Willis-Owen Saffron A G, Turri Maria G, Munafò Marcus R, Surtees Paul G, Wainwright Nick W J, Brixey Richard D, Flint Jonathan
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Biol Psychiatry. 2005 Sep 15;58(6):451-6. doi: 10.1016/j.biopsych.2005.04.050. Epub 2005 Jul 14.
A promoter-based length polymorphism (5-HTTLPR) of the human serotonin gene (SLC6A4) has exhibited inconsistent association with emotionality phenotypes, such as major depression (MD) and the personality trait neuroticism (N). Several explanations have been posited to account for this discrepancy, including underpowered experimental design and variation in gender ratio, age, and ethnicity.
Here, we describe three independent tests of association between the 5-HTTLPR locus and both N and MD in samples selected for extremeness of N-score from two homogenous populations (n = 88,142, and 20,921). Calculations of statistical power indicated that at a 5% alpha level, these samples retain 100% power to detect a genetic effect accounting for just .5% of phenotypic variance. Effects of age were regressed out of the phenotypic measure, and gender was included as a covariate.
No statistically significant effects of genotype could be identified on either N or MD phenotypes (in all cases, p > or = .26), independently of the genetic mode of action applied.
Our data do not support the hypothesis that the 5-HTTLPR variant contributes significantly toward human emotionality as indexed by either the Eysenck Personality Questionnaire N scale or the DSM-IV for MD.
人类血清素基因（SLC6A4）基于启动子的长度多态性（5-HTTLPR）与情绪性表型，如重度抑郁症（MD）和人格特质神经质（N）之间的关联并不一致。已提出多种解释来解释这种差异，包括实验设计的效能不足以及性别比例、年龄和种族的差异。
在此，我们描述了在从两个同质人群中根据N分数的极端性选择的样本（n = 88,142和20,921）中，对5-HTTLPR基因座与N和MD之间的关联进行的三项独立测试。统计效能计算表明，在5%的α水平下，这些样本保留了100%的效能来检测仅占表型变异0.5%的遗传效应。年龄效应从表型测量中进行回归分析，并将性别作为协变量纳入。
无论应用何种遗传作用模式，均未在N或MD表型上鉴定出基因型的统计学显著效应（在所有情况下，p≥0.26）。
我们的数据不支持以下假设，即5-HTTLPR变异对由艾森克人格问卷N量表或MD的《精神疾病诊断与统计手册第四版》所索引的人类情绪性有显著贡献。
