African origin haplotype protective for Alzheimer's disease in <i>APOE</i>ε4 carriers: exploring potential mechanisms.

ABSTRACT: APOEε4 is the strongest genetic risk factor for Alzheimer's disease (AD) with approximately 50% of AD patients carrying at least one APOEε4 allele. Our group identified a protective interaction between APOEε4 with the African-specific A allele of rs10423769, which reduces the AD risk effect of APOEε4 homozygotes by approximately 75%. The protective variant lies 2Mb from APOE in a region of segmental duplications (SD) of chromosome 19 containing a cluster of pregnancy specific beta-1 glycoprotein genes (PSGs) and a long non-coding RNA. Using both short and long read sequencing, we demonstrate that rs10423769_A allele lies within a unique single haplotype inside this region of segmental duplication. We identified the protective haplotype in all Afric

SUBMITTER: Bertholim-Nasciben L 

PROVIDER: S-EPMC11527192 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature