One AD-relevant fine-mapped variant is a large deletion in HP (chr16:72057133–72058849; 1,716 bp deletion), which spans two exons and results in a different protein isoform: a dimeric form (HP1) when both exons are deleted, showing reduced binding affinity to APOE and hemoglobin (Boettger et al. 2016), in contrast to the tetrameric form when no deletion is present, or the trimeric form when only one allele is affected. Here, APOE is linked to Alzheimer disease.