For studies that do not meet any of the above criteria, an appealing approach is to use mixed models with PC covariates. In family-based studies in which the within-family component contributes much of the overall statistical power, the approach of ref. 30 may also prove useful. In data sets that do not contain family structure or cryptic relatedness, simpler association tests (with or without PC correction, based on above criteria) will probably be sufficient21, 23.