scholarly journals Combined Analysis with Copy Number Variation Identifies Risk Loci in Lung Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Xinlei Li ◽  
Xianfeng Chen ◽  
Guohong Hu ◽  
Yang Liu ◽  
Zhenguo Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Copy Number ◽  
Association Studies ◽  
Copy Number Variations ◽  
Genome Wide Association Studies ◽  
Potential Candidate ◽  
Cancer Etiology ◽  
Combined Analysis ◽  
Recombination Hotspots ◽  
Underlying Mechanisms

Background. Lung cancer is the most important cause of cancer mortality worldwide, but the underlying mechanisms of this disease are not fully understood. Copy number variations (CNVs) are promising genetic variations to study because of their potential effects on cancer.Methodology/Principal Findings. Here we conducted a pilot study in which we systematically analyzed the association of CNVs in two lung cancer datasets: the Environment And Genetics in Lung cancer Etiology (EAGLE) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial datasets. We used a preestablished association method to test the datasets separately and conducted a combined analysis to test the association accordance between the two datasets. Finally, we identified 167 risk SNP loci and 22 CNVs associated with lung cancer and linked them with recombination hotspots. Functional annotation and biological relevance analyses implied that some of our predicted risk loci were supported by other studies and might be potential candidate loci for lung cancer studies.Conclusions/Significance. Our results further emphasized the importance of copy number variations in cancer and might be a valuable complement to current genome-wide association studies on cancer.

DNA copy number and structural variation (CNV) contributions to adult and childhood obesity

2020 ◽  
Vol 48 (4) ◽  
pp. 1819-1828
Author(s):  
Megan Phillips ◽  
Jeganathan Ramesh Babu ◽  
Xu Wang ◽  
Thangiah Geetha
Keyword(s):  
Copy Number ◽  
Current Knowledge ◽  
Association Studies ◽  
Copy Number Variations ◽  
Genomic Diversity ◽  
Health Concern ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Comprehensive Classification ◽  
Genomic Regions

In recent years, obesity has reached epidemic proportions globally and has become a major public health concern. The development of obesity is likely caused by several behavioral, environmental, and genetic factors. Genomic variability among individuals is largely due to copy number variations (CNVs). Recent genome-wide association studies (GWAS) have successfully identified many loci containing CNV related to obesity. These obesity-related CNVs are informative to the diagnosis and treatment of genomic diseases. A more comprehensive classification of CNVs may provide the basis for determining how genomic diversity impacts the mechanisms of expression for obesity in children and adults of a variety of genders and ethnicities. In this review, we summarize current knowledge on the relationship between obesity and the CNV of several genomic regions, with an emphasis on genes at the following loci: 11q11, 1p21.1, 10q11.22, 10q26.3, 16q12.2, 16p12.3, and 4q25.

scholarly journals Genome-wide detection of CNV regions and their potential association with growth and fatness traits in Duroc pigs

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yibin Qiu ◽  
Rongrong Ding ◽  
Zhanwei Zhuang ◽  
Jie Wu ◽  
Ming Yang ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Complex Traits ◽  
Copy Number ◽  
Association Studies ◽  
Average Daily Gain ◽  
Genome Wide Association Studies ◽  
Potential Candidate ◽  
Genome Wide ◽  
Number Variation ◽  
Genetic Mechanisms

