Dissecting clinical heterogeneity of bipolar disorder using multiple polygenic risk scores.
Dissecting clinical heterogeneity of bipolar disorder using multiple polygenic risk scores.
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DOI：
10.1038/s41398-020-00996-y
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发表时间：
2020-09-18
影响因子：
6.8
通讯作者：
Biernacka JM
中科院分区：
文献类型：
--
作者：
Coombes BJ;Markota M;Mann JJ;Colby C;Stahl E;Talati A;Pathak J;Weissman MM;McElroy SL;Frye MA;Biernacka JM
双相情感障碍(BD)具有高度的临床异质性、频繁的精神共病和较高的自杀风险。为了确定BD常见临床亚型之间的遗传差异，我们使用来自一系列精神、个性和生活方式特征的多个PR进行了系统的多基因风险评分(PR)分析，以剖析两个BD队列中BD亚型的差异：梅奥诊所BD生物库(N = 968)和遗传协会信息网(N = 1001)。通过问卷调查和DSM-IV的结构化临床访谈，参与者被评估了精神病史、早发性BD、快速自行车(定义为一年中四次或四次以上的发作)和自杀企图。在1969年双相情感障碍的合并样本中(45.5%的男性)，精神病患者SCZ的RR较高(OR = 1.3per S.D.；p = 3e-5)，而快感缺失(OR = 0.87；p = 0.003)和体重指数(OR = 0.87；p = 0.003)的RR较低。快速循环组ADHD(OR = 1.23；p = 7e-5)和MDD(OR = 1.23；p = 4e-5)的RR较高，BD PR(OR = 0.8；p = 0.004)较低。自杀未遂者在精神疾病(OR = 1.26；p = 1e-6)和快感障碍(OR = 1.22；p = 2e-5)方面的比率较高，而在教育程度(OR = 0.87；p = 0.003)方面的比率较低。观察到的新的PR与亚表型的相关性与临床观察一致，例如快速循环的BD患者一生中ADHD的患病率更高。我们的发现证实了遗传异质性导致了BD的临床异质性，考虑到基因对精神障碍的精神病理成分的贡献可能会改善复杂精神疾病的遗传预测。
Bipolar disorder (BD) has high clinical heterogeneity, frequent psychiatric comorbidities, and elevated suicide risk. To determine genetic differences between common clinical sub-phenotypes of BD, we performed a systematic polygenic risk score (PRS) analysis using multiple PRSs from a range of psychiatric, personality, and lifestyle traits to dissect differences in BD sub-phenotypes in two BD cohorts: the Mayo Clinic BD Biobank (N = 968) and Genetic Association Information Network (N = 1001). Participants were assessed for history of psychosis, early-onset BD, rapid cycling (defined as four or more episodes in a year), and suicide attempts using questionnaires and the Structured Clinical Interview for DSM-IV. In a combined sample of 1969 bipolar cases (45.5% male), those with psychosis had higher PRS for SCZ (OR = 1.3 per S.D.; p = 3e-5) but lower PRSs for anhedonia (OR = 0.87; p = 0.003) and BMI (OR = 0.87; p = 0.003). Rapid cycling cases had higher PRS for ADHD (OR = 1.23; p = 7e-5) and MDD (OR = 1.23; p = 4e-5) and lower BD PRS (OR = 0.8; p = 0.004). Cases with a suicide attempt had higher PRS for MDD (OR = 1.26; p = 1e-6) and anhedonia (OR = 1.22; p = 2e-5) as well as lower PRS for educational attainment (OR = 0.87; p = 0.003). The observed novel PRS associations with sub-phenotypes align with clinical observations such as rapid cycling BD patients having a greater lifetime prevalence of ADHD. Our findings confirm that genetic heterogeneity contributes to clinical heterogeneity of BD and consideration of genetic contribution to psychopathologic components of psychiatric disorders may improve genetic prediction of complex psychiatric disorders.
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影响因子：
11
作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
通讯作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
DOI：
10.1097/01.chi.0000135619.38392.78
发表时间：
2004-10-01
影响因子：
13.3
作者：
Brent, DA;Oquendo, M;Mann, JJ
通讯作者：
Mann, JJ
影响因子：
25.8
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
通讯作者：
Escott-Price V
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