For replication of our GWAS findings, we used a family-based sample containing 402 nuclear families that included a total of 1,251 subjects (412 males and 839 females) (16). All the study subjects are of African-American (AA) origin and were recruited primarily from the Mid-South states of Tennessee, Mississippi, and Arkansas during 1999-2004. Proband smokers were required to be at least 21 years of age, have smoked for at least the last five years, and have consumed an average of 20 cigarettes per day for the last 12 months. Siblings and parents of a smoking proband were recruited whenever possible, regardless of their smoking status. Extensive data were collected on each participant, including demographics (e.g., sex, age, race, biological relationships, weight, height, years of education, and marital status), medical history, smoking history and current smoking behavior, ND, and personality traits assessed by various questionnaires, available at NIDA Genetics Consortium Website (http://zork.wustl.edu/nida). All participants provided informed consent. The study protocol and forms/procedures have been approved by all participating Institutional Review Boards.