Spatial Distribution of Rare Missense Variants Within Protein Structures is Associated with AD Risk

Despite large genome‐wide association studies, only ∼30% of the heritability of Alzheimer’s disease is explained. The Alzheimer’s Disease Sequencing Project Whole Exome Sequencing (ADSP WES) has identified millions of genetic variants, over 97% of which are rare (MAF<1%), with 23% appearing in only one person. These rare variants could provide valuable information about new and previously identified risk loci for AD. However, current analysis strategies do not have power to detect associations for such rare variants.