Personality traits like novelty seeking (NS), harm avoidance (HA), and reward dependence (RD) are known to be moderately heritable (30-60%). These personality traits and their comorbidities, such as alcohol dependence (AD), may share genetic components. We examined 11,120 single nucleotide polymorphisms (SNPs) genotyped in 292 nuclear families from the Genetic Analysis Workshop 14, a subset from the Collaborative Study on the Genetics of Alcoholism (COGA). A family-based association analysis was performed using the FBAT program. NS, HA, and RD were treated as quantitative traits and AD as a binary trait. Based on a multivariate association test of three quantitative traits in FBAT, we observed 20 SNPs with p < 10(-3). Interestingly, several genes (TESK2, TIPARP, THEMIS, ABLIM1, RFX4, STON2 and LILRA1) are associated with three personality traits with p < 10(-3) using single trait analysis and AD. Especially, SNP rs727532 within ABLIM1 gene at 10q25 showed the most significant association (p = 6.4 × 10(-5)) in the multivariate test and strong associations with NS, HA, RD, and AD (p = 4.48 × 10(-4), 1.2 × 10(-5), 5.6 × 10(-5), 3.12 × 10(-4), respectively) in the COGA sample. In addition, the association of rs727532 with AD was confirmed in a replication study. This study reports some newly recognized associations between several genetic loci and both AD and three personality traits.