scholarly journals Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke

2019 ◽  
Vol 8 (3) ◽  
pp. 332 ◽  
Author(s):  
Chia-Shan Hsieh ◽  
Pang-Shuo Huang ◽  
Sheng-Nan Chang ◽  
Cho-Kai Wu ◽  
Juey-Jen Hwang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Signaling Pathway ◽  
Copy Number ◽  
Genetic Factors ◽  
Copy Number Variations ◽  
Nucleotide Polymorphisms ◽  
Thromboembolic Stroke ◽  
Genome Wide ◽  
A Genome ◽  
The Impact

Atrial fibrillation (AF) is a common cardiac arrhythmia and is one of the major causes of ischemic stroke. In addition to the clinical factors such as CHADS2 or CHADS2-VASC score, the impact of genetic factors on the risk of thromboembolic stroke in patients with AF has been largely unknown. Single-nucleotide polymorphisms in several genomic regions have been found to be associated with AF. However, these loci do not contribute to all the genetic risks of AF or AF related thromboembolic risks, suggesting that there are other genetic factors or variants not yet discovered. In the human genome, copy number variations (CNVs) could also contribute to disease susceptibility. In the present study, we sought to identify CNVs determining the AF-related thromboembolic risk. Using a genome-wide approach in 109 patients with AF and thromboembolic stroke and 14,666 controls from the Taiwanese general population (Taiwan Biobank), we first identified deletions in chromosomal regions 1p36.32-1p36.33, 5p15.33, 8q24.3 and 19p13.3 and amplifications in 14q11.2 that were significantly associated with AF-related stroke in the Taiwanese population. In these regions, 148 genes were involved, including several microRNAs and long non-recoding RNAs. Using a pathway analysis, we found deletions in GNB1, PRKCZ, and GNG7 genes related to the alpha-adrenergic receptor signaling pathway that play a major role in determining the risk of an AF-related stroke. In conclusion, CNVs may be genetic predictors of a risk of a thromboembolic stroke for patients with AF, possibly pointing to an impaired alpha-adrenergic signaling pathway in the mechanism of AF-related thromboembolism.

A genome-wide association study of copy number variations with umbilical hernia in swine

2016 ◽  
Vol 47 (3) ◽  
pp. 298-305 ◽  
Author(s):  
Yi Long ◽  
Ying Su ◽  
Huashui Ai ◽  
Zhiyan Zhang ◽  
Bin Yang ◽  
...  
Keyword(s):  
Association Study ◽  
Copy Number ◽  
Umbilical Hernia ◽  
Genome Wide Association Study ◽  
Copy Number Variations ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Re-analysis of a Genome-Wide Gene-By-Environment Interaction Study of Case Parent Trios, Adjusted for Population Stratification

2021 ◽  
Vol 11 ◽  
Author(s):  
Pulindu Ratnasekera ◽  
Brad McNeney
Keyword(s):  
East Asian ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Multivitamin Supplementation ◽  
Gene Environment ◽  
Genome Wide ◽  
A Genome ◽  
The Impact ◽  
East Asian Ancestry

We investigate the impact of confounding on the results of a genome-wide association analysis by Beaty et al., which identified multiple single nucleotide polymorphisms that appeared to modify the effect of maternal smoking, alcohol consumption, or multivitamin supplementation on risk of cleft palate. The study sample of case-parent trios was primarily of European and East Asian ancestry, and the distribution of all three exposures differed by ancestral group. Such differences raise the possibility that confounders, rather than the exposures, are the risk modifiers and hence that the inference of gene-environment (G×E) interaction may be spurious. Our analyses generally confirmed the result of Beaty et al. and suggest the interaction G×E is driven by the European trios, whereas the East Asian trios were less informative.

scholarly journals Comparative analyses of copy number variations between Bos taurus and Bos indicus

