Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder.
Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder.
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DOI：
10.1038/s41398-020-01121-9
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发表时间：
2021-02-02
影响因子：
6.8
通讯作者：
Arnold PD
中科院分区：
文献类型：
--
作者：
Burton CL;Lemire M;Xiao B;Corfield EC;Erdman L;Bralten J;Poelmans G;Yu D;Shaheen SM;Goodale T;Sinopoli VM;OCD Working Group of the Psychiatric Genomics Consortium;Soreni N;Hanna GL;Fitzgerald KD;Rosenberg D;Nestadt G;Paterson AD;Strug LJ;Schachar RJ;Crosbie J;Arnold PD
使用一种新的基于特征的测量方法，我们检查了与强迫症（OC）特征相关的遗传变异，并测试了OC特征和强迫症（OCD）是否具有遗传风险。我们使用多伦多强迫症量表（TOCS）对来自社区的5018名无关白人儿童和青少年（Spit for Science样本）进行了OC性状的全基因组关联分析（GWAS）。我们使用对所有现有强迫症病例的荟萃分析，检验了社区中与OC性状相关的遗传变异与临床强迫症相关的假设。共同的遗传风险之间的OC性状和强迫症在各自的样本中使用多基因风险评分和遗传相关分析。PTPRD（蛋白酪氨酸磷酸酶δ）内含子中的rs7856850标记的位点在全基因组显著性水平上与OC性状显著相关（p = 2.48 × 10−8）。rs7856850在OCD病例/对照全基因组数据集的荟萃分析中也与OCD相关（p = 0.0069）。影响的方向与社区样本相同。在病例/对照数据集中，OC特征的多基因风险评分与OCD显著相关，反之亦然（p < 0.01）。OC性状与强迫症有高度但不显著的遗传相关性（rg = 0.71，p = 0.062）。我们报告了PTPRD中OC性状的第一个经验证的全基因组显著变异，该变异位于先前OCD GWAS中最显著位点的下游。在社区样本中测量的OC性状与OCD病例/对照状态共享遗传风险。我们的研究结果证明了在社区样本中使用基于特征的方法进行遗传发现的可行性和力量。
Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level (p = 2.48 × 10−8). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets (p = 0.0069). The direction of effect was the same as in the community sample. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa (p’s < 0.01). OC traits were highly, but not significantly, genetically correlated with OCD (rg = 0.71, p = 0.062). We report the first validated genome-wide significant variant for OC traits in PTPRD, downstream of the most significant locus in a previous OCD GWAS. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the feasibility and power of using trait-based approaches in community samples for genetic discovery.
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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：
6.7
作者：
Gray, Simon M.;Bloch, Michael H.
通讯作者：
Bloch, Michael H.
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.
影响因子：
6.8
作者：
Burton CL;Park LS;Corfield EC;Forget-Dubois N;Dupuis A;Sinopoli VM;Shan J;Goodale T;Shaheen SM;Crosbie J;Schachar RJ;Arnold PD
通讯作者：
Arnold PD
影响因子：
3.6
作者：
Crosbie J;Arnold P;Paterson A;Swanson J;Dupuis A;Li X;Shan J;Goodale T;Tam C;Strug LJ;Schachar RJ
通讯作者：
Schachar RJ