This scheme depicts the risk spectrum predisposing to common diseases as one continuum, using AD as an example. The continuum extends from the most extreme genetic form (“Mendelian genes”; green) to cases influenced by genetic susceptibility factors (“Genetic risk factors”; orange), until reaching into a less well-defined area of cases that may be caused by genes of lesser penetrance/lower effect size and/or altogether nongenetic factors (“Nongenetic risk factors”; gray). Established Mendelian genes (APP, PSEN1, and PSEN2) or genetic risk factors (APOE-ε4) are represented by shaded boxes and represent the most obvious candidates of AD genetics; the width of these boxes approximately represents the relative contribution to the overall risk for disease. Black boxes indicate still-elusive disease genes/risk factors (“?”). Colored arrows indicate possible gene-gene and gene-environment interaction patterns: yellow arrows represent previously suggested interactions (e.g., between PSEN1 and APOE-ε4). Note that some interactions (red arrows) as well as the number of elusive genes are entirely hypothetical and are depicted for didactic purposes only.