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yan Hu ◽  
Han Xia ◽  
Mingxun Li ◽  
Chang Xu ◽  
Xiaowei Ye ◽  
...  
Keyword(s):  
Copy Number ◽  
Muscle Development ◽  
Reference Genome ◽  
Bos Taurus ◽  
Bos Indicus ◽  
Copy Number Variations ◽  
Genome Wide ◽  
A Genome ◽  
Detection Strategies ◽  
Specific Sequences

Abstract Background Bos taurus and Bos indicus are two main sub-species of cattle. However, the differential copy number variations (CNVs) between them are not yet well studied. Results Based on the new high-quality cattle reference genome ARS-UCD1.2, we identified 13,234 non-redundant CNV regions (CNVRs) from 73 animals of 10 cattle breeds (4 Bos taurus and 6 Bos indicus), by integrating three detection strategies. While 6990 CNVRs (52.82%) were shared by Bos taurus and Bos indicus, large CNV differences were discovered between them and these differences could be used to successfully separate animals into two subspecies. We found that 2212 and 538 genes uniquely overlapped with either indicine-specific CNVRs and or taurine-specific CNVRs, respectively. Based on FST, we detected 16 candidate lineage-differential CNV segments (top 0.1%) under selection, which overlapped with eight genes (CTNNA1, ENSBTAG00000004415, PKN2, BMPER, PDE1C, DNAJC18, MUSK, and PLCXD3). Moreover, we obtained 1.74 Mbp indicine-specific sequences, which could only be mapped on the Bos indicus reference genome UOA_Brahman_1. We found these sequences and their associated genes were related to heat resistance, lipid and ATP metabolic process, and muscle development under selection. We further analyzed and validated the top significant lineage-differential CNV. This CNV overlapped genes related to muscle cell differentiation, which might be generated from a retropseudogene of CTH but was deleted along Bos indicus lineage. Conclusions This study presents a genome wide CNV comparison between Bos taurus and Bos indicus. It supplied essential genome diversity information for understanding of adaptation and phenotype differences between the Bos taurus and Bos indicus populations.

The Impact of Constitutional Copy Number Variants in Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 496-496
Author(s):  
Matthew W Jenner ◽  
David C Johnson ◽  
Paola E Leone ◽  
Brian A Walker ◽  
David Gonzalez ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Change ◽  
Copy Number Variations ◽  
Genomic Variation ◽  
Chromosome 21 ◽  
Nucleotide Polymorphisms ◽  
Copy Number Changes ◽  
The Impact ◽  
First Time ◽  
Tumor Dna

Abstract Single nucleotide polymorphisms (SNPs) have been long regarded as being important in determining variation and disease predisposition. Recently, chromosomal structural variation in the form of deletions, insertions and duplifications have been identified frequently in the genome of the general population. Such copy number variations (CNVs) have been shown to contribute to a range of human diseases. In recent studies we have utilized Affymetrix 50K and 500K arrays to identify acquired copy number change in myeloma tumor samples. In those studies we had access to paired constitutional DNA and in the present study have been able to report for the first time a CNV map of the constitutional genome of myeloma patients. Affymetrix 500K mapping arrays were used to identify copy number changes in 63 paired samples using DNA from peripheral blood and CD138 selected plasma cells. Tumor samples were analyzed in CNAG using both a paired and unpaired analysis to distinguish between inherited and acquired copy number change. Constitutional DNA was analyzed by both CNAG and GEMCA using 90 Caucasian samples from the Hapmap database as a reference set. For maximum calling accuracy, only those regions identified by both algorithms were called as CNVs. As with similar studies, overlapping CNVs identified using this approach were merged to generate a list of CNV regions (CNVRs) characteristic of the constitutional DNA of these myeloma cases. Using this approach, we identified 292 CNVs across 63 cases, with a median of 4 regions per sample. There were 155 discrete CNVRs, of which 46 were recurrent. The recurrent CNVRs were found most frequently in the pericentric regions of chromosome 14 and 15 in keeping with other studies. We then compared these recurrent CNVRs with a comparable dataset of normal individuals generated using Affymetrix 500K arrays. In this analysis, 25/46 recurrent CNVRs in the myeloma cases were novel. The two most frequent novel CNVRs in the myeloma cases were gains on chromosome 21 and 15. We also compared the characteristics of the constitutional CNVs with the acquired copy number changes in the corresponding tumor samples and identified that the constitutional CNVs were generally considerably smaller. However, using unpaired analysis it was possible to determine the presence of the constitutional CNV in the tumor sample, providing validation of the CNVs. We were also able to demonstrate that acquired copy number change in the tumor cells can either exaggerate or ameliorate the effect of the inherited CNV in the tumor genome, such as cases with acquired trisomy 15 and deletion or gain of regions of 15q in the constitutional DNA. These findings also reinforce the need for paired non-tumor DNA when undertaking copy number analysis of tumor DNA using SNP arrays. In this study we have been able to identify for the first time the presence of CNVs in the constitutional genome of individuals with myeloma. We have been able to systematically catalogue these CNVRs. These results provide the basis for future studies aimed at identifying how this type of genomic variation may influence the development of and outcome of myeloma and a broad range of other hematological conditions.

