DeWan Andrew T, Cahill Megan E, Cornejo-Sanchez Diana M, Li Yining, Dong Zihan, Fabiha Tabassum, Sun Hao, Wang Gao, Leal Suzanne M
Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, United States.
Center for Statistical Genetics, Gertrude H. Sergievsky Centerand the Department of Neurology, Columbia University Medical Center, New York, NY, United States.
Front Genet. 2023 Jun 12;14:1129389. doi: 10.3389/fgene.2023.1129389. eCollection 2023.
Asthma, type 2 diabetes (T2D), and anthropometric measures are correlated complex traits that all have a major genetic component. To investigate the overlap in genetic variants associated with these complex traits. Using United Kingdom Biobank data, we performed univariate association analysis, fine-mapping, and mediation analysis to identify and dissect shared genomic regions associated with asthma, T2D, height, weight, body mass index (BMI), and waist circumference (WC). We found several genome-wide significant variants in and around the gene that are associated with asthma, T2D, or height with two of these variants shared by the three phenotypes. We also observed an association in this region with WC when adjusted for BMI. However, there was no association with WC when it was not adjusted for BMI or weight. Additionally, only suggestive associations between variants in this region and BMI were observed. Fine-mapping analyses suggested that within there are non-overlapping regions harboring causal susceptibility variants for asthma, T2D, and height. Mediation analyses supported the conclusion that these are independent associations. Our findings indicate that variants in the are associated with asthma, T2D, and height, but the associated causal variant(s) are different for each of the three phenotypes.
哮喘、2型糖尿病（T2D）和人体测量指标是具有相关性的复杂性状，它们都有一个主要的遗传成分。为了研究与这些复杂性状相关的基因变异的重叠情况，我们利用英国生物银行的数据进行了单变量关联分析、精细定位和中介分析，以识别和剖析与哮喘、T2D、身高、体重、体重指数（BMI）和腰围（WC）相关的共享基因组区域。我们在该基因及其周围发现了几个全基因组显著变异，这些变异与哮喘、T2D或身高相关，其中有两个变异为三种表型所共有。当对BMI进行校正时，我们还观察到该区域与WC存在关联。然而，在未对BMI或体重进行校正时，与WC无关联。此外，仅观察到该区域变异与BMI之间存在提示性关联。精细定位分析表明，在该区域内存在非重叠区域，这些区域包含哮喘、T2D和身高的因果易感性变异。中介分析支持了这些是独立关联的结论。我们的研究结果表明，该区域的变异与哮喘、T2D和身高相关，但三种表型各自相关的因果变异不同。
