Relationship between polygenic risk scores and symptom dimensions of schizophrenia and schizotypy in multiplex families with schizophrenia.
Relationship between polygenic risk scores and symptom dimensions of schizophrenia and schizotypy in multiplex families with schizophrenia.
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DOI：
10.1192/bjp.2022.179
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发表时间：
2023-07
期刊：
影响因子：
--
通讯作者：
Riley BP
中科院分区：
文献类型：
--
作者：
Ahangari M;Bustamante D;Kirkpatrick R;Nguyen TH;Verrelli BC;Fanous A;Kendler KS;Webb BT;Bacanu SA;Riley BP
精神分裂症先证者亲属中精神障碍和典型特征的聚集。目前尚不清楚精神分裂症先证者及其亲属的症状维度的变异性如何与精神疾病的多基因易感性相关。探讨多基因风险评分（PRS）是否可以预测精神分裂症多重家系成员的症状维度。精神分裂症、双相情感障碍和重度抑郁症的最大全基因组数据集被用于构建来自爱尔兰高密度多重精神分裂症家族研究的861名参与者的PRS。症状维度是使用精神障碍的操作标准检查表在有精神病发作史的参与者中得出的，而在没有精神病发作史的参与者中使用精神分裂症的结构化访谈得出的。混合效应线性回归模型被用来评估整个精神病谱的PRS和症状维度之间的关系。在有精神病发作史的参与者中，精神分裂症PRS与阴性/紊乱症状维度显著相关（P = 2.31 × 10−4），在无精神病发作史的参与者中，与阴性维度显著相关（P = 1.42 × 10−3）。在有精神病发作史的受试者中，双相情感障碍PRS与躁狂症状维度显著相关（P = 3.70 × 10−4）。没有观察到与重性抑郁症PRS的关联。精神分裂症的多基因易感性与有精神病发作史的参与者中较高的阴性/紊乱症状和无精神病发作史的参与者中阴性症状相关。这些结果提供了支持精神分裂症谱模型的遗传学证据，并支持这样一种观点，即阴性和紊乱症状可能比阳性症状具有更大的遗传基础，使其成为精神分裂症家族易感性的更好指标。
Psychotic disorders and schizotypal traits aggregate in the relatives of probands with schizophrenia. It is currently unclear how variability in symptom dimensions in schizophrenia probands and their relatives is associated with polygenic liability to psychiatric disorders. To investigate whether polygenic risk scores (PRSs) can predict symptom dimensions in members of multiplex families with schizophrenia. The largest genome-wide data-sets for schizophrenia, bipolar disorder and major depressive disorder were used to construct PRSs in 861 participants from the Irish Study of High-Density Multiplex Schizophrenia Families. Symptom dimensions were derived using the Operational Criteria Checklist for Psychotic Disorders in participants with a history of a psychotic episode, and the Structured Interview for Schizotypy in participants without a history of a psychotic episode. Mixed-effects linear regression models were used to assess the relationship between PRS and symptom dimensions across the psychosis spectrum. Schizophrenia PRS is significantly associated with the negative/disorganised symptom dimension in participants with a history of a psychotic episode (P = 2.31 × 10−4) and negative dimension in participants without a history of a psychotic episode (P = 1.42 × 10−3). Bipolar disorder PRS is significantly associated with the manic symptom dimension in participants with a history of a psychotic episode (P = 3.70 × 10−4). No association with major depressive disorder PRS was observed. Polygenic liability to schizophrenia is associated with higher negative/disorganised symptoms in participants with a history of a psychotic episode and negative symptoms in participants without a history of a psychotic episode in multiplex families with schizophrenia. These results provide genetic evidence in support of the spectrum model of schizophrenia, and support the view that negative and disorganised symptoms may have greater genetic basis than positive symptoms, making them better indices of familial liability to schizophrenia.
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DOI：
10.1038/s41537-022-00317-w
发表时间：
2022-11-25
期刊：
SCHIZOPHRENIA
影响因子：
--
作者：
Ahangari, Mohammad;Kirkpatrick, Robert;Nguyen, Tan-Hoang;Gillespie, Nathan;Kendler, Kenneth S.;Bacanu, Silviu-Alin;Webb, Bradley T.;Verrelli, Brian C.;Riley, Brien P.
通讯作者：
Riley, Brien P.
影响因子：
0.8
作者：
Galarza CE;Lachos VH;Bandyopadhyay D
通讯作者：
Bandyopadhyay D
影响因子：
30.8
作者：
Loh, Po-Ru;Danecek, Petr;Palamara, Pier Francesco;Fuchsberger, Christian;Reshef, Yakir A.;Finucane, Hilary K.;Schoenherr, Sebastian;Forer, Lukas;McCarthy, Shane;Abecasis, Goncalo R.;Durbin, Richard;Price, Alkes L.
通讯作者：
Price, Alkes L.
影响因子：
10.5
作者：
Cardno, AG;Sham, PC;McGuffin, P
通讯作者：
McGuffin, P
影响因子：
6.9
作者：
Nenadic，Igor;Meller，Tina;Kircher，Tilo
通讯作者：
Kircher，Tilo