Basic Research in Personality: Molecular Genetics of Personality

5-羟色胺转运体基因的变异体和NEO-PI-R神经质：在BLSA和SardiNIA样本中没有关联。美国医学遗传学B神经精神病学遗传学杂志，10.1002/ajmg.b.30932 5-羟色胺转运体基因启动子区（5-HTTLPR）的多态性是迄今为止研究最多的变体，被假设影响神经质、抑郁和焦虑相关的人格特征。以前的研究结果是混合的，并出现温和的性格问卷。使用TCI评估伤害避免或EPQ评估神经质的研究发现与5-HTTLPR无关。然而，使用NEO-PI-R或相关工具（NEO-PI，NEO-FFI）来测量神经质的研究发现了一些相关的证据。本研究检查了来自撒丁岛（意大利）内遗传隔离人群的样本中5-羟色胺转运蛋白基因变异的相关性，该样本比之前使用NEO-PI-R的样本（N = 3，913）大几倍。还在来自巴尔的摩老龄化纵向研究（BLSA）的样本（N = 548）中测试了这种关联，其中获得了重复的NEO-PI-R评估。 在SardiNIA样本中，我们发现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，冲动和脆弱性）没有显着关联。在BLSA样本中，我们发现杂合子组的神经质特征得分较低，这与以前的研究不一致。 我们还检查了SardiNIA中的8个SNP（N = 3，972）和BLSA中的9个SNP（N = 1，182），这些SNP位于5-羟色胺转运蛋白基因（SLC 6A 4）内或附近，未发现相关性。沿着其他大型研究，使用不同的表型措施，并没有发现任何关联，这项研究大大增加了对5-HTT变异和神经症相关性状之间的联系的证据。 从5-HTTLPR对焦虑相关性状的主要影响的第一份报告开始，大量研究已经在临床样本、神经影像学研究以及基因-基因和基因-环境相互作用研究中探索了该变体的相关性。大多数这些研究都是基于小样本，从这些文献的结果通常是混合的。考虑到当前和另外两项大规模研究的结果，这些研究拒绝了5-HTTLPR对神经症相关表型的主要影响，在解释小样本量研究的结果时需要更加谨慎，这些研究检查了复杂的表型（例如，杏仁核反应性或对SSRIs的反应）或复杂的相互作用。

Variants of the serotonin transporter gene and NEO-PI-R Neuroticism: No association in the BLSA and SardiNIA samples. Am J Med Genet B Neuropsychiatr Genet, 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, depression, and anxiety-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. From the first report of a main effect of the 5-HTTLPR on anxiety-related traits, a large number of studies have explored the association of this variant in clinical samples, in neuroimaging studies, and in gene-gene and gene-environment interaction studies. Most of these studies are based on small samples, and the results from this literature are generally mixed. Considering the results of the current and two other large scale studies that reject a main effect of the 5-HTTLPR on Neuroticism-related phenotypes, even greater caution is required in interpreting the results of studies with small sample sizes that examined complex phenotypes (e.g., amygdala reactivity or response to SSRIs) or complex interactions.