An obvious but sometimes overlooked element in deciding whether or not to pursue any genetic association study is to weigh up all evidence of familial aggregation studies that have investigated the HERITABILITY of the disease of interest. Heritability is assessed through studying disease patterns among family members, in particular comparing monozygotic (MZ) with dizygotic (DZ) twins. Increased concordance of disease status among MZ vs. DZ twins suggests a role for genetic factors, since DZ twins share, on average, half their genes whilst MZ twins are genetically identical. Diseases of low heritability (e.g. 10-20%) will likely need very large sample sizes to allow the finding of aetiological genetic variants, which will need to be considered. More importantly, if good evidence exists that the heritability of the phenotype in question is (close to) zero, little will be gained from conducting a genetic case-control study.
