Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Transl Psychiatry. 2012 Apr 17;2(4):e102. doi: 10.1038/tp.2012.27.
The personality traits of neuroticism and extraversion are predictive of a number of social and behavioural outcomes and psychiatric disorders. Twin and family studies have reported moderate heritability estimates for both traits. Few associations have been reported between genetic variants and neuroticism/extraversion, but hardly any have been replicated. Moreover, the ones that have been replicated explain only a small proportion of the heritability (<~2%). Using genome-wide single-nucleotide polymorphism (SNP) data from ~12,000 unrelated individuals we estimated the proportion of phenotypic variance explained by variants in linkage disequilibrium with common SNPs as 0.06 (s.e. = 0.03) for neuroticism and 0.12 (s.e. = 0.03) for extraversion. In an additional series of analyses in a family-based sample, we show that while for both traits ~45% of the phenotypic variance can be explained by pedigree data (that is, expected genetic similarity) one third of this can be explained by SNP data (that is, realized genetic similarity). A part of the so-called 'missing heritability' has now been accounted for, but some of the reported heritability is still unexplained. Possible explanations for the remaining missing heritability are that: (i) rare variants that are not captured by common SNPs on current genotype platforms make a major contribution; and/ or (ii) the estimates of narrow sense heritability from twin and family studies are biased upwards, for example, by not properly accounting for nonadditive genetic factors and/or (common) environmental factors.
神经质和外向性这两种人格特质可以预测许多社会和行为结果以及精神障碍。双胞胎和家庭研究报告称,这两种特质都具有中等程度的遗传可遗传性。遗传变异与神经质/外向性之间的关联很少有报道,但几乎没有得到重复验证。此外,那些已经得到重复验证的关联仅解释了遗传可遗传性的一小部分(<~2%)。我们利用来自约 12000 名无血缘关系个体的全基因组单核苷酸多态性(SNP)数据,估计与常见 SNP 处于连锁不平衡状态的变异解释表型方差的比例为神经质的 0.06(标准误=0.03),外向性的 0.12(标准误=0.03)。在基于家族的样本中的一系列额外分析中,我们表明,虽然这两种特质的表型方差约有 45%可以用系谱数据(即预期的遗传相似性)来解释,但其中三分之一可以用 SNP 数据(即实际的遗传相似性)来解释。现在已经解释了一部分所谓的“缺失遗传力”,但仍有一部分遗传力无法解释。对于剩余的缺失遗传力,可能的解释是:(i)当前基因型平台上常见 SNP 无法捕获的罕见变异可能起主要作用;和/或(ii)来自双胞胎和家庭研究的狭义遗传度估计值偏高,例如,由于没有正确考虑非加性遗传因素和/或(常见)环境因素。