Multi-tissue transcriptome-wide association study identifies novel candidate genes and pleiotropy effects across four abdominal hernia subtypes.

IF 3.3 Q2 GENETICS & HEREDITY
Dima L Chaar, Chen Jiang, Brandon Cowan, Sahil Patel, Mark Kvale, Jie Yin, Rouzbeh Mostaedi, Nadav Ahituv, Eric Jorgenson, Thomas J Hoffmann, Hélène Choquet
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引用次数: 0

Abstract

Abdominal hernias are caused by the protrusion of an organ or tissue through a weakened abdominal wall. Genome-wide association studies (GWASs) have identified 81 genetic susceptibility loci for different hernia subtypes, with 26 loci associated with more than one hernia type; however, additional work is needed to prioritize causal genes at known GWAS loci, identify novel ones, and characterize shared genetic effects across hernia subtypes. We conduct transcriptome-wide association study (TWAS) analyses of four hernia subtypes (i.e., inguinal, umbilical, ventral, femoral) using GWAS summary statistics from up to 57,291 hernia cases and 436,717 controls of European ancestry. Our TWAS, which leveraged imputed gene expression from 54 tissues, identifies 211 unique genes, of which 85 did not overlap with known hernia-associated loci. We also investigate patterns of pleiotropy and identify four genes (LYPLAL1-AS1, RIMKLBP2, AL513283.1, and EFEMP1) associated with all four hernia subtypes. Our findings enhance understanding of transcriptomic mechanisms through which hernias develop.

多组织转录组关联研究确定了四种腹疝亚型的新候选基因和多效性效应。
腹疝是由一个器官或组织通过脆弱的腹壁突出引起的。全基因组关联研究(GWASs)已经确定了81个不同疝亚型的遗传易感位点,其中26个位点与一种以上的疝类型相关;然而,需要进一步的工作来确定已知GWAS基因座上的致病基因的优先级,识别新的基因,并表征疝气亚型之间共有的遗传效应。我们对四种疝气亚型(即腹股沟、脐、腹、股)进行了转录组全关联研究(TWAS)分析,使用了57,291例疝气病例和436,717例欧洲血统对照的GWAS汇总统计数据。我们的TWAS利用了来自54个组织的输入基因表达,鉴定出211个独特的基因,其中85个与已知的疝气相关位点不重叠。我们还研究了多效性模式,并确定了与所有四种疝气亚型相关的四个基因(LYPLAL1-AS1, RIMKLBP2, AL513283.1和EFEMP1)。我们的发现增强了对疝气发生的转录组学机制的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
HGG Advances
HGG Advances Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
4.30
自引率
4.50%
发文量
69
审稿时长
14 weeks
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