Stein Murray B, Schork Nicholas J, Gelernter Joel
Department of Psychiatry, University of California San Diego, San Diego, California, USA.
Biol Psychiatry. 2004 Aug 15;56(4):217-24. doi: 10.1016/j.biopsych.2004.05.020.
We examined the possibility that allelic variation leading to alterations in beta(1)-adrenergic function might be present in persons with elevated social anxiety-related traits.
A sample of 504 undergraduate college students were phenotyped on a personality inventory (the NEO-Personality Inventory-Revised) and measures of shyness and social anxiety and genotyped for two beta(1) adrenergic (ADRB1 gene) polymorphisms: a serine/glycine substitution at amino acid 49 (Ser49Gly) and an arginine/glycine substitution at residue 389 (Arg389Gly). We hypothesized that the Gly49 variant (thought to be functional), but not variation at Arg389Gly, would be associated with (low) extraversion and shyness. We evaluated the potential for population stratification artifact by genotyping a set of 36 unlinked, highly polymorphic markers previously demonstrated to sufficiently distinguish the ancestry of major American populations.
Presence of a Gly49 allele was associated with an increased odds of having low or very low extraversion (odds ratio = 1.68, 95% confidence interval 1.05-2.71). The Arg389Gly polymorphism, although in tight linkage disequilibrium (D' = -1.00) with Ser49Gly, was not significantly associated with level of extraversion. Formal testing showed that population structure did not explain the findings.
The Ser49Gly functional polymorphism in the beta(1) adrenergic receptor might explain some of the population variance in extraversion and related personality traits. Population structure was excluded as an explanation for these findings. We used a sufficient marker set to exclude possible population stratification artifact. These findings should be replicated and extended to the study of psychiatric disorders marked by low extraversion, namely social phobia and other phobic disorders.
我们研究了社交焦虑相关特质升高的人群中可能存在导致β1 - 肾上腺素能功能改变的等位基因变异的可能性。
对504名本科大学生样本进行了人格量表（修订版大五人格量表）、羞怯和社交焦虑测量的表型分析，并对两个β1 - 肾上腺素能（ADRB1基因）多态性进行基因分型：氨基酸49处的丝氨酸/甘氨酸替代（Ser49Gly）和残基389处的精氨酸/甘氨酸替代（Arg389Gly）。我们假设Gly49变异体（被认为具有功能）而非Arg389Gly处的变异与（低）外向性和羞怯有关。我们通过对一组36个不连锁的高度多态性标记进行基因分型来评估群体分层假象的可能性，这些标记先前已被证明足以区分主要美国人群的血统。
Gly49等位基因的存在与低或极低外向性的几率增加相关（优势比 = 1.68，95%置信区间1.05 - 2.71）。Arg389Gly多态性虽然与Ser49Gly处于紧密连锁不平衡（D' = -1.00），但与外向性水平无显著关联。正式检验表明群体结构不能解释这些发现。
β1 - 肾上腺素能受体中的Ser49Gly功能多态性可能解释外向性及相关人格特质在人群中的部分差异。群体结构被排除作为这些发现的解释。我们使用了足够的标记集来排除可能的群体分层假象。这些发现应在以低外向性为特征的精神疾病研究中进行重复和扩展，即社交恐惧症和其他恐惧症。
