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Chunk #35 — Discussion

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Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence.
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In this study, we used both ordinal phenotype (SI-2) and binary phenotype (SI-1) for smoking initiation. SI-2 is the modified SI-1 (never vs. others) considering the subcategories of “others.” Because the individuals in “former” group were those who smoked in the past but had stopped at the time of recruiting, we placed the “former smoker” between “never” and “occasional” smoker in the context of smoking initiation and current smoking interest. However, there would be an argument for the order of the ordinal phenotypes. Our previous candidate gene-based association study using the same ordinal phenotype definition has replicated the previously well-known smoking-related gene CHRAN5/A3/B5 (Li et al. 2010), which demonstrates the appropriateness of ordinal phenotype definition. In addition, the statistical test for checking the proportional odds assumption with respect to SNP variables showed that the proportionality assumption is reasonable.