Missing heritability problem

The missing heritability problem^[1]^[2]^[3]^[4]^[5]^[6] refers to the difference between heritability estimates from genetic data and heritability estimates from twin and family data across many physical and mental traits, including 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, or the role of genes may have been severely overestimated.

^ 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. Bibcode:2009Natur.461..747M. doi:10.1038/nature08494. PMC 2831613. PMID 19812666.
^ 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. Bibcode:2012PNAS..109.1193Z. doi:10.1073/pnas.1119675109. PMC 3268279. PMID 22223662.
^ Lee, S. H.; Wray, N. R.; Goddard, M. E.; Visscher, P. M. (2011). "Estimating Missing Heritability for Disease from Genome-wide Association Studies". American Journal of Human Genetics. 88 (3): 294–305. doi:10.1016/j.ajhg.2011.02.002. PMC 3059431. PMID 21376301.
^ 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.
^ 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.
^ "Personal genomes: The case of the missing heritability", Maher 2008, Nature.

[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. Bibcode:2009Natur.461..747M. doi:10.1038/nature08494. PMC 2831613. PMID 19812666.

[zuk-2] 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. Bibcode:2012PNAS..109.1193Z. 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". American Journal of Human Genetics. 88 (3): 294–305. doi:10.1016/j.ajhg.2011.02.002. PMC 3059431. PMID 21376301.

[slatkin-4] 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.

[6] "Personal genomes: The case of the missing heritability", Maher 2008, Nature.

[1]

[2]

[3]

[4]

[5]

[6]