Editing Pleiotropy (section)

==Mechanism==
Pleiotropy describes the genetic effect of a single gene on multiple phenotypic traits. Recent genetic research distinguishes between three forms of pleiotropy: 

=== Biological pleiotropy ===
Biological pleiotropy also known as horizontal pleiotropy is when a causal variant or gene has direct and independent effects on more than one phenotypes. There are two sub- types og biological pleiotropy, single- gene pleiotropy and [[Gene family|multigene]] regulatory pleiotropy. 

==== Single- gene pleiotropy ====
Causal risk variants can affect several traits by acting on a single gene that has many different effects. There are several ways that this kind of gene pleiotropy can happen, and these possibilities can overlap. For example, a gene might have more than one molecular function, be involved in several separate biological pathways or cellular processes, or be active in different organs, tissues, or times and places in the body, each influencing different traits. Also, one gene can produce different versions of a protein, called [[Protein isoform|isoforms]], which vary in strucure and function and contribute to the gene's wide range of effects.<ref name=":1">{{Cite journal |last1=Lee |first1=Phil H |last2=Feng |first2=Yen- Chen A. |last3=Smoller |first3=Jordan W |date=Jan 1, 2021 |title=Pleiotropy and Cross-Disorder Genetics Among Psychiatric Disorders |url=https://www.biologicalpsychiatryjournal.com/article/S0006-3223(20)31987-9/abstract |journal=Biological Psychiatry |volume=89 |pages=20–31|doi=10.1016/j.biopsych.2020.09.026 |pmid=33131714 |pmc=7898275 }}</ref>

==== Multigene regulatory pleiotropy ====
Pleiotropy also occurs when a causal variant changes the expression of many genes. Every one of these genes may play a role in shaping different phenotypic outcomes. Regulatory pleiotropy can also arise from genetic influences on the 3D structure of chromosomes.<ref name=":1" />

=== Mediated pleiotropy ===
Also known as vertical pleiotropy and happens when a causal variant effect on one trait which itself causes effect on a different trait. An example of mediated pleiotropy is that gene variants that affect low-density lipoprotein (LDF) also affect coronary artery disease. <ref name=":1" />

=== Spurious pleiotropy ===
Sometimes, what looks like pleiotropy can be caused by problems in how the study is designed or how risk genes and traits are defined, leading to incorrect conclusions about pleiotropy. Spurious pleiotropy occures when there is a misclassification either at the genomic level or  the phenotypic level. At the genomic level, this might happen when a region of the [[genome]] linked to a special trait includes causal variants that are related. When this is the case, variants that influence different phenotypes through separate biological mechanisms may wrongly appear as a single pleiotropic locus. <ref name=":1" />

=== Other ===

==== Polygenicity- induced horizontal pleiotropy ====
There has been introduced a fourth type, polygenicity- induced horizontal pleiotropy, where several genetic loci with causal effects could be linked to multiple phenotypic traits. <ref name=":2">{{Cite journal |last=Fisch |first=Gene S. |date=2022-08-01 |title=Associating complex traits with genetic variants: polygenic risk scores, pleiotropy and endophenotypes |url=https://link.springer.com/article/10.1007/s10709-021-00138-2 |journal=Genetica |language=en |volume=150 |issue=3 |pages=183–197 |doi=10.1007/s10709-021-00138-2 |pmid=34677750 |issn=1573-6857|url-access=subscription }}</ref>

==== Network pleiotropy ====
Another model that has been proposed is network pleiotropy. In this model, a single causal variant influences several traits through one or more intermediate cell types within the same network. It may be especially useful for explaining multi-dimensional psyciatric disorders such as [[Schizophrenia|schizofrenia]] and [[bipolar disorder]].<ref name=":2" />