KCNK18 and migraine disorder: However, it may be less useful in the case of KCNK18 variants because a higher allele frequency may be anticipated for two reasons: (i) a complete loss of TRESK function has clearly been tolerated in this family without affecting survival or reproductive fitness, so deleterious TRESK variants will not be subject to negative selection pressures; and (ii) the lifetime migraine prevalence of 15% or more is such that if a KCNK18 mutation was associated with migraine, individuals with such a mutation will be in the ExAC cohort at higher frequencies than for other less prevalent disorders.