scholarly journals Genome-wide copy number variations in a large cohort of bantu African children

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Feyza Yilmaz ◽  
Megan Null ◽  
David Astling ◽  
Hung-Chun Yu ◽  
Joanne Cole ◽  
...  
Keyword(s):  
Copy Number ◽  
Developmental Disorders ◽  
African Ancestry ◽  
22Q11.2 Deletion Syndrome ◽  
Copy Number Variations ◽  
Genomic Variation ◽  
Deletion Syndrome ◽  
Genome Wide ◽  
A Genome ◽  
Genomic Regions

Abstract Background Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies including people of African descent. Methods We carried out a genome-wide copy number analysis in > 3400 healthy Bantu Africans from Tanzania. Signal intensity data from high density (> 2.5 million probes) genotyping arrays were used for CNV calling with three algorithms including PennCNV, DNAcopy and VanillaICE. Stringent quality metrics and filtering criteria were applied to obtain high confidence CNVs. Results We identified over 400,000 CNVs larger than 1 kilobase (kb), for an average of 120 CNVs (SE = 2.57) per individual. We detected 866 large CNVs (≥ 300 kb), some of which overlapped genomic regions previously associated with multiple congenital anomaly syndromes, including Prader-Willi/Angelman syndrome (Type1) and 22q11.2 deletion syndrome. Furthermore, several of the common CNVs seen in our cohort (≥ 5%) overlap genes previously associated with developmental disorders. Conclusions These findings may help refine the phenotypic outcomes and penetrance of variations affecting genes and genomic regions previously implicated in diseases. Our study provides one of the largest datasets of CNVs from individuals of African ancestry, enabling improved clinical evaluation and disease association of CNVs observed in research and clinical studies in African populations.

scholarly journals Identification of Copy Number Variation Among Nonsyndromic Cleft Lip and or Without Cleft Palate With Hypodontia: A Genome-Wide Association Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Norliana Ghazali ◽  
Normastura Abd Rahman ◽  
Azlina Ahmad ◽  
Sarina Sulong ◽  
Thirumulu Ponnuraj Kannan
Keyword(s):  
Copy Number Variation ◽  
Cleft Palate ◽  
Copy Number ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Quantitative Polymerase Chain Reaction ◽  
Copy Number Variations ◽  
Genome Wide ◽  
A Genome ◽  
Number Variation

Nonsyndromic cleft lip and or without cleft palate (NSCL/P) with the hypodontia is a common developmental abnormality in humans and animals. This study identified the genetic aberration involved in both NSCL/P and hypodontia pathogenesis. A cross-sectional study using genome-wide study copy number variation-targeted CytoScan 750K array carried out on salivary samples from 61 NSCL/P and 20 noncleft with and without hypodontia Malay subjects aged 7–13 years old. Copy number variations (CNVs) of SKI and fragile histidine triad (FHIT) were identified in NSCL/P and noncleft children using quantitative polymerase chain reaction (qPCR) as a validation analysis. Copy number calculated (CNC) for each gene determined with Applied Biosystems CopyCaller Software v2.0. The six significant CNVs included gains (12q14.3, 15q26.3, 1p36.32, and 1p36.33) and losses (3p14.2 and 4q13.2) in NSCL/P with hypodontia patients compared with the NSCL/P only. The genes located in these regions encoded LEMD3, IGF1R, TP73, SKI, FHIT, and UGT2β15. There were a significant gain and loss of both SKI and FHIT copy number in NSCL/P with hypodontia compared with the noncleft group (p < 0.05). The results supported that CNVs significantly furnish to the development of NSCL/P with hypodontia.

scholarly journals A Genome-Wide Association Study of Novel Genetic Variants Associated With Anthropometric Traits in Koreans

2021 ◽  
Vol 12 ◽  
Author(s):  
Hye-Won Cho ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Genetic Variants ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Fat Distribution ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome

Most previous genome-wide association studies (GWAS) have identified genetic variants associated with anthropometric traits. However, most of the evidence were reported in European populations. Anthropometric traits such as height and body fat distribution are significantly affected by gender and genetic factors. Here we performed GWAS involving 64,193 Koreans to identify the genetic factors associated with anthropometric phenotypes including height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip ratio. We found nine novel single-nucleotide polymorphisms (SNPs) and 59 independent genetic signals in genomic regions that were reported previously. Of the 19 SNPs reported previously, eight genetic variants at RP11-513I15.6 and one genetic variant at the RP11-977G19.10 region and six Asian-specific genetic variants were newly found. We compared our findings with those of previous studies in other populations. Five overlapping genetic regions (PAN2, ANKRD52, RNF41, HGMA1, and C6orf106) had been reported previously but none of the SNPs were independently identified in the current study. Seven of the nine newly found novel loci associated with height in women revealed a statistically significant skeletal expression of quantitative trait loci. Our study provides additional insight into the genetic effects of anthropometric phenotypes in East Asians.

Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5298-5303 ◽  
Author(s):  
David-Alexandre Trégouët ◽  
Simon Heath ◽  
Noémie Saut ◽  
Christine Biron-Andreani ◽  
Jean-François Schved ◽  
...  
Keyword(s):  
Complex Disease ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk ◽  
Fv Leiden ◽  
Gwas Approach

Abstract Venous thromboembolism (VTE) is a complex disease that has a major genetic component of risk. To identify genetic factors that may modify the risk of VTE, we conducted a genome-wide association study by analyzing approximately 317 000 single nucleotide polymorphisms (SNPs) in 453 VTE cases and 1327 controls. Only 3 SNPs located in the FV and ABO blood group genes were found associated with VTE at a genome-wide significant level of 1.7 × 10−7. Detailed analysis of these SNPs in additional cohorts of more than 1700 cases and 1400 controls revealed that the association observed at the FV locus was the result of the increased risk mediated by the FV Leiden mutation, whereas O and A2 blood groups were found to be at lower risk for VTE. Apart from the FV and ABO loci, no other locus was found strongly associated with VTE. However, using this large cohort of subjects, we were able to replicate the mild effects of 2 nonsynonymous SNPs, rs1613662 in GP6 and rs13146272 in CYP4V2, recently suspected to be associated with VTE.

scholarly journals A genome-wide survey of copy number variations in Han Chinese residing in Taiwan

Genomics ◽  
2009 ◽  
Vol 94 (4) ◽  
pp. 241-246 ◽  
Author(s):  
Chien-Hsing Lin ◽  
Ying-Chao Lin ◽  
Jer-Yuarn Wu ◽  
Wen-Harn Pan ◽  
Yuan-Tsong Chen ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variations ◽  
Han Chinese ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Survey
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