scholarly journals Identification of Susceptibility Loci for Cardiovascular Disease in Adults With Hypertension, Diabetes and Dyslipidemia 

2020 ◽  
Author(s):  
Youhyun Song ◽  
Ja-Eun Choi ◽  
Yu-Jin Kwon ◽  
Hyuk-Jae Chang ◽  
Jung Oh Kim ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Cardiovascular Disease ◽  
Metabolic Diseases ◽  
Phase 1 ◽  
Case Control ◽  
Control Group ◽  
Susceptibility Loci ◽  
Positional Candidate ◽  
Genome Wide ◽  
A Genome

Abstract Background: Hypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are well-known risk factors of cardiovascular disease (CVD), but not all patients develop CVDs. Studies have been limited investigating genetic risk of CVDs specific to individuals with metabolic diseases. This study aimed to identify disease-specific and/or common genetic loci associated with CVD susceptibility in chronic metabolic disease patients.Methods: We conducted a genome-wide association study (GWAS) of a multiple case-control design with data from the City Cohort within Health EXAminees subcohort of the Korean Genome and Epidemiology Study (KoGES_HEXA). KoGES_HEXA is a population-based prospective cohort of 173,357 urban Korean adults that had health examinations at medical centers. 42,393 participants (16,309 HTN; 5,314 DM; 20,770 DL) were analyzed, and each metabolic disease group was divided into three CVD case-controls: coronary artery disease (CAD), ischemic stroke (IS), and cardio-cerebrovascular disease (CCD). GWASs were conducted for each case-control group with 7,975,321 imputed single nucleotide polymorphisms using Phase 1/2 Asian panels from 1000 Genomes Project, by logistic regression and controlled for confounding variables. Genome-wide significant levels were implemented to identify important susceptibility loci.Results: Totaling 42,393 individuals, this study included 16,309 HTN (mean age [SD], 57.28 [7.45]; 816 CAD, 398 IS, and 1,185 CCD cases), 5,314 DM (57.79 [7.39]; 361 CAD, 153 IS, and 497 CCD cases), and 20,770 DL patients (55.34 [7.63]; 768 CAD, 295 IS, and 1,039 CCD cases). Six genome-wide significant CVD risk loci were identified, with relatively large effect sizes: 1 locus in HTN (HTN-CAD: 17q25.3/CBX8-CBX4 [OR, 2.607; P = 6.37 × 10−9]), 2 in DM (DM-IS: 4q32.3/MARCH1-LINC01207 [OR, 5.587; P = 1.34 × 10−8], and DM-CCD: 17q25.3/RPTOR [OR, 3.511; P = 1.99 × 10−8]), and 3 in DL (DL-CAD: 9q22.2/UNQ6494-LOC101927847 [OR, 2.282; P = 7.78 × 10−9], DL-IS: 3p22.1/ULK4 [OR, 2.162; P = 2.97 × 10−8], and DL-CCD: 2p22.2/CYP1B1-CYP1B1-AS1 [OR, 2.027; P = 4.24 × 10−8]).Conclusions: This study identified 6 susceptibility loci and positional candidate genes for CVDs in HTN, DM, and DL patients using an unprecedented study design. 1 locus (17q25.3) was commonly associated with CAD. These associations warrant validation in additional studies for potential therapeutic applications.

scholarly journals Identification of susceptibility loci for cardiovascular disease in adults with hypertension, diabetes, and dyslipidemia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Youhyun Song ◽  
Ja-Eun Choi ◽  
Yu-Jin Kwon ◽  
Hyuk-Jae Chang ◽  
Jung Oh Kim ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Cardiovascular Disease ◽  
Genome Wide Association Study ◽  
Metabolic Diseases ◽  
Case Control ◽  
Control Group ◽  
Susceptibility Loci ◽  
Positional Candidate ◽  
Genome Wide ◽  
A Genome

