心理病理症状的多基因分数和网络。

IF 22.5 1区 医学 Q1 PSYCHIATRY JAMA Psychiatry Pub Date : 2024-09-01 DOI:10.1001/jamapsychiatry.2024.1403
Giulia G Piazza, Andrea G Allegrini, Thalia C Eley, Sacha Epskamp, Eiko Fried, Adela-Maria Isvoranu, Jonathan P Roiser, Jean-Baptiste Pingault
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引用次数: 0

摘要

重要性:有关精神特质多基因风险的研究通常采用疾病层面的表型方法,隐含地将疾病视为同质结构;然而,症状异质性无处不在,许多可能的症状组合都属于同一疾病范畴。关注单个症状可能会揭示多基因风险在精神病理学中的作用:目的:确定多基因评分是与精神障碍的所有症状相关,还是与部分指标相关,以及多基因评分是否通过特定的相关症状与合并表型相关:这项横断面研究使用了两项人群队列研究的数据。雅芳父母与子女纵向研究(ALSPAC)中的儿童数据被纳入主要分析,双胞胎早期发育研究(TEDS)中的儿童数据被纳入确认分析。数据分析时间为 2021 年 10 月至 2024 年 1 月。ALSPAC招募了居住在英格兰西南部、将于1991年至1992年分娩的孕妇。1994 年至 1996 年出生的双胞胎在 TEDS 中从人口记录中招募。主要结果和测量指标:心理病理学相关症状,如多动、亲社会性、抑郁、焦虑以及 11 岁时的同伴和行为问题。心理网络的构建包括抑郁、焦虑、注意力缺陷/多动障碍(ADHD)、体重指数(BMI)和 ALSPAC 中教育程度的个体症状和多基因评分。在进行预先登记的确认分析后,在 TEDS 中对网络模型进行了交叉验证:结果:共纳入了 5521 名 ALSPAC 参与者(平均 [SD] 年龄为 11.8 [0.14] 岁;2777 [50.3%] 为女性)和 4625 名 TEDS 参与者(平均 [SD] 年龄为 11.27 [0.69] 岁;2460 [53.2%] 为女性)。多基因得分优先与核心症状的限制性子集相关,并与其他更远的精神病理学症状间接相关(网络边缘在 r = -0.074 和 r = 0.073 之间)。精神病多基因得分与特定的跨障碍症状相关,而非精神病多基因得分与跨障碍的各种指标相关,这表明非精神病特征对合并症的潜在贡献。例如,ADHD的多基因得分与ADHD的核心症状--容易分心(r = 0.07)有关,而BMI的多基因得分与各种障碍的症状有关,包括被欺负(r = 0.053)和不思考问题(r = 0.041):在障碍层面观察到的遗传关联可能会掩盖症状层面的异质性。症状层面的研究方法可以更好地理解多基因风险在形成精神病理学和合并症方面的作用。
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Polygenic Scores and Networks of Psychopathology Symptoms.

Importance: Studies on polygenic risk for psychiatric traits commonly use a disorder-level approach to phenotyping, implicitly considering disorders as homogeneous constructs; however, symptom heterogeneity is ubiquitous, with many possible combinations of symptoms falling under the same disorder umbrella. Focusing on individual symptoms may shed light on the role of polygenic risk in psychopathology.

Objective: To determine whether polygenic scores are associated with all symptoms of psychiatric disorders or with a subset of indicators and whether polygenic scores are associated with comorbid phenotypes via specific sets of relevant symptoms.

Design, setting, and participants: Data from 2 population-based cohort studies were used in this cross-sectional study. Data from children in the Avon Longitudinal Study of Parents and Children (ALSPAC) were included in the primary analysis, and data from children in the Twins Early Development Study (TEDS) were included in confirmatory analyses. Data analysis was conducted from October 2021 to January 2024. Pregnant women based in the Southwest of England due to deliver in 1991 to 1992 were recruited in ALSPAC. Twins born in 1994 to 1996 were recruited in TEDS from population-based records. Participants with available genetic data and whose mothers completed the Short Mood and Feelings Questionnaire and the Strength and Difficulties Questionnaire when children were 11 years of age were included.

Main outcomes and measures: Psychopathology relevant symptoms, such as hyperactivity, prosociality, depression, anxiety, and peer and conduct problems at age 11 years. Psychological networks were constructed including individual symptoms and polygenic scores for depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), body mass index (BMI), and educational attainment in ALSPAC. Following a preregistered confirmatory analysis, network models were cross-validated in TEDS.

Results: Included were 5521 participants from ALSPAC (mean [SD] age, 11.8 [0.14] years; 2777 [50.3%] female) and 4625 participants from TEDS (mean [SD] age, 11.27 [0.69] years; 2460 [53.2%] female). Polygenic scores were preferentially associated with restricted subsets of core symptoms and indirectly associated with other, more distal symptoms of psychopathology (network edges ranged between r = -0.074 and r = 0.073). Psychiatric polygenic scores were associated with specific cross-disorder symptoms, and nonpsychiatric polygenic scores were associated with a variety of indicators across disorders, suggesting a potential contribution of nonpsychiatric traits to comorbidity. For example, the polygenic score for ADHD was associated with a core ADHD symptom, being easily distracted (r = 0.07), and the polygenic score for BMI was associated with symptoms across disorders, including being bullied (r = 0.053) and not thinking things out (r = 0.041).

Conclusions and relevance: Genetic associations observed at the disorder level may hide symptom-level heterogeneity. A symptom-level approach may enable a better understanding of the role of polygenic risk in shaping psychopathology and comorbidity.

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来源期刊
JAMA Psychiatry
JAMA Psychiatry PSYCHIATRY-
CiteScore
30.60
自引率
1.90%
发文量
233
期刊介绍: JAMA Psychiatry is a global, peer-reviewed journal catering to clinicians, scholars, and research scientists in psychiatry, mental health, behavioral science, and related fields. The Archives of Neurology & Psychiatry originated in 1919, splitting into two journals in 1959: Archives of Neurology and Archives of General Psychiatry. In 2013, these evolved into JAMA Neurology and JAMA Psychiatry, respectively. JAMA Psychiatry is affiliated with the JAMA Network, a group of peer-reviewed medical and specialty publications.
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