The selection of the OPRM1 gene for study is a limitation as there are other candidate genes located at chr6q25.2-q27 that may also contribute to the nicotine withdrawal sensitivity score phenotype. While the map location of OPRM1 is within the proximal region of the 2 lod support interval, OPRM1 is only one of several candidate genes potentially influencing the nicotine withdrawal sensitivity score trait located in the interval. Other candidate genes for future investigation in the 2 LOD support interval include the SLC22A1, SLC22A2 and SLC22A3 genes coding for the organic cation transporters that are responsible for cellular uptake of endogenous neurotransmitters such as acetylcholine and monamines, as well as xenobiotics.