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Chunk #19 — DISCUSSION

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Nicotine withdrawal sensitivity, linkage to chr6q26, and association of OPRM1 SNPs in the SMOking in FAMilies (SMOFAM) sample.
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Our linkage analyses identified a MLS of 3.15 at 164.5 cM on chr6q26 for the nicotine withdrawal sensitivity score. Swan et al previously found a MLS of 2.7 at 159 cM on chr6q26 for withdrawal severity (the summation of nine withdrawal symptom scores, rated on a 4-point scale; 0, not at all to 3, severe, with range 0 to 27) in the SMOFAM sample (14). The use of the Rasch modeled nicotine withdrawal sensitivity score constructed from eight nicotine withdrawal symptoms as the phenotype in the present analysis resulted in an increase in the multipoint MLS of 0.45 units over the use of the sum of nine withdrawal symptoms as the phenotype in the previous analysis (14). This suggests that the use of the Rasch model using eight withdrawal symptoms may be a more precise measure of a nicotine withdrawal trait linked to chr6q26. The multipoint P and the empirical P suggest that a linkage analysis result of this magnitude is expected by chance approximately 5% of the time in this sample (44). Existing linkage studies using nicotine withdrawal symptoms