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==== Modeling the environment: MZ discordant designs ==== As MZ twins share both their genes and their family-level environmental factors, any differences between MZ twins reflect E: the unique environment. Researchers can use this information to understand the environment in powerful ways, allowing [[epidemiology|epidemiological]] tests of causality that are otherwise typically confounded by factors such as gene–environment covariance, [[reverse causation]] and [[confounding]]. An example of a positive MZ discordant effect is shown below on the left. The twin who scores higher on trait 1 also scores higher on trait 2. This is compatible with a "dose" of trait 1 causing an increase in trait 2. Of course, trait 2 might also be affecting trait 1. Disentangling these two possibilities requires a different design (see below for an example). A null result is incompatible with a causal hypothesis. {| | [[File:Twin Study MZ discordant positive example.png|thumb|left|A depiction of MZ-discordance data]] | [[File:Twin Study MZ discordant test of hypothesis that exercise protects against depression.png|thumb|MZ discordant test of hypothesis that exercise protects against depression]] |} Take for instance the case of an observed link between depression and exercise (See Figure above on right). People who are depressed also reporting doing little physical activity. One might ''hypothesise'' that this is a [[causal]] link: that "dosing" patients with exercise would raise their mood and protect against depression. The next figure shows what empirical tests of this hypothesis have found: a null result.<ref name="DeMoor2008">{{cite journal | last1 = De Moor | first1 = M. H. | last2 = Boomsma | first2 = D. I. | last3 = Stubbe | first3 = J. H. | last4 = Willemsen | first4 = G. | last5 = de Geus | first5 = E. J. | year = 2008 | title = Testing causality in the association between regular exercise and symptoms of anxiety and depression | doi = 10.1001/archpsyc.65.8.897 | journal = Archives of General Psychiatry | volume = 65 | issue = 8| pages = 897–905 | pmid=18678794| doi-access = free }}</ref> '''Longitudinal discordance designs''' [[File:Twin Study MZ discordant design.png|thumb|A cross-lagged longitudinal MZ discordant twin design. This model can take account of relationships among differences across traits at time one, and then examine the distinct hypotheses that increments in trait1 drive subsequent change in that trait in the future, or, importantly, in other traits.]] As may be seen in the next Figure, this design can be extended to multiple measurements, with consequent increase in the kinds of information that one can learn. This is called a cross-lagged model (multiple traits measured over more than one time).<ref name="Burt2009">{{cite journal | last1 = Burt | first1 = S. A. | last2 = McGue | first2 = M. | last3 = Iacono | first3 = W. G. | year = 2009 | title = Nonshared environmental mediation of the association between deviant peer affiliation and adolescent externalizing behaviors over time: results from a cross-lagged monozygotic twin differences design | doi = 10.1037/a0016687 | pmid = 19899929 | journal = Dev Psychol | volume = 45 | issue = 6| pages = 1752–60 | pmc = 2778800 }}</ref> In the longitudinal discordance model, differences between identical twins can be used to take account of relationships among differences across traits at time one (path A), and then examine the distinct hypotheses that increments in trait1 drive subsequent change in that trait in the future (paths B and E), or, importantly, in other traits (paths C & D). In the example, the hypothesis that the observed [[correlation]] where [[Depression (mood)|depressed]] persons often also [[exercise]] less than average is causal, can be tested. If exercise is protective against depression, then path D should be significant, with a twin who exercises more showing less depression as a consequence.
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