Abstract Background Hypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are well-known risk factors of cardiovascular disease (CVD), but not all patients develop CVDs. Studies have been limited investigating genetic risk of CVDs specific to individuals with metabolic diseases. This study aimed to identify disease-specific and/or common genetic loci associated with CVD susceptibility in chronic metabolic disease patients. Methods We conducted a genome-wide association study (GWAS) of a multiple case–control design with data from the City Cohort within Health EXAminees subcohort of the Korean Genome and Epidemiology Study (KoGES_HEXA). KoGES_HEXA is a population-based prospective cohort of 173,357 urban Korean adults that had health examinations at medical centers. 42,393 participants (16,309 HTN; 5,314 DM; 20,770 DL) were analyzed, and each metabolic disease group was divided into three CVD case-controls: coronary artery disease (CAD), ischemic stroke (IS), and cardio-cerebrovascular disease (CCD). GWASs were conducted for each case–control group with 7,975,321 imputed single nucleotide polymorphisms using the Phase 3 Asian panel from 1000 Genomes Project, by logistic regression and controlled for confounding variables. Genome-wide significant levels were implemented to identify important susceptibility loci. Results Totaling 42,393 individuals, this study included 16,309 HTN (mean age [SD], 57.28 [7.45]; 816 CAD, 398 IS, and 1,185 CCD cases), 5,314 DM (57.79 [7.39]; 361 CAD, 153 IS, and 497 CCD cases), and 20,770 DL patients (55.34 [7.63]; 768 CAD, 295 IS, and 1,039 CCD cases). Six genome-wide significant CVD risk loci were identified, with relatively large effect sizes: 1 locus in HTN (HTN-CAD: 17q25.3/CBX8-CBX4 [OR, 2.607; P = 6.37 × 10−9]), 2 in DM (DM-IS: 4q32.3/MARCH1-LINC01207 [OR, 5.587; P = 1.34 × 10−8], and DM-CCD: 17q25.3/RPTOR [OR, 3.511; P = 1.99 × 10−8]), and 3 in DL (DL-CAD: 9q22.2/UNQ6494-LOC101927847 [OR, 2.282; P = 7.78 × 10−9], DL-IS: 3p22.1/ULK4 [OR, 2.162; P = 2.97 × 10−8], and DL-CCD: 2p22.2/CYP1B1-CYP1B1-AS1 [OR, 2.027; P = 4.24 × 10−8]). Conclusions This study identified 6 susceptibility loci and positional candidate genes for CVDs in HTN, DM, and DL patients using an unprecedented study design. 1 locus (17q25.3) was commonly associated with CAD. These associations warrant validation in additional studies for potential therapeutic applications.

scholarly journals A Genome-Wide Association Study in Early COPD: Identification of One Major Susceptibility Loci

2020 ◽  
Vol Volume 15 ◽  
pp. 2967-2975
Author(s):  
Ye-Jin Lee ◽  
SeungHo Choi ◽  
Sung-Youn Kwon ◽  
Yunhwan Lee ◽  
Jung Kyu Lee ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome

scholarly journals A Nonsense Variant in Hephaestin Like 1 (HEPHL1) Is Responsible for Congenital Hypotrichosis in Belted Galloway Cattle

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 643
Author(s):  
Thibaud Kuca ◽  
Brandy M. Marron ◽  
Joana G. P. Jacinto ◽  
Julia M. Paris ◽  
Christian Gerspach ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Homozygosity Mapping ◽  
Mendelian Inheritance ◽  
Large Animal Model ◽  
Large Animal ◽  
Loss Of Function ◽  
Protein Coding ◽  
Positional Candidate ◽  
Genome Wide ◽  
A Genome

Genodermatosis such as hair disorders mostly follow a monogenic mode of inheritance. Congenital hypotrichosis (HY) belong to this group of disorders and is characterized by abnormally reduced hair since birth. The purpose of this study was to characterize the clinical phenotype of a breed-specific non-syndromic form of HY in Belted Galloway cattle and to identify the causative genetic variant for this recessive disorder. An affected calf born in Switzerland presented with multiple small to large areas of alopecia on the limbs and on the dorsal part of the head, neck, and back. A genome-wide association study using Swiss and US Belted Galloway cattle encompassing 12 cases and 61 controls revealed an association signal on chromosome 29. Homozygosity mapping in a subset of cases refined the HY locus to a 1.5 Mb critical interval and subsequent Sanger sequencing of protein-coding exons of positional candidate genes revealed a stop gain variant in the HEPHL1 gene that encodes a multi-copper ferroxidase protein so-called hephaestin like 1 (c.1684A>T; p.Lys562*). A perfect concordance between the homozygous presence of this most likely pathogenic loss-of-function variant and the HY phenotype was found. Genotyping of more than 700 purebred Swiss and US Belted Galloway cattle showed the global spread of the mutation. This study provides a molecular test that will permit the avoidance of risk matings by systematic genotyping of relevant breeding animals. This rare recessive HEPHL1-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002230-9913).

scholarly journals A Genome-Wide Search For Susceptibility Loci to Human Essential Hypertension

Hypertension ◽  
2000 ◽  
Vol 35 (6) ◽  
pp. 1291-1296 ◽  
Author(s):  
Pankaj Sharma ◽  
Jennie Fatibene ◽  
Franco Ferraro ◽  
Haiyan Jia ◽  
Sue Monteith ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Search

