50 whys to look for genes: 35. Find “missing heritability”

[G]enomic studies have had difficulty identifying causally relevant genetic variants behind variation in human traits (McCarthy et al. 2008, Couzin-Frankel 2010). Even when many genetic variants are examined together, only a small fraction of the variation in the trait is associated with—or in statistical terms, “accounted for” by—the genetic variants. This finding has led to discussions about missing heritability (e.g., Manolio et al. 2009)…

and bridging the gap by finding additional genetic variants (e.g., Wheeler and Barroso 2012).

Complications

The expectation that genetic variants could account for a larger fraction of trait variation follows from ambiguous descriptions of heritability as… the “fraction of the variance of a phenotypic trait in a given population caused by (or attributable to) genetic differences” (Layzer 1974, 1259).  However, the heritability of classical heritability studies (which is Layzer’s focus) has no empirical or conceptual relationship to assessing the fraction of the variation in the trait is associated with—or in statistical terms, “accounted for” by—the genetic variants (see earlier post, Heritability, a technical term, can be visualized by non-specialists). Researchers are free to search for additional genetic variants associated with a disease, but there is no missing heritability that provides a warrant for their work.

References

The quote above is from page 124 in Taylor, Peter J. (2014) Nature-Nurture? No: Moving the Sciences of Variation and Heredity Beyond the Gaps.

Couzin-Frankel, J. (2010). “Major heart disease genes prove elusive.” Science 328(5983): 1220-1221.
Layzer, D. (1974). “Heritability analyses of IQ scores: Science or numerology?” Science 183(4131): 1259 – 1266.
Manolio, T. A., Collins, F. S., et al. (2009). “Finding the missing heritability of complex diseases.” Nature, 461: 747-753.
McCarthy, M. I., G. R. Abecasis, et al. (2008). “Genome-wide association studies for complex traits: consensus, uncertainty and challenges.” Nature Reviews Genetics 9(May): 356-369.
Wheeler, E. and I. Barroso (2011). “Genome-wide association studies and type 2 diabetes.” Briefings in Functional Genomics 10 (2): 52-60.
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(Introduction to this series of posts)

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