The recent explosion of genomic data has allowed systematic searches for “fairy godmother” mutations or genetic variants that confer disease resistance (Williams, 2016). For example, recent work screened genomic sequence data from >589,000 subjects to identify 13 subjects with Mendelian disease causing mutations but without apparent disease. Other work has concluded that roughly 5% of healthy adults carry mutations predicted to “cause” disease (Johnston et al., 2015) but that screening of cohorts is vastly underpowered to detect specific protective factors, whether genetic or environmental. Hence, investigators focused on specific diseases or mechanisms have relied on several different, and frequently ad hoc, approaches to identify resistance variants.
