Wolfson Centre for Young People's Mental Health, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Mol Psychiatry. 2024 Feb;29(2):238-246. doi: 10.1038/s41380-023-02319-1. Epub 2023 Nov 21.
Anxiety and depression (emotional disorders) are familial and heritable, especially when onset is early. However, other cross-generational studies suggest transmission of youth emotional problems is explained by mainly environmental risks. We set out to test the contribution of parental non-transmitted genetic liability, as indexed by psychiatric/neurodevelopmental common polygenic liability, to youth emotional problems using a UK population-based cohort: the Millennium Cohort Study. European (N = 6328) and South Asian (N = 814) ancestries were included, as well as a subset with genomic data from both parents (European: N = 2809; South Asian: N = 254). We examined the association of transmitted (PGS) and non-transmitted polygenic scores (PGS) for anxiety, depression, bipolar disorder and neurodevelopmental disorders (attention-deficit/hyperactivity disorder [ADHD], autism spectrum disorder [ASD], schizophrenia) with youth emotional disorder and symptom scores, measured using the parent- and self-reported Strengths and Difficulties Questionnaire emotional subscale at 6 timepoints between ages 3-17 years. In the European sample, PGS for anxiety and depression, but not bipolar disorder, were associated with emotional disorder and symptom scores across all ages, except age 3, with strongest association in adolescence. ADHD and ASD PGS also showed association across ages 11-17 years. In the South Asian sample, evidence for associations between all PGS and outcome measures were weaker. There was weak evidence of association between PGS for anxiety and depression and age 17 symptom scores in the South Asian sample, but not in the European sample for any outcome. Overall, PGS for depression, anxiety, ADHD and ASD contributed to youth emotional problems, with stronger associations in adolescence. There was limited support for non-transmitted genetic effects: these findings do not support the hypothesis that parental polygenic psychiatric/neurodevelopmental liability confer risk to offspring emotional problems through non-transmitted rearing/nurture effects.
焦虑和抑郁（情绪障碍）具有家族遗传性，尤其是在发病较早时。然而，其他跨代研究表明，青年情绪问题的传递主要是由环境风险解释的。我们着手使用英国基于人群的队列：千禧年队列研究，来检验父母未传递的遗传易感性（由精神/神经发育常见多基因易感性指数表示）对青年情绪问题的贡献。包括欧洲（N=6328）和南亚（N=814）血统，以及来自父母双方的基因组数据子集（欧洲：N=2809；南亚：N=254）。我们研究了焦虑、抑郁、双相情感障碍和神经发育障碍（注意力缺陷/多动障碍[ADHD]、自闭症谱系障碍[ASD]、精神分裂症）的传递多基因评分（PGS）和未传递多基因评分（PGS）与青年情绪障碍和症状评分之间的关联，使用父母和自我报告的优势和困难问卷情绪子量表在 3-17 岁之间的 6 个时间点进行测量。在欧洲样本中，焦虑和抑郁的 PGS 与所有年龄段的情绪障碍和症状评分相关，除了 3 岁以外，在青春期相关性最强。ADHD 和 ASD 的 PGS 也与 11-17 岁的年龄相关。在南亚样本中，所有 PGS 与结果测量之间关联的证据较弱。南亚样本中，PGS 与焦虑和抑郁的年龄 17 岁症状评分之间存在微弱的关联，但在欧洲样本中，任何结果均不存在关联。总体而言，PGS 对抑郁、焦虑、ADHD 和 ASD 与青年情绪问题相关，在青春期相关性更强。未传递遗传效应的证据较弱：这些发现不支持父母多基因精神/神经发育易感性通过未传递的养育/培养效应对后代情绪问题赋予风险的假设。
