Genomic Correlation, Shared Loci, and Causal Relationship Between Bullous Pemphigoid and Atopic Dermatitis: A Large-Scale Genome-Wide Cross-Trait Analysis.
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引用次数: 0
Abstract
Background: Bullous pemphigoid (BP) and atopic dermatitis (AD) are currently thought to be tightly related, yet studies of the mechanisms of co-morbidities are lacking.
Methods: We obtained GWAS data for BP (N = 376,274) and AD (N = 796,661) from the Finnish Genetic Research Program dataset and the UK Biobank, separately. Then, the following four analyses were performed: (1) cross-trait linkage disequilibrium score regression (LDSC) to assess the genetic correlation between BP and AD, (2) cross-phenotype association analysis (CPASSOC) to identify multiple effector loci shared by BP and AD, (3) transcriptome-wide association study (TWAS) to determine whether their cross-organizational expression patterns share genes with a common biological mechanism of relevance, and (4) bidirectional Mendelian randomization (MR) analysis to assess bidirectional causal effects of BP and AD.
Results: We found a positive genetic association between BP and AD (rg = 0.5476, p = 0.0495) as well as identified four pleiotropic loci and 59 common genes affecting BP and AD. Bidirectional MR analysis suggested that BP promotes the risk of AD.
Conclusions: We revealed a genetic link between BP and AD, which is associated with biological pleiotropy and causality. Awareness of the association between BP and AD helps dermatologists manage patients with these illnesses.
背景：目前认为大疱性类天疱疮（BP）和特应性皮炎（AD）密切相关，但缺乏对并发症机制的研究：我们分别从芬兰遗传研究计划数据集和英国生物库中获得了BP（376 274人）和AD（796 661人）的GWAS数据。然后，进行了以下四项分析：(1）跨性状连锁不平衡得分回归（LDSC），以评估 BP 和 AD 之间的遗传相关性；（2）交叉表型关联分析（CPASSOC），以确定 BP 和 AD 共享的多个效应位点；（3）转录组范围关联研究（TWAS），以确定它们的跨组织表达模式是否共享具有共同生物学机制的相关基因；（4）双向孟德尔随机化（MR）分析，以评估 BP 和 AD 的双向因果效应。结果我们发现血压和注意力缺失症之间存在正向遗传关联（rg = 0.5476，p = 0.0495），并确定了影响血压和注意力缺失症的 4 个多效基因位点和 59 个共同基因。双向MR分析表明，血压会增加AD的发病风险：我们揭示了血压与注意力缺失症之间的遗传联系，这种联系与生物多效性和因果关系有关。对血压和注意力缺失症之间关联的认识有助于皮肤科医生管理这些疾病的患者。
期刊介绍：
Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care.
Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.
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