Abstract Background In the process of pig breeding, the average daily gain (ADG), days to 100 kg (AGE), and backfat thickness (BFT) are directly related to growth rate and fatness. However, the genetic mechanisms involved are not well understood. Copy number variation (CNV), an important source of genetic diversity, can affect a variety of complex traits and diseases and has gradually been thrust into the limelight. In this study, we reported the genome-wide CNVs of Duroc pigs using SNP genotyping data from 6627 animals. We also performed a copy number variation region (CNVR)-based genome-wide association studies (GWAS) for growth and fatness traits in two Duroc populations. Results Our study identified 953 nonredundant CNVRs in U.S. and Canadian Duroc pigs, covering 246.89 Mb (~ 10.90%) of the pig autosomal genome. Of these, 802 CNVRs were in U.S. Duroc pigs with 499 CNVRs were in Canadian Duroc pigs, indicating 348 CNVRs were shared by the two populations. Experimentally, 77.8% of nine randomly selected CNVRs were validated through quantitative PCR (qPCR). We also identified 35 CNVRs with significant association with growth and fatness traits using CNVR-based GWAS. Ten of these CNVRs were associated with both ADG and AGE traits in U.S. Duroc pigs. Notably, four CNVRs showed significant associations with ADG, AGE, and BFT, indicating that these CNVRs may play a pleiotropic role in regulating pig growth and fat deposition. In Canadian Duroc pigs, nine CNVRs were significantly associated with both ADG and AGE traits. Further bioinformatic analysis identified a subset of potential candidate genes, including PDGFA, GPER1, PNPLA2 and BSCL2. Conclusions The present study provides a necessary supplement to the CNV map of the Duroc genome through large-scale population genotyping. In addition, the CNVR-based GWAS results provide a meaningful way to elucidate the genetic mechanisms underlying complex traits. The identified CNVRs can be used as molecular markers for genetic improvement in the molecular-guided breeding of modern commercial pigs.

scholarly journals Dissecting Molecular Genetic Mechanisms of 1q21.1 CNV in Neuropsychiatric Disorders

2021 ◽  
Vol 22 (11) ◽  
pp. 5811
Author(s):  
Joy Yoon ◽  
Yingwei Mao
Keyword(s):  
Copy Number ◽  
Association Studies ◽  
Molecular Genetic ◽  
Neuropsychiatric Disorders ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Genetic Mechanisms

Pathogenic copy number variations (CNVs) contribute to the etiology of neurodevelopmental/neuropsychiatric disorders (NDs). Increased CNV burden has been found to be critically involved in NDs compared with controls in clinical studies. The 1q21.1 CNVs, rare and large chromosomal microduplications and microdeletions, are detected in many patients with NDs. Phenotypes of duplication and deletion appear at the two ends of the spectrum. Microdeletions are predominant in individuals with schizophrenia (SCZ) and microcephaly, whereas microduplications are predominant in individuals with autism spectrum disorder (ASD) and macrocephaly. However, its complexity hinders the discovery of molecular pathways and phenotypic networks. In this review, we summarize the recent genome-wide association studies (GWASs) that have identified candidate genes positively correlated with 1q21.1 CNVs, which are likely to contribute to abnormal phenotypes in carriers. We discuss the clinical data implicated in the 1q21.1 genetic structure that is strongly associated with neurodevelopmental dysfunctions like cognitive impairment and reduced synaptic plasticity. We further present variations reported in the phenotypic severity, genomic penetrance and inheritance.

scholarly journals Unravelling the Roles of Susceptibility Loci for Autoimmune Diseases in the Post-GWAS Era

Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 377 ◽  
Author(s):  
Jody Ye ◽  
Kathleen Gillespie ◽  
Santiago Rodriguez
Keyword(s):  
Autoimmune Diseases ◽  
Copy Number ◽  
Disease Risk ◽  
Association Studies ◽  
Somatic Mosaicism ◽  
Copy Number Variations ◽  
Genetic Variations ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Environmental Interactions

Although genome-wide association studies (GWAS) have identified several hundred loci associated with autoimmune diseases, their mechanistic insights are still poorly understood. The human genome is more complex than single nucleotide polymorphisms (SNPs) that are interrogated by GWAS arrays. Apart from SNPs, it also comprises genetic variations such as insertions-deletions, copy number variations, and somatic mosaicism. Although previous studies suggest that common copy number variations do not play a major role in autoimmune disease risk, it is possible that certain rare genetic variations with large effect sizes are relevant to autoimmunity. In addition, other layers of regulations such as gene-gene interactions, epigenetic-determinants, gene and environmental interactions also contribute to the heritability of autoimmune diseases. This review focuses on discussing why studying these elements may allow us to gain a more comprehensive understanding of the aetiology of complex autoimmune traits.

scholarly journals Genetics in schizophrenia: where are we and what next?

