학술논문
Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes
Document Type
article
Author
Lu, Yingchang; Dimitrov, Latchezar; Chen, Shyh-Huei; Bielak, Lawrence F; Bis, Joshua C; Feitosa, Mary F; Lu, Lingyi; Kavousi, Maryam; Raffield, Laura M; Smith, Albert V; Wang, Lihua; Weiss, Stefan; Yao, Jie; Zhu, Jiaxi; Gudmundsson, Elias F; Gudmundsdottir, Valborg; Bos, Daniel; Ghanbari, Mohsen; Ikram, M Arfan; Hwang, Shih-Jen; Taylor, Kent D; Budoff, Matthew J; Gíslason, Gauti K; O’Donnell, Christopher J; An, Ping; Franceschini, Nora; Freedman, Barry I; Fu, Yi-Ping; Guo, Xiuqing; Heiss, Gerardo; Kardia, Sharon LR; Wilson, James G; Langefeld, Carl D; Schminke, Ulf; Uitterlinden, André G; Lange, Leslie A; Peyser, Patricia A; Gudnason, Vilmundur G; Psaty, Bruce M; Rotter, Jerome I; Bowden, Donald W; Ng, Maggie CY
Source
Circulation Genomic and Precision Medicine. 14(4)
Subject
Language
Abstract
BackgroundCoronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.MethodsWe performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.ResultsWe replicated 2 loci (rs9369640 and rs9349379 near PHACTR1 and rs10757278 near CDKN2B) for CAC and one locus for cIMT (rs7412 and rs445925 near APOE-APOC1) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near CSNK1A1L/LINC00547/POSTN at 13q13.3) at P=2.0×10-8 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints POSTN, encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (P