While risk and resistance are symmetric liability aspects, resistance factors are not necessarily the opposites or alternative variants of the risk factors. This differentiates resistance from a more narrow concept of protective factors, which are “opposite ends of the same continuum [as risk factors]” or, alternatively, moderate, mediate or buffer the effects of risk factors (Hawkins, Catalano, & Miller, 1992). Aggregation, and thus the probability of detection, of risk and resistance factors differ in different portions of the liability distribution (Fig. 1). These sets of factors are likely to partially overlap. An example could be a SNP allele conferring elevated risk and the alternative allele that may confer enhanced resistance. The alternative allele, however, may be neutral, i.e., of no discernible phenotypic effect on the background of all other factors, rather than protective. Analogously, a resistance-enhancing variant may exist and be detectable within high-resistance populations, while the alternative variant(s) is neutral: e.g., the ALDH2*2 allele (Goedde et al., 1983; Harada et al., 1981). The rest of ALDH2 variation only weakly, if at all, influences alcoholism risk (Macgregor et al., 2009).
