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Chunk #27 — 4. DISCUSSION

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Nicotine dependence and comorbid psychiatric disorders: examination of specific genetic variants in the CHRNA5-A3-B4 nicotinic receptor genes.
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Next, we found no evidence to support a significant association between the risk diplotype in the CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster and any of the comorbid psychiatric disorders, and we demonstrated the sufficient power to detect associations of moderate effect sizes with an odds ratio range of 1.50-1.75. These null association results should be interpreted with caution as we had limited power to detect an effect size smaller than an odds ratio of 1.50. Modest genetic effects identified for common complex disorders can increase the risk by 1.3 or less. Overall, our findings indicate the genetic risk associated with the CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster is a robust specific risk factor for nicotine dependence, and not a shared risk with other comorbid psychiatric disorders. In other words, there is no support for pleiotropy.