Missing heritability problem

The "missing heritability" problem[1][2][3][4][5] can be defined as the fact that individual genes cannot account for much of the heritability of diseases, behaviors, and other phenotypes. This is a problem that has significant implications for medicine, since a person's susceptibility to disease may depend more on "the combined effect of all the genes in the background than on the disease genes in the foreground".

A model has been introduced that takes into account epigenetic inheritance on the risk and recurrence risk of a complex disease.[4]

The limiting pathway (LP) model has been introduced in which a trait depends on the value of k inputs that can have rate limitations due to stoichiometric ratios, reactants required in a biochemical pathway, or proteins required for transcription of a gene. Each of these k inputs is a strictly additive trait that depends on a set of common or rare variants. When k = 1, the LP model is simply a standard additive trait.[2]

The missing heritability is only missing if the reason for the heritability of a trait across many cultures/ecologies or geographic regions is the same, that is, only if the same alleles are effecting the observed heritability. However high and however consistent the heritability the genes behind it (the genes effecting it) may vary with the population.

References

  1. ↑ Manolio, T. A.; Collins, F. S.; Cox, N. J.; Goldstein, D. B.; Hindorff, L. A.; Hunter, D. J.; McCarthy, M. I.; Ramos, E. M.; Cardon, L. R.; Chakravarti, A.; Cho, J. H.; Guttmacher, A. E.; Kong, A.; Kruglyak, L.; Mardis, E.; Rotimi, C. N.; Slatkin, M.; Valle, D.; Whittemore, A. S.; Boehnke, M.; Clark, A. G.; Eichler, E. E.; Gibson, G.; Haines, J. L.; MacKay, T. F. C.; McCarroll, S. A.; Visscher, P. M. (2009). "Finding the missing heritability of complex diseases". Nature 461 (7265): 747–753. doi:10.1038/nature08494. PMC 2831613. PMID 19812666.
  2. ↑ 2.0 2.1 Zuk, O.; Hechter, E.; Sunyaev, S. R.; Lander, E. S. (2012). "The mystery of missing heritability: Genetic interactions create phantom heritability". Proceedings of the National Academy of Sciences 109 (4): 1193–1198. doi:10.1073/pnas.1119675109. PMC 3268279. PMID 22223662.
  3. ↑ Lee, S. H.; Wray, N. R.; Goddard, M. E.; Visscher, P. M. (2011). "Estimating Missing Heritability for Disease from Genome-wide Association Studies". The American Journal of Human Genetics 88 (3): 294. doi:10.1016/j.ajhg.2011.02.002.
  4. ↑ 4.0 4.1 Slatkin, M. (2009). "Epigenetic Inheritance and the Missing Heritability Problem". Genetics 182 (3): 845–850. doi:10.1534/genetics.109.102798. PMC 2710163. PMID 19416939.
  5. ↑ Eichler, E. E.; Flint, J.; Gibson, G.; Kong, A.; Leal, S. M.; Moore, J. H.; Nadeau, J. H. (2010). "Missing heritability and strategies for finding the underlying causes of complex disease". Nature Reviews Genetics 11 (6): 446–450. doi:10.1038/nrg2809. PMC 2942068. PMID 20479774.