Genetics and statistical genetics · BEGINNER LESSON
Missing heritability
Missing heritability is the gap between heritability estimated from family or twin studies and the smaller amount explained by genome-wide association studies (GWAS) or tested SNPs. It means that known genetic markers do not yet account for all the inherited variation suggested by other methods.
What it is
Heritability is a population statistic: it describes how much of the variation in a trait, such as disease risk or a biological measurement, is associated with genetic differences within a group. In this topic, the key comparison is between heritability estimated from family or twin data and the smaller amount explained by genome-wide association studies (GWAS), which test many common DNA markers called single nucleotide polymorphisms (SNPs). The unexplained difference is called missing heritability. [1,2]
[2] Heritability of Crohn's disease and ulcerative colitis - PMC - NIH [3] Natural variation suggests candidate genes underlying ... - NIH
How researchers measure it
GWAS scans the genome for statistical associations between SNPs and a phenotype, meaning an observed trait such as disease status, number of children, or telomere length. The heritability captured by these associations is often written as SNP heritability. Family and twin studies estimate a broader kind of heritability from resemblance among relatives, often using classical twin modeling or pedigree-based methods. In several examples, the GWAS estimate is much lower than the family-based estimate, which creates the missing heritability gap. [0,1,2]
[1] Estimation and mapping of the missing heritability of human phenotypes [2] Heritability of Crohn's disease and ulcerative colitis - PMC - NIH [3] Natural variation suggests candidate genes underlying ... - NIH
Why the gap exists
The sources describe several reasons the gap can remain. Some DNA changes are rare, or they are structural variants, and common SNPs do not tag them well. Other causes include non-additive genetic effects, such as interactions between variants, and shared environmental effects among relatives, which can make pedigree-based estimates look higher than the part due only to additive genetic effects. Linkage disequilibrium, the tendency for nearby variants to be inherited together, can also make it harder to identify the true causal variant from an association signal. [0,1,2]
[1] Estimation and mapping of the missing heritability of human phenotypes [2] Heritability of Crohn's disease and ulcerative colitis - PMC - NIH [3] Natural variation suggests candidate genes underlying ... - NIH
Limits of current estimates
The estimates are not complete. One study was restricted to people of European ancestry because other groups in the dataset were smaller, especially for rare-variant analysis. Another limitation noted in twin work was imperfect information on some molecular and early-life factors. The sources also show that larger GWAS and whole-genome sequencing can reduce, but not always erase, the gap. [0,1]
[1] Estimation and mapping of the missing heritability of human phenotypes [2] Heritability of Crohn's disease and ulcerative colitis - PMC - NIH
SEE THE IDEA
How missing heritability appears
Estimates broad inherited contribution from related individuals.
Tests SNPs for statistical association with a trait.
Share explained by tested additive SNP effects.
Gap between family-based estimates and GWAS-based estimates.
Family or twin studies often give a larger heritability estimate than GWAS; the difference is the missing heritability gap.
A simplified path from broad family-based estimates to the smaller SNP-based estimate, showing where the gap appears.
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Sources and further reading
This general lesson was generated from public source material. It explains a concept; it does not interpret a private paper or provide medical advice.