missing heritability

Stringer S, Derks EM, Kahn RS, Hill WG & Wray NR 2013 Assumptions and properties of limiting pathway models for analysis of epistasis in complex traits. PLoS ONE 8:e68913.

• heritability estimates from family (including twin studies) are biased upwards
• Zuk et al. revisited overestimation of narrow sense heritability from twin studies as a result of confounding with non-additive genetic variance
• they conclude that over-estimation of narrow sense heritability from family data ('phantom heritability') may explain an important proportion of missing heritability
• for highly heritable quantitative traits large phantom heritability estimates from twin studies are possible only if a large contribution of common environment is assumed
• the LP model is underpinned by strong assumptions that are unlikely to hold, including that all contributing pathways have the same mean and variance and are uncorrelated
• in outbred populations the contribution of additive genetic variance is likely to be much more important than the contribution of non-additive variance