Secondly, if common alleles have small genetic effects (low penetrance), but common disorders show heritability (inheritance in families), then multiple common alleles must influence disease susceptibility. For example, twin studies might estimate the heritability of a common disease to be 40%, that is, 40% of the total variance in disease risk is due to genetic factors. If the allele of a single SNP incurs only a small degree of disease risk, that SNP only explains a small proportion of the total variance due to genetic factors. As such, the total genetic risk due to common genetic variation must be spread across multiple genetic factors. These two points suggest that traditional family-based genetic studies are not likely to be successful for complex diseases, prompting a shift toward population-based studies.
