National Institute on Aging, NIH, DHHS, Baltimore, Maryland 21224, USA.
Am J Med Genet B Neuropsychiatr Genet. 2009 Dec 5;150B(8):1070-7. doi: 10.1002/ajmg.b.30932.
The polymorphism in the serotonin transporter gene promoter region (5-HTTLPR) is by far the most studied variant hypothesized to influence Neuroticism-related personality traits. The results of previous studies have been mixed and appear moderated by the personality questionnaire used. Studies that used the TCI to assess Harm Avoidance or the EPQ to assess Neuroticism have found no association with the 5-HTTLPR. However, studies that used the NEO-PI-R or related instruments (NEO-PI, NEO-FFI) to measure Neuroticism have found some evidence of association. This study examines the association of variants in the serotonin transporter gene in a sample from a genetically isolated population within Sardinia (Italy) that is several times larger than previous samples that used the NEO-PI-R (N = 3,913). The association was also tested in a sample (N = 548) from the Baltimore Longitudinal Study of Aging (BLSA), in which repeated NEO-PI-R assessments were obtained. In the SardiNIA sample, we found no significant association of the 5-HTTLPR genotypes with Neuroticism or its facets (Anxiety, Angry-Hostility, Depression, Self-Consciousness, Impulsiveness, and Vulnerability). In the BLSA sample, we found lower scores on Neuroticism traits for the heterozygous group, which is inconsistent with previous studies. We also examined eight SNPs in the SardiNIA (N = 3,972) and nine SNPs in the BLSA (N = 1,182) that map within or near the serotonin transporter gene (SLC6A4), and found no association. Along with other large studies that used different phenotypic measures and found no association, this study substantially increases the evidence against a link between 5-HTT variants and Neuroticism-related traits.
5-羟色胺转运体基因启动子区域（5-HTTLPR）的多态性是迄今为止研究最多的假设影响神经质相关人格特质的变体。先前研究的结果喜忧参半，似乎受到所使用的人格问卷的调节。使用 TCI 评估回避危害或 EPQ 评估神经质的研究未发现与 5-HTTLPR 相关。然而，使用 NEO-PI-R 或相关工具（NEO-PI、NEO-FFI）测量神经质的研究发现了一些关联的证据。本研究在一个来自意大利撒丁岛的遗传隔离人群（N=3913）中，对 5-羟色胺转运体基因的变体与神经质进行了关联研究。该关联还在巴尔的摩纵向老龄化研究（BLSA）的样本中进行了测试（N=548），其中获得了重复的 NEO-PI-R 评估。在 SardiNIA 样本中，我们没有发现 5-HTTLPR 基因型与神经质或其方面（焦虑、愤怒敌意、抑郁、自我意识、冲动和脆弱）之间存在显著关联。在 BLSA 样本中，我们发现杂合子组的神经质特征得分较低，这与之前的研究不一致。我们还检查了 SardiNIA 中的 8 个 SNP（N=3972）和 BLSA 中的 9 个 SNP（N=1182），这些 SNP 位于或靠近 5-羟色胺转运体基因（SLC6A4）内或附近，未发现关联。与其他使用不同表型测量方法且未发现关联的大型研究一起，本研究大大增加了 5-HTT 变体与神经质相关特征之间没有关联的证据。
