Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Commun Biol. 2024 Sep 2;7(1):1077. doi: 10.1038/s42003-024-06795-1.
The aim is to investigate the evidence for shared genetic architecture between each of asthma, allergic rhinitis and eczema with gastro-esophageal reflux disease (GERD). Structural equation models (SEM) and polygenic risk score (PRS) analyses are applied to three Swedish twin cohorts (n = 46,582) and reveal a modest genetic correlation between GERD and asthma of 0.18 and bidirectional PRS and phenotypic associations ranging between OR 1.09-1.14 and no correlations for eczema and allergic rhinitis. Linkage disequilibrium score regression is applied to summary statistics of recently published GERD and asthma/allergic disease genome wide association studies and reveals a genetic correlation of 0.48 for asthma and GERD, and Genomic SEM supports a single latent factor. A gene-/gene-set analysis using MAGMA reveals six pleiotropic genes (two at 12q13.2) associated with asthma and GERD. This study provides evidence that there is a common genetic architecture unique to asthma and GERD that may explain comorbidity and requires further investigation.
目的是研究哮喘、过敏性鼻炎和特应性皮炎与胃食管反流病（GERD）之间共享遗传结构的证据。结构方程模型（SEM）和多基因风险评分（PRS）分析应用于三个瑞典双胞胎队列（n=46582），结果显示 GERD 与哮喘之间存在适度的遗传相关性，为 0.18，双向 PRS 和表型关联的范围在 OR 1.09-1.14 之间，与特应性皮炎和过敏性鼻炎无相关性。连锁不平衡评分回归应用于最近发表的 GERD 和哮喘/过敏性疾病全基因组关联研究的汇总统计数据，结果显示哮喘和 GERD 的遗传相关性为 0.48，基因组 SEM 支持单一潜在因素。使用 MAGMA 的基因/基因集分析显示，有六个与哮喘和 GERD 相关的多效基因（位于 12q13.2 上的两个）。本研究提供了证据表明，哮喘和 GERD 之间存在独特的共同遗传结构，这可能解释了共病性，需要进一步研究。
