Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK.
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK.
J Affect Disord. 2019 Dec 1;259:112-120. doi: 10.1016/j.jad.2019.08.040. Epub 2019 Aug 19.
Identifying phenotypic manifestations of genetic risk for bipolar disorder (BD) in childhood could increase our understanding of aetiological mechanisms.
To examine whether BD genetic risk is associated with childhood (age 8 years) cognitive function.
Using data from the Avon Longitudinal Study of Parents and Children, we examined associations between polygenic risk scores for BD (BD-PRS) derived using Psychiatric Genomics Consortium summary data at p-thresholds (P) ≤0.01 (primary) and ≤0.5 (secondary) and several cognitive domains (sample sizes 5,613 to 5,936). We also examined whether associations were due to SNPs that have shared risk effects on schizophrenia (SZ).
At P≤0.01, the BD-PRS was associated with poorer executive functioning (ß= -0.03, 95%CI -0.06, -0.01; p = 0.013), and, more weakly with poorer processing speed (ß = -0.02, 95%CI -0.05, 0.02; p = 0.075). Evidence of association with both poorer processing speed (p = 0.016) and performance IQ (p = 0.018) was stronger at P≤0.5. Associations with performance IQ and processing speed were primarily driven by genetic effects that are shared with SZ risk, but there was some evidence of bipolar-specific genetic effects on childhood executive functioning.
The BD-PRS still explains only a small proportion of the variance for BD which will have reduced power to detect associations.
Genetic risk for BD manifests as impaired cognition in childhood, and this is driven by risk SNPs that are also shared with SZ genetic risk. Further elucidation of which cognitive domains are most affected by genetic risk for BD could help understanding of aetiology and improve prediction of BD.
识别双相情感障碍（BD）遗传风险的表型表现可以增加我们对病因机制的理解。
研究 BD 遗传风险是否与儿童（8 岁）认知功能有关。
利用英国 Avon 纵向父母和儿童研究的数据，我们使用精神疾病基因组学联盟汇总数据在 p 阈值（P）≤0.01（主要）和≤0.5（次要）下计算的 BD 多基因风险评分（BD-PRS），并检查其与几个认知领域的关联（样本量为 5613 至 5936）。我们还检查了这些关联是否归因于对精神分裂症（SZ）具有共同风险效应的 SNPs。
在 P≤0.01 时，BD-PRS 与较差的执行功能（β= -0.03，95%CI -0.06，-0.01；p=0.013）相关，与较差的加工速度的关联较弱（β= -0.02，95%CI -0.05，0.02；p=0.075）。在 P≤0.5 时，与较差的加工速度（p=0.016）和表现智商（p=0.018）的关联更强。与表现智商和加工速度的关联主要是由与 SZ 风险共享的遗传效应驱动的，但也有一些证据表明儿童执行功能的双相特异性遗传效应。
BD-PRS 仍然只能解释 BD 变异的一小部分，这会降低检测关联的能力。
BD 的遗传风险表现为儿童认知障碍，这是由与 SZ 遗传风险共享的风险 SNPs 驱动的。进一步阐明哪些认知领域受 BD 遗传风险的影响最大，可能有助于了解病因并提高 BD 的预测能力。
