Three legs of the missing heritability problem

Abstract

The so-called 'missing heritability problem' is often characterized by behavior geneticists as a numerical discrepancy between alternative kinds of heritability. For example, while 'traditional heritability' derived from twin and family studies indicates that approximately ∼50% of variation in intelligence is attributable to genetics, 'SNP heritability' derived from genome-wide association studies indicates that only ∼10% of variation in intelligence is attributable to genetics. This 40% gap in variance accounted for by alternative kinds of heritability is frequently referred to as what's "missing." Philosophers have picked up on this reading, suggesting that "dissolving" the missing heritability problem is merely a matter of closing the numerical gap between traditional and molecular kinds of heritability. We argue that this framing of the problem undervalues the severity of the many challenges to scientific understanding of the "heritability" of human behavior. On our view, resolving the numerical discrepancies between alternative kinds of heritability will do little to advance scientific explanation and understanding of behavior genetics. Thus, we propose a new conceptual framework of the missing heritability problem that comprises three independent methodological and explanatory challenges: the numerical gap, the prediction gap, and the mechanism gap.

Keywords: Behavior genetics; Explanation; Genomics; Heritability; Mechanism; Prediction.

Figure 1:. The Three Legs of the Missing Heritability Problem.

(A) The numerical gap regards the quantitative discrepancies that arise when different kinds of heritability are estimated for the same phenotype. GWAS Heritability is systematically lower than SNP heritability, which is systematically lower than traditional quantitative genetic heritability. For any given phenotype, the numerical gap would be closed if heritability derived from genomic data (h²_GWAS or h²_SNP) were approximately similar to heritability derived from twin and family studies (h²_TWIN). (B) The prediction gap regards the practical challenge of making accurate and reliable prediction of behavioral phenotypes from molecular genotypes (i.e., DNA). The dotted line represents a predictive relationship. For any given phenotype, the prediction gap would be closed if it were possible to make useful individual-level DNA-based prediction across most populations and environments. (C) The mechanism gap regards the methodological and explanatory challenges of identifying and detailing a causal-mechanical pathway from genotype to behavioral phenotype. The solid arrows represent causal relationships and the black box represents undiscovered mechanism(s). For any given phenotype, the mechanism gap would be closed if mechanism(s) or mechanistic information were identified and detailed for the genotype-phenotype pathway of investigative interest.