虽然多基因风险评分(PRS)预测精神病问题,这些关联可能归因于间接途径,包括人口分层,配种交配,或王朝效应(通过父母环境调解)。这项研究的目的是检查PRS-精神症状关联是否归因于间接途径和直接途径。
样品由3,907个双合子(DZ)双胞胎对组成。在童年,他们的父母对他们的症状进行了98次评估。在青春期(n=2,393DZ对),父母和双胞胎都认为自己有20种症状。我们从童年数据中提取了一个一般因素和七个具体因素,青少年数据中的一个一般因素和三个具体因素。然后,我们将每个一般因素模型同时回归到十个精神病学PRS上。我们首先在个体(β)之间进行回归,然后在DZ双胞胎对(βw)内进行回归,控制间接途径。
在童年,ADHD的PRS预测一般精神病理学(β=0.09,95%CI:[0.06,0.12];βw=0.07[0.01,0.12])。此外,ADHD的PRS可预测特定的注意力不集中(β=0.04[0.00,0.08];βw=0.09[0.01,0.17])和特定的多动(β=0.07[0.04,0.11];βw=0.09[0.01,0.16]);精神分裂症的PRS可预测特定的学习(β=0.08[0.03,0.13];βw=0.0.02[0.01,β9];β=0.01,总的来说,PRS-一般因子关联在个体之间和双胞胎对中相似,而PRS特异性因子相关性成对扩增了84%。
这意味着PRS-精神症状关联似乎并不归因于间接途径,如人口分层,配种交配,或通过父母环境进行调解。相反,遗传学似乎直接影响症状学。
Although polygenic risk scores (PRS) predict psychiatric problems, these associations might be attributable to indirect pathways including population stratification, assortative mating, or dynastic effects (mediation via parental environments). The goal of this study was to examine whether PRS-psychiatric symptom associations were attributable to indirect versus direct pathways.
The sample consisted of 3,907 dizygotic (DZ) twin pairs. In childhood, their parents rated them on 98 symptoms. In adolescence (n = 2,393 DZ pairs), both the parents and the twins rated themselves on 20 symptoms. We extracted one general and seven specific factors from the childhood data, and one general and three specific factors from the adolescent data. We then regressed each general factor model onto ten psychiatric PRS simultaneously. We first conducted the regressions between individuals (β) and then within DZ twin pairs (βw ), which controls for indirect pathways.
In childhood, the PRS for ADHD predicted general psychopathology (β = 0.09, 95% CI: [0.06, 0.12]; βw = 0.07 [0.01, 0.12]). Furthermore, the PRS for ADHD predicted specific inattention (β = 0.04 [0.00, 0.08]; βw = 0.09 [0.01, 0.17]) and specific hyperactivity (β = 0.07 [0.04, 0.11]; βw = 0.09 [0.01, 0.16]); the PRS for schizophrenia predicted specific learning (β = 0.08 [0.03, 0.13]; βw = 0.19 [0.08, 0.30]) and specific inattention problems (β = 0.05 [0.01, 0.09]; βw = 0.10 [0.02, 0.19]); and the PRS for neuroticism predicted specific anxiety (β = 0.06 [0.02, 0.10]; βw = 0.06 [0.00, 0.12]). Overall, the PRS-general factor associations were similar between individuals and within twin pairs, whereas the PRS-specific factors associations amplified by 84% within pairs.
This implies that PRS-psychiatric symptom associations did not appear attributable to indirect pathways such as population stratification, assortative mating, or mediation via parental environments. Rather, genetics appeared to directly influence symptomatology.