Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder.
Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder.
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DOI：
10.1001/jamapsychiatry.2017.3485
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发表时间：
2018-01-01
期刊：
影响因子：
25.8
通讯作者：
Escott-Price V
中科院分区：
文献类型：
--
作者：
Allardyce J;Leonenko G;Hamshere M;Pardiñas AF;Forty L;Knott S;Gordon-Smith K;Porteous DJ;Haywood C;Di Florio A;Jones L;McIntosh AM;Owen MJ;Holmans P;Walters JTR;Craddock N;Jones I;O'Donovan MC;Escott-Price V
本病例对照研究旨在探讨精神分裂症的多基因易感性与双相情感障碍的精神病性表现之间的关系。精神分裂症相关的多基因易感性与双相情感障碍中精神病性症状的情绪不一致的发生和水平之间的关系是什么？在这项病例对照研究中，包括4436例双相情感障碍，4976例精神分裂症，和9012名对照，有一个多基因风险的确定-反应梯度。精神分裂症的相关性最强，其次是双相情感障碍与显著的情绪不一致的精神病特征，双相情感障碍与情绪一致的精神病特征，双相情感障碍与无精神病;所有差异相关性均具有统计学显著性。这项研究显示了精神分裂症和双相情感障碍的遗传易感性梯度，由精神病的发生和情绪不一致的水平来索引。双相情感障碍（BD）在临床表现和遗传倾向方面与精神分裂症重叠。为了了解潜在的疾病过程和机制，需要在当前诊断类别之外对患者进行分层的替代方法。探讨精神分裂症常见变异易感性（以多基因风险评分（PRS）为指标）与BD精神病性表现之间的关系。这项在英国进行的病例对照研究使用多项逻辑回归来估计不同类别的病例和对照之间的PRS相关性。最终分析的参与者是来自双相情感障碍研究网络的4436例BD病例。这些病例与来自1型糖尿病遗传学联盟研究和苏格兰一代研究的4976例精神分裂症和9012例对照的基因型数据进行了比较。数据收集于2000年1月1日至2013年12月31日之间。数据分析于2016年3月1日至2017年2月28日进行。在第二次精神病基因组学联盟精神分裂症全基因组关联研究中，使用关联阈值为P < .05的等位基因计算标准化PRS，并针对前10个群体主成分和基因分型平台进行调整。多项logit模型估计PRS与BD的关联，根据BD的研究诊断标准亚型、精神病的终生发生率和终生情绪不一致的精神病特征分层。有序逻辑回归研究不同程度的情绪不一致的PRS协会。评分来自神经精神病学访谈中的临床评估计划和双相情感障碍量表。在4436例BD病例中，2966例（67%）为女性患者，访视时的平均（SD）年龄为46 [12]岁。在所有临床表型中，有一个确定-反应梯度，与精神分裂症的PRS关联最强（风险比[RR] = 1.94; 95% CI，1.86-2.01），其次为情感性BD（RR = 1.37; 95%CI，1.22-1.54）、双相I型障碍亚型（RR = 1.30; 95%CI，1.24-1.36）和双相II型障碍亚型（RR = 1.04; 95%CI，0.97-1.11）。在BD病例中，有一个效应梯度，以精神病的性质为指标。显著的情绪不一致性精神病特征具有最强的相关性（RR = 1.46; 95%CI，1.36-1.57），其次是情绪一致性精神病（RR = 1.24; 95%CI，1.17-1.33）和无精神病史的BD（RR = 1.09; 95%CI，1.04-1.15）。迄今为止，一项研究首次显示了精神分裂症和BD的多基因风险梯度，以情绪不一致的精神病症状的发生和水平为索引。
This case-control study examines the association between polygenic liability for schizophrenia and psychotic presentations of bipolar disorder. What is the association between schizophrenia-related polygenic liability and the occurrence and level of mood-incongruence of psychotic symptoms in bipolar disorder? In this case-control study involving 4436 cases of bipolar disorder, 4976 cases of schizophrenia, and 9012 controls, there was an exposure-response gradient of polygenic risk. Schizophrenia had the strongest association, followed by bipolar disorder with prominent mood-incongruent psychotic features, bipolar disorder with mood-congruent psychotic features, and bipolar disorder with no psychosis; all differential associations were statistically significant. This study shows a gradient of genetic liability across schizophrenia and bipolar disorder, indexed by the occurrence of psychosis and level of mood incongruence. Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes and mechanisms. To investigate the association between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRSs), and psychotic presentations of BD. This case-control study in the United Kingdom used multinomial logistic regression to estimate differential PRS associations across categories of cases and controls. Participants included in the final analyses were 4436 cases of BD from the Bipolar Disorder Research Network. These cases were compared with the genotypic data for 4976 cases of schizophrenia and 9012 controls from the Type 1 Diabetes Genetics Consortium study and the Generation Scotland study. Data were collected between January 1, 2000, and December 31, 2013. Data analysis was conducted from March 1, 2016, to February 28, 2017. Standardized PRSs, calculated using alleles with an association threshold of P < .05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, were adjusted for the first 10 population principal components and genotyping platforms. Multinomial logit models estimated PRS associations with BD stratified by Research Diagnostic Criteria subtypes of BD, by lifetime occurrence of psychosis, and by lifetime mood-incongruent psychotic features. Ordinal logistic regression examined PRS associations across levels of mood incongruence. Ratings were derived from the Schedules for Clinical Assessment in Neuropsychiatry interview and the Bipolar Affective Disorder Dimension Scale. Of the 4436 cases of BD, 2966 (67%) were female patients, and the mean (SD) age at interview was 46 [12] years. Across clinical phenotypes, there was an exposure-response gradient, with the strongest PRS association for schizophrenia (risk ratio [RR] = 1.94; 95% CI, 1.86-2.01), followed by schizoaffective BD (RR = 1.37; 95% CI, 1.22-1.54), bipolar I disorder subtype (RR = 1.30; 95% CI, 1.24-1.36), and bipolar II disorder subtype (RR = 1.04; 95% CI, 0.97-1.11). Within BD cases, there was an effect gradient, indexed by the nature of psychosis. Prominent mood-incongruent psychotic features had the strongest association (RR = 1.46; 95% CI, 1.36-1.57), followed by mood-congruent psychosis (RR = 1.24; 95% CI, 1.17-1.33) and BD with no history of psychosis (RR = 1.09; 95% CI, 1.04-1.15). For the first time to date, a study shows a polygenic-risk gradient across schizophrenia and BD, indexed by the occurrence and level of mood-incongruent psychotic symptoms.
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DOI：
10.1177/1740774510373497
发表时间：
2010
期刊：
Clinical trials (London, England)
影响因子：
--
作者：
Hilner JE;Perdue LH;Sides EG;Pierce JJ;Wägner AM;Aldrich A;Loth A;Albret L;Wagenknecht LE;Nierras C;Akolkar B;T1DGC
通讯作者：
T1DGC
影响因子：
2.1
作者：
Dudbridge F
通讯作者：
Dudbridge F
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
6.6
作者：
Derks, Eske M.;Allardyce, Judith;Ophoff, Roel A.
通讯作者：
Ophoff, Roel A.
影响因子：
4.4
作者：
Amador, Carmen;Huffman, Jennifer;Haley, Chris S.
通讯作者：
Haley, Chris S.