Omnigenic model

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The omnigenic model of the genetics of complex traits posits that human gene regulatory networks are so interconnected that thousands of individual genes contribute at least slightly to the phenotype through expression in relevant cells. Because it proposes that the genetic architecture of complex traits is affected by a large number of genes, it is similar to the infinitesimal model developed by Ronald Fisher. It also incorporates the concept of "universal pleiotropy", which states that genetic variation in one part of the genome can potentially have an indirect effect on any other trait.[1] The model was first proposed by Boyle et al. in a 2017 paper in Cell.[2][3][4] According to this model, a small number of "core genes" with biological relevance to a given trait, as well as their regulators and associated pathways, contribute to complex human traits. "Peripheral" genes are also said to far outnumber core genes for a trait, and to contribute to much more of its heritability, despite being outside of the key pathways associated with the trait.[5][6][7]

References

  1. ^ Timpson, Nicholas J.; Greenwood, Celia M. T.; Soranzo, Nicole; Lawson, Daniel J.; Richards, J. Brent (2017-12-11). "Genetic architecture: the shape of the genetic contribution to human traits and disease". Nature Reviews Genetics. 19 (2): 110–124. doi:10.1038/nrg.2017.101. hdl:1983/af2c1b78-3cca-42ab-b973-717e01938cc4. ISSN 1471-0056. PMID 29225335. S2CID 23280236.
  2. ^ Boyle, Evan A.; Li, Yang I.; Pritchard, Jonathan K. (June 2017). "An Expanded View of Complex Traits: From Polygenic to Omnigenic". Cell. 169 (7): 1177–1186. doi:10.1016/j.cell.2017.05.038. PMC 5536862. PMID 28622505.
  3. ^ Brown, Kristen V. (2017-06-16). "This Study is Forcing Scientists to Rethink the Human Genome". Gizmodo. Retrieved 2019-05-28.
  4. ^ Yong, Ed (2017-06-16). "What If (Almost) Every Gene Affects (Almost) Everything?". The Atlantic. Retrieved 2019-05-28.
  5. ^ Peedicayil, Jacob; Grayson, Dennis R. (April 2018). "An epigenetic basis for an omnigenic model of psychiatric disorders". Journal of Theoretical Biology. 443: 52–55. doi:10.1016/j.jtbi.2018.01.027. PMC 6512988. PMID 29378208.
  6. ^ van der Harst, Pim; Verweij, Niek (2018-02-02). "Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease". Circulation Research. 122 (3): 433–443. doi:10.1161/CIRCRESAHA.117.312086. ISSN 0009-7330. PMC 5805277. PMID 29212778.
  7. ^ Liu, Xuanyao; Li, Yang I.; Pritchard, Jonathan K. (May 2019). "Trans Effects on Gene Expression Can Drive Omnigenic Inheritance". Cell. 177 (4): 1022–1034.e6. doi:10.1016/j.cell.2019.04.014. PMC 6553491. PMID 31051098.