A genome-wide scan for schizophrenia and psychosis susceptibility loci in families of Mexican and Central American ancestry

2007 ◽  
Vol 144B (2) ◽  
pp. 193-199 ◽  
Author(s):  
M.A. Escamilla ◽  
A. Ontiveros ◽  
H. Nicolini ◽  
H. Raventos ◽  
R. Mendoza ◽  
...  
Keyword(s):  
Central American ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Scan

scholarly journals Genome-wide association of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) plasma levels in the ELSA-Brasil study

2020 ◽  
Author(s):  
Isabela Bensenor ◽  
Kallyandra Padilha ◽  
Isabella Ramos Lima ◽  
Raul Dias Santos ◽  
Gilles Lambert ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Genetic Variation ◽  
Disease Incidence ◽  
Plasma Concentrations ◽  
Genome Wide Association ◽  
Interindividual Variation ◽  
Lipid Lowering ◽  
Proprotein Convertase ◽  
Genome Wide ◽  
A Genome

AbstractPharmacological inhibition of PCSK9 (proprotein convertase subtilisin/kexin type 9) is an established therapeutic option to treat hypercholesterolemia and plasma PCSK9 levels have been implicated in cardiovascular disease incidence. A number of genetic variants within the PCSK9 gene locus have been shown to modulate PCSK9 levels, but these only explain a very small percentage of the overall PCSK9 interindividual variation. Here we present data on the genetic association structure between PCSK9 levels and genome-wide genetic variation in a healthy sample from the general population.We performed a genome-wide association study of plasma PCSK9 levels in a sample of Brazilian individuals enrolled in the ELSA-Brasil cohort (n=810). Enrolled individuals were free from cardiovascular disease, diabetes and were not under lipid-lowering medication. Genome-wide genotyping was conducted using the Axiom_PMRA.r3 array and imputation used the TOPMED multi-ancestry sample panel. Total PCSK9 plasma concentrations were determined using the Quantikine SPC900 ELISA kit.We observed two genome-wide significant loci and seven loci that reached the pre-defined p value threshold of 1 × 10−6. Significant variants were near KCNA5 and KCNA1, and LINC00353. Genetic variation at the PCSK9 locus was able to explain approximately 4% of the overall interindividual variation in PCSK9 levels. Colocalization analysis using eQTL data suggested RWDD3, ATXN7L1, KCNA1, and FAM177A1 to be potential mediators of some of the observed associations.Our results suggest that PCSK9 levels may be modulated by trans genetic variation outside of the PCSK9 gene and this may have clinical implications. Understanding both environmental and genetic predictors of PCSK9 levels may help identifying new targets for cardiovascular disease treatment and contribute to a better assessment of the benefits of long-term PCSK9 inhibition.

scholarly journals Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis

2013 ◽  
Vol 144 (4) ◽  
pp. 799-807.e24 ◽  
Author(s):  
Ulrike Peters ◽  
Shuo Jiao ◽  
Fredrick R. Schumacher ◽  
Carolyn M. Hutter ◽  
Aaron K. Aragaki ◽  
...  
Keyword(s):  
Genetic Susceptibility ◽  
Meta Analysis ◽  
Susceptibility Loci ◽  
Colorectal Tumors ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-Wide DNA Methylation Profiles of Phlegm-Dampness Constitution

2018 ◽  
Vol 45 (5) ◽  
pp. 1999-2008 ◽  
Author(s):  
Haiqiang Yao ◽  
Shanlan Mo ◽  
Ji Wang ◽  
Yingshuai Li ◽  
Chong-Zhi Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Metabolic Disorders ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Body Type ◽  
Peripheral Blood Mononuclear ◽  
Molecular Features ◽  
Genome Wide ◽  
A Genome ◽  
Differentially Methylated Genes

Background/Aims: Metabolic diseases are leading health concerns in today’s global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. Methods: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs). Eight volunteers had PC and 4 had balanced constitutions. Results: Methylation data indicated a genome-scale hyper-methylation pattern in PC. We located 288 differentially methylated probes (DMPs). A total of 256 genes were mapped, and some of these were metabolic-related. SQSTM1, DLGAP2 and DAB1 indicated diabetes mellitus; HOXC4 and SMPD3, obesity; and GRWD1 and ATP10A, insulin resistance. According to Ingenuity Pathway Analysis (IPA), differentially methylated genes were abundant in multiple metabolic pathways. Conclusion: Our results suggest the potential risk for metabolic disorders in individuals with PC. We also explain the clinical characteristics of PC with DNA methylation features.

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