APOE genotype against 2,632 phenotypes across six ancestry groups, in a resource where earlier work was largely restricted to European-ancestry cohorts.

Source
medRxiv, 28 September 2026
DOI
10.64898/2026.09.26.26364080
Type
Preprint
Design
Phenome-wide association study of APOE genotype against 2,632 phenotypes in 367,757 All of Us participants across six ancestry groups, with plasma proteomics in 9,132
Verdict
Refines prior evidence
Driver
Dementia