Three Legs of the Missing Heritability Problem

In 2008 Maher coined ‘the missing heritability problem’ (MHP), an issue about conflicting results from classical, ‘quantitative’ genetics and molecular genetics. For any trait, decades of classical genetics had... [ view full abstract ]

In 2008 Maher coined ‘the missing heritability problem’ (MHP), an issue about conflicting results from classical, ‘quantitative’ genetics and molecular genetics. For any trait, decades of classical genetics had inspired optimism that molecular investigations would lead to the discovery of single genes of large effect for nearly all behavioral traits, but to date none have been found. A second aspect of the MHP was the expectation that molecular genetic information would confer newfound genomic predictive ability -- still not true, as the best way to predict one’s height or IQ is to average that of their parents. A variety of explanations for missing heritability are now on offer; nearly all of them focus on closing the gap between quantitative and molecular estimates of heritability, which we call the heritability gap. Although we acknowledge the importance of reconciling conflicting heritability estimates, here we argue that the hunt for heritability overlooks the real problem of heritability, as it is only the first leg of a tripartite problem. In addition to the heritability gap, there is the challenge of accurately predicting phenotype from genotype, which we call the prediction gap. The third leg of the MHP is the mechanism gap, which involves elucidating meaningful causal-mechanical stories that link small genotypic differences (e.g., SNPs) to complex behavioral differences. The MHP remains alive and well until the three legs are resolved for any given behavioral trait.