For example, Holstege et al.77 compared gene-based burden of rare damaging variants in exome sequencing data and observed significant associations of variants in ATP8B4 and ABCA1 with AD risk and a suggestive risk signal in ADAM10, in addition to confirming known rare variant burden signals for ABCA7, SORL1, and TREM2. Additionally, they were able to identify RIN3, CLU, ZCWPW1, and ACE as potential drivers of respective AD GWAS loci77. This evidence concerns the gene CLU and Alzheimer disease.