Forty-six genotyped SNPs covering the OPRM1 genetic region in the SMOFAM sample were available for analysis (Figure 3). SNPs in intervening sequence 1 (IVS1) of OPRM1 and SNPs in IVS3 through IVS5 are in significant LD in this sample, where SNPs in IVS2 appear to be in LD with SNPs in either the 5’ or 3’ LD block (Figure 3). Because there was substantial pair-wise LD between adjacent markers and to reduce redundant multiple testing, a subset of 21 SNPs that captured 85% of all SNPs in the region (MAF ≥ 0.05) at r2 > 0.8 were selected (Figure 3). Three SNPs with minor allele frequencies < 0.05 (rs12210856, rs1799972, and rs9282819) and seven subjects with genotypes inconsistent with Mendelian inheritance were removed from the dataset prior to FBAT analyses. In this FBAT analysis, there were 172 pedigrees (N=419 subjects) with complete OPRM1 SNP genotypes and nicotine withdrawal sensitivity scores. Eight of eighteen SNPs evaluated for family based association with the nicotine withdrawal sensitivity score had global P-values of less than 0.05 (Table 2). All eight SNPs with P-values <
