Several intriguing trends were evident in these data on human diseases. First, with few exceptions (e.g., Alzheimer’s disease and APOE), the regions implicated by GWAS were not previously known. Candidate genes based on prior knowledge of pathophysiology or intuition have usually not been identified. Second, the majority of these findings (90%) were not in the coding region of a gene, and only 8% were non-synonymous variants (i.e., DNA variants that change the amino acid sequence of the corresponding protein). Indeed, 43% were not in a known gene and 23% were not within 20,000 bases of a known gene. Common variation underlying complex human diseases is dissimilar to that underlying Mendelian diseases where major changes to proteins are typical.
