Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, PO Box 70259, Lamb Hall, Johnson City, TN, 37614-1700, USA.
J Mol Neurosci. 2012 Feb;46(2):265-71. doi: 10.1007/s12031-011-9530-6. Epub 2011 May 6.
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.
人格特质，如寻求新奇（NS）、回避伤害（HA）和奖励依赖（RD），被认为具有中等程度的遗传性（30-60%）。这些人格特质及其共病，如酒精依赖（AD），可能具有共同的遗传成分。我们研究了来自遗传分析研讨会 14 的 292 个核心家庭中的 11120 个单核苷酸多态性（SNP），这些家庭是酒精遗传研究合作（COGA）的一个子集。使用 FBAT 程序进行了基于家庭的关联分析。NS、HA 和 RD 被视为定量性状，AD 为二项性状。基于 FBAT 中三个定量性状的多变量关联检验，我们观察到 20 个 SNP 的 p 值小于 10(-3)。有趣的是，使用单性状分析，几个基因（TESK2、TIPARP、THEMIS、ABLIM1、RFX4、STON2 和 LILRA1）与三个人格特质和 AD 相关，p 值小于 10(-3)。特别是，10q25 上 ABLIM1 基因内的 SNP rs727532 在多变量检验中表现出最显著的关联（p=6.4×10(-5)），并且与 NS、HA、RD 和 AD 也具有强烈的关联（p=4.48×10(-4)、1.2×10(-5)、5.6×10(-5)、3.12×10(-4)，分别），在 COGA 样本中。此外，rs727532 与 AD 的关联在一项复制研究中得到了证实。本研究报告了一些新识别的遗传位点与 AD 和三个人格特质之间的关联。
