However, most of these identified signals are in noncoding regions and are in complex linkage disequilibrium (LD) with other variants, including the SNPs encoding the protein isoforms of APOE. Although we suspect the existence of additional variants modulating the risk of APOE isoforms, the complexities within the locus might present difficulties in elucidating their potential modulation of AD-related risk alleles. Here, APOE is linked to Alzheimer disease.