Genotypes were determined for 739 dinucleotide microsatellite markers (14) on 158 pedigrees containing 611 individuals with an average of 3.87 individuals genotyped per family (these figures apply to the entire SMOFAM dataset). A sex-averaged genetic map developed by Applied Biosystems (Foster City, CA), using 763 autosomal map positions generated from CEPH genotype data, was used in the linkage analysis and all cM references herein are with respect to this map1. All available genotypes were analyzed for each family using PREST to validate the structure of pedigrees (23). Pedcheck was used to detect non-Mendelian inheritance patterns (24). The probability that each genotype was correct was assessed in the context of all other available genotypes using the error-checking algorithm implemented in Merlin (25). Less than 0.5% of all genotypes were excluded after these quality controls were applied. Autosomal multipoint non-parametric linkage analysis (NPL) was performed on the final genotype data in Merlin with the nicotine withdrawal sensitivity score as the phenotype (25–26). Merlin (25) was used to identify the number of times a LOD score as significant as the MLS observed in this linkage analysis was observed in 1,000 simulated genome scans.
