Social, Genetic and Developmental Psychiatry Cent re, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Division of Psychology and Language Sciences, University College London, London, UK.
Transl Psychiatry. 2018 Oct 17;8(1):223. doi: 10.1038/s41398-018-0269-5.
Twin studies have shown that emotional problems (anxiety and depression) in childhood and adolescence are moderately heritable (~20-50%). In contrast, DNA-based 'SNP heritability' estimates are generally <15% and non-significant. One notable feature of emotional problems is that they can be somewhat transient, but the moderate stability seen across time and across raters is predominantly influenced by stable genetic influences. This suggests that by capturing what is in common across time and across raters, we might be more likely to tap into any underlying genetic vulnerability. We therefore hypothesised that a phenotype capturing the pervasive stability of emotional problems would show higher heritability. We fitted single-factor latent trait models using 12 emotional problems measures across ages 7, 12 and 16, rated by parents, teachers and children themselves in the Twins Early Development Study sample. Twin and SNP heritability estimates for stable emotional problems (N = 6110 pairs and 6110 unrelated individuals, respectively) were compared to those for individual measures. Twin heritability increased from 45% on average for individual measures to 76% (se = 0.023) by focusing on stable trait variance. SNP heritability rose from 5% on average (n.s.) to 14% (se = 0.049; p = 0.002). Heritability was also higher for stable within-rater composites. Polygenic scores for both adult anxiety and depression significantly explained variance in stable emotional problems (0.4%; p = 0.0001). The variance explained was more than in most individual measures. Stable emotional problems also showed significant genetic correlation with adult depression and anxiety (average = 52%). These results demonstrate the value of examining stable emotional problems in gene-finding and prediction studies.
双生子研究表明，儿童和青少年时期的情绪问题（焦虑和抑郁）具有中等程度的遗传性（~20-50%）。相比之下，基于 DNA 的“SNP 遗传力”估计通常<15%且无统计学意义。情绪问题的一个显著特征是它们可能有些短暂，但在时间和评估者之间观察到的适度稳定性主要受到稳定遗传影响的影响。这表明，通过捕捉跨时间和跨评估者的共同点，我们可能更有可能利用任何潜在的遗传脆弱性。因此，我们假设，一个捕捉情绪问题普遍稳定性的表型将显示出更高的遗传性。我们使用 12 种情绪问题测量方法，在 Twins Early Development Study 样本中，由父母、教师和儿童自身在 7、12 和 16 岁时进行评估，对单一因素潜在特质模型进行拟合。对稳定情绪问题（分别有 6110 对双胞胎和 6110 个无关个体的 N = 6110 对）的双生子和 SNP 遗传力估计与个体测量值进行了比较。通过关注稳定的特质方差，个体测量的平均双生子遗传力从 45%增加到 76%（se = 0.023）。SNP 遗传力从平均 5%（不显著）上升到 14%（se = 0.049；p = 0.002）。稳定的同评者综合评分也具有更高的遗传性。成人焦虑和抑郁的多基因评分显著解释了稳定情绪问题的方差（0.4%；p = 0.0001）。解释的方差大于大多数个体测量值。稳定的情绪问题与成人抑郁和焦虑的遗传相关性也显著（平均 = 52%）。这些结果表明，在基因发现和预测研究中检查稳定的情绪问题具有价值。
