As the genotyping technology improved, candidate gene and genomewide association methods were developed as a means to identify genetic variants that confer increased risk for AD. However, due to the etiological complexity of complex traits like AD, newer DNA sequencing methods, in particular, next generation sequencing (NGS) have become increasingly necessary as they provide a more accurate description of both common and rare variants (i.e., be they single nucleotide polymorphisms (SNPs) or structural variants). Both linkage and association studies are heavily focused on genetic variation that can be captured by genomic platforms designed to identify rare and/or common variation within a specific gene or across the entire genome, usually by relying upon linkage disequilibrium (LD). However, both methods have significant differences that affect their interpretation. Linkage studies are often regarded as being more powerful than association studies because of their ability to capture variation attributable to rare variants; however, they lack specificity as they focus on identifying stretches of DNA that either contain or are linked to the gene/genes that underlie a trait. Linkage study findings may lead to gene
