Center for Statistical Science, Tsinghua University, Beijing, China.
Department of Industrial Engineering, Tsinghua University, Beijing, China.
Nat Commun. 2021 Apr 1;12(1):2033. doi: 10.1038/s41467-021-22334-6.
Genetic correlation analysis has quickly gained popularity in the past few years and provided insights into the genetic etiology of numerous complex diseases. However, existing approaches oversimplify the shared genetic architecture between different phenotypes and cannot effectively identify precise genetic regions contributing to the genetic correlation. In this work, we introduce LOGODetect, a powerful and efficient statistical method to identify small genome segments harboring local genetic correlation signals. LOGODetect automatically identifies genetic regions showing consistent associations with multiple phenotypes through a scan statistic approach. It uses summary association statistics from genome-wide association studies (GWAS) as input and is robust to sample overlap between studies. Applied to seven phenotypically distinct but genetically correlated neuropsychiatric traits, we identify 227 non-overlapping genome regions associated with multiple traits, including multiple hub regions showing concordant effects on five or more traits. Our method addresses critical limitations in existing analytic strategies and may have wide applications in post-GWAS analysis.
遗传相关分析在过去几年中迅速流行起来,为许多复杂疾病的遗传病因提供了新的见解。然而,现有的方法过于简化了不同表型之间的共享遗传结构,并且不能有效地识别导致遗传相关性的精确遗传区域。在这项工作中,我们引入了 LOGODetect,这是一种强大而高效的统计方法,用于识别包含局部遗传相关信号的小基因组片段。LOGODetect 通过扫描统计方法自动识别与多个表型一致关联的遗传区域。它使用来自全基因组关联研究 (GWAS) 的汇总关联统计数据作为输入,并且对研究之间的样本重叠具有鲁棒性。将其应用于七个表型明显不同但遗传上相关的神经精神特征,我们确定了 227 个与多个特征相关的非重叠基因组区域,包括多个枢纽区域,这些区域对五个或更多特征表现出一致的影响。我们的方法解决了现有分析策略中的关键局限性,并且可能在 GWAS 后分析中有广泛的应用。