2010 ◽  
Vol 12 (3) ◽  
pp. 289-303
Keyword(s):  
Copy Number ◽  
Association Studies ◽  
Molecular Genetic ◽  
Copy Number Variations ◽  
Future Research ◽  
Genome Wide Association Studies ◽  
Genetic Studies ◽  
Genome Wide ◽  
Number Variation

Understanding the genetic basis of schizophrenia continues to be major challenge. The research done during the last two decades has provided several candidate genes which unfortunately have not been consistently replicated across or within a population. The recent genome-wide association studies (GWAS) and copy number variation (CNV) studies have provided important evidence suggesting a role of both common and rare large CNVs in schizophrenia genesis. The burden of rare copy number variations appears to be increased in schizophrenia patients. A consistent observation among the GWAS studies is the association with schizophrenia of genetic markers in the major histocompatibility complex (6p22.1)-containing genes including NOTCH4 and histone protein loci. Molecular genetic studies are also demonstrating that there is more overlap between the susceptibility genes for schizophrenia and bipolar disorder than previously suspected. In this review we summarize the major findings of the past decade and suggest areas of future research.

On the analysis of copy-number variations in genome-wide association studies: a translation of the family-based association test

2008 ◽  
Vol 32 (3) ◽  
pp. 273-284 ◽  
Author(s):  
Iuliana Ionita-Laza ◽  
George H. Perry ◽  
Benjamin A. Raby ◽  
Barbara Klanderman ◽  
Charles Lee ◽  
...  
Keyword(s):  
Copy Number ◽  
Association Studies ◽  
Copy Number Variations ◽  
Association Test ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
The Family ◽  
Family Based

scholarly journals Isolated GH deficiency: mutation screening and copy number analysis of HMGA2 and CDK6 genes

2011 ◽  
Vol 165 (4) ◽  
pp. 537-544 ◽  
Author(s):  
Darya Gorbenko Del Blanco ◽  
Laura C G de Graaff ◽  
Dirk Posthouwer ◽  
Theo J Visser ◽  
Anita C S Hokken-Koelega
Keyword(s):  
Candidate Genes ◽  
Copy Number ◽  
Gh Deficiency ◽  
Association Studies ◽  
Normal Population ◽  
Mutation Screening ◽  
Copy Number Variations ◽  
Published Data ◽  
Growth Disorders ◽  
Genome Wide Association Studies

ObjectiveIn most patients, the genetic cause of isolated GH deficiency (IGHD) is unknown. By identifying several genes associated with height variability within the normal population, three separate genome-wide association studies provided new candidate genes for human growth disorders. We selected two of them for genetic screening of our IGHD population.AimWe aimed to determine whether high-mobility group A2 (HMGA2) and cyclin-dependent protein kinase 6 (CDK6) are involved in the pathogenicity of IGHD.MethodsWe directly sequenced coding regions and exon–intron boundaries of the genesHMGA2andCDK6in 105 Caucasian IGHD patients from the Dutch HYPOPIT study. In addition, we developed a new probe set of multiplex ligation-dependent probe amplification for both genes in order to detect copy number variations.ResultsIn one patient with classical IGHD phenotype, we identified a new heterozygous 20 bp deletion in the intronic region ofHMGA2(c.250-29_-9del), which was absent in the databases and healthy controls. Together, with recently published data concerning the 12q14 microdeletion syndrome, where patients with anHMGA2haploinsufficiency had proportionate short stature, this study provides further support of the important role for HMGA2 in growth. InCDK6, we found only known polymorphisms.ConclusionsThis study provides the first report of a deletion in theHMGA2gene that might be related to IGHD. We suggest that this gene is investigated as a second screening in patients with a classical IGHD phenotype in which mutations in classical candidate genes have been excluded.

scholarly journals Trans-ethnic genome-wide meta-analysis of 35,732 cases and 34,424 controls identifies novel genomic cross-ancestry loci contributing to lung cancer susceptibility

2020 ◽  
Author(s):  
Jinyoung Byun ◽  
Younghun Han ◽  
Yafang Li ◽  
Jun Xia ◽  
Xiangjun Xