Download Elements of a Solid GxE Study

Elements of a Solid GxE Study
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a.hideLink:hover { border-bottom: 1px dotted #36f; } The problem of major
depression
In 2003, Caspi and colleagues tested the hypothesis that variation in the 5-HTTLPR gene could
be one factor in the observed differences in the effect of stressful life events on depression
outcomes. Using standard regression techniques, the authors reported that individuals with 1 or
2 copies of a 'shortallele
' (s-allele) exhibited more depressive symptoms, diagnosable depression, and suicidal ideation
following stressful life events than individuals with 2 copies of a 'long-allele' (l-allele). The
authors cautiously posited that these results could have implications not only for the treatment
and prevention of depression, but also for approaches to psychiatric research in general.
Read the abstract from the original study by Caspi et al 2003>> >
The elements of a solid GxE study design
The study by Caspi and colleagues (2003) was lauded not only for its novel approach, but also
for its solid design. It included:
- Selection of both gene and environmental variables with plausible interactive biologic
pathways
- Selection of environmental variable with known association with the phenotype
- Prospective and retrospective measurement of the environmental risk factor
- Accepted and validated measures of the phenotype, based on DSM-IV criteria
- Systematic examination of the specificity of the gene
Problems with replication
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Elements of a Solid GxE Study
There have been over 30 published attempts at replicating the observations of Caspi et al often
resulting in a mixed pattern of findings.
Reflect and Brainstorm
What factors do you think might be responsible for the lack of replication?
View some possibilities>>
An important observation to come from the multiple attempts at replication is that not every
study is well suited to testing gene-environment interactions. In particular, interaction studies
depend upon:
- Optimal study design
- Accurate and precise assessment of genetic and environmental factors
- Efficient statistical analysis
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In the next section we discuss general considerations in G x E study design, and review how
these issues may have impacted both the original and follow-up studies of stress and
5-HTTLPR interactions in major depression.
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