Polygenic Heterogeneity Across Obsessive-Compulsive Disorder Subgroups Defined by a Comorbid Diagnosis.
Polygenic Heterogeneity Across Obsessive-Compulsive Disorder Subgroups Defined by a Comorbid Diagnosis.
复制标题
DOI：
10.3389/fgene.2021.711624
复制
发表时间：
2021
影响因子：
3.7
通讯作者：
Mattheisen M
中科院分区：
文献类型：
--
作者：
Strom NI;Grove J;Meier SM;Bækvad-Hansen M;Becker Nissen J;Damm Als T;Halvorsen M;Nordentoft M;Mortensen PB;Hougaard DM;Werge T;Mors O;Børglum AD;Crowley JJ;Bybjerg-Grauholm J;Mattheisen M
在强迫症（OCD）患者中，65-85%的患者在其一生中同时或在其他时间点表现出另一种精神障碍。强迫症是高度遗传的，就像它的许多合并症一样。然而，强迫症与其合并症相关的可能的遗传异质性尚未得到详尽的探讨。我们使用不同方法的框架来研究强迫症与三种常见合并症的遗传关系，即重度抑郁症（MDD）、注意力缺陷多动障碍（ADHD）和自闭症谱系障碍（ASD）。首先，利用大规模全基因组关联研究中公开的汇总统计数据，我们比较了OCD、MDD、ADHD和ASD与861种躯体和精神健康表型的遗传相关模式。其次，我们使用来自伦德贝克综合精神病学研究基金会（iPSYCH）的独立未发表数据，研究了与强迫症、MDD、ADHD和ASD显示异质性相关模式的8个特征的多基因风险评分（PRS）如何在强迫症共病亚组中划分。共病亚组包括仅患有强迫症（N = 366）、强迫症与重度抑郁症（N = 1052）、强迫症与多动症（N = 443）、强迫症与ASD （N = 388）、强迫症合并1种以上共病（N = 429）的患者。我们发现，除BMI外，所有特征的PRS在所有亚组中均与强迫症显著相关（神经质：p = 1.19 × 10 - 32，双相情感障碍：p = 7.51 × 10 - 8，神经性厌食症：p = 3.52 × 10 - 20，初产年龄：p = 9.38 × 10 - 5，受教育程度：p = 1.56 × 10 - 4，强迫症：p = 1.87 × 10 - 6，失眠：p = 2.61 × 10 - 5, BMI: p = 0.15）。对于初产年龄、受教育程度和失眠，共病亚组的PRS估计差异显著（p = 2.29 × 10−4,p = 1.63 × 10−4,p = 0.045）。特别是对于神经性厌食症、初生年龄、受教育程度、失眠和神经质，从强迫症、重度抑郁症、多动症和ASD的遗传相关性分析中得出的相关模式反映在与各自的强迫症共病组的PRS关联中。通过剖析多基因结构，我们发现强迫症共病亚组的多基因在数量和质量上都存在异质性。
Among patients with obsessive-compulsive disorder (OCD), 65–85% manifest another psychiatric disorder concomitantly or at some other time point during their life. OCD is highly heritable, as are many of its comorbidities. A possible genetic heterogeneity of OCD in relation to its comorbid conditions, however, has not yet been exhaustively explored. We used a framework of different approaches to study the genetic relationship of OCD with three commonly observed comorbidities, namely major depressive disorder (MDD), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). First, using publicly available summary statistics from large-scale genome-wide association studies, we compared genetic correlation patterns for OCD, MDD, ADHD, and ASD with 861 somatic and mental health phenotypes. Secondly, we examined how polygenic risk scores (PRS) of eight traits that showed heterogeneous correlation patterns with OCD, MDD, ADHD, and ASD partitioned across comorbid subgroups in OCD using independent unpublished data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The comorbid subgroups comprised of patients with only OCD (N = 366), OCD and MDD (N = 1,052), OCD and ADHD (N = 443), OCD and ASD (N = 388), and OCD with more than 1 comorbidity (N = 429). We found that PRS of all traits but BMI were significantly associated with OCD across all subgroups (neuroticism: p = 1.19 × 10−32, bipolar disorder: p = 7.51 × 10−8, anorexia nervosa: p = 3.52 × 10−20, age at first birth: p = 9.38 × 10−5, educational attainment: p = 1.56 × 10−4, OCD: p = 1.87 × 10−6, insomnia: p = 2.61 × 10−5, BMI: p = 0.15). For age at first birth, educational attainment, and insomnia PRS estimates significantly differed across comorbid subgroups (p = 2.29 × 10−4, p = 1.63 × 10−4, and p = 0.045, respectively). Especially for anorexia nervosa, age at first birth, educational attainment, insomnia, and neuroticism the correlation patterns that emerged from genetic correlation analysis of OCD, MDD, ADHD, and ASD were mirrored in the PRS associations with the respective comorbid OCD groups. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across OCD comorbid subgroups.
登录
查看更多内容
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)
DOI：
10.1093/bioinformatics/btz633
发表时间：
2020-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Lam M;Awasthi S;Watson HJ;Goldstein J;Panagiotaropoulou G;Trubetskoy V;Karlsson R;Frei O;Fan CC;De Witte W;Mota NR;Mullins N;Brügger K;Lee SH;Wray NR;Skarabis N;Huang H;Neale B;Daly MJ;Mattheisen M;Walters R;Ripke S
通讯作者：
Ripke S
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：
10.1002/ajmg.b.32687
发表时间：
2019-09-01
影响因子：
2.8
作者：
Khramtsova, Ekaterina A.;Heldman, Raphael;Zai, Gwyneth
通讯作者：
Zai, Gwyneth
影响因子：
1.9
作者：
Bozorgmehr, Ali;Ghadirivasfi, Mohammad;Ananloo, Esmaeil Shahsavand
通讯作者：
Ananloo, Esmaeil Shahsavand