Open AccessIdentification of novel functional CpG-SNPs associated with type 2 diabetes and coronary artery disease
Author(s) -
Zun Wang,
Chuan Qiu,
Xu Lin,
LanJuan Zhao,
Yong Liu,
Xinrui Wu,
Qian Wang,
Wei Liu,
Kelvin Li,
HongWen Deng,
Siyuan Tang,
Hui Shen
Publication year - 2020
Publication title -
molecular genetics and genomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.921
H-Index - 120
eISSN - 1617-4615
pISSN - 1617-4623
DOI - 10.1007/s00438-020-01651-3
Subject(s) - single nucleotide polymorphism , biology , expression quantitative trait loci , quantitative trait locus , genome wide association study , genetics , genetic association , cpg site , type 2 diabetes , coronary artery disease , dna methylation , gene , diabetes mellitus , medicine , genotype , endocrinology , gene expression
Genome-wide association studies (GWASs) have identified hundreds of single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D) and coronary artery disease (CAD), respectively. Nevertheless, these studies were generally performed for single-trait/disease and failed to assess the pleiotropic role of the identified variants. To identify novel functional loci and the pleiotropic relationship between CAD and T2D, the targeted cFDR analysis on CpG-SNPs was performed by integrating two independent large and multi-centered GWASs with summary statistics of T2D (26,676 cases and 132,532 controls) and CAD (60,801 cases and 123,504 controls). Applying the cFDR significance threshold of 0.05, we observed a pleiotropic enrichment between T2D and CAD by incorporating pleiotropic effects into a conditional analysis framework. We identified 79 novel CpG-SNPs for T2D, 61 novel CpG-SNPs for CAD, and 18 novel pleiotropic loci for both traits. Among these novel CpG-SNPs, 33 of them were annotated as methylation quantitative trait locus (meQTL) in whole blood, and ten of them showed expression QTL (eQTL), meQTL, and metabolic QTL (metaQTL) effects simultaneously. To the best of our knowledge, we performed the first targeted cFDR analysis on CpG-SNPs, and our findings provided novel insights into the shared biological mechanisms and overlapped genetic heritability between T2D and CAD.