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Chunk #25 — Discussion

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The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies.
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The extension and confirmation of the prior findings with respect to the effect of the 5HTTLPR on mRNA expression is gratifying and more effectively restrains the effect size of this polymorphism on gene transcription and perhaps, by extension, clinical effect. The effects of the s and l variants on mRNA expression have been examined in at least four prior investigations using a total of ~150 lymphoblast cell lines [Lesch et al., 1996; Hranilovic et al., 2004; Bradley et al., 2005]. Overall, the studies found that variance at the 5HTTLPR accounted for ~4–5% of the total variance in SLC6A4 mRNA production. The current study is very much consistent with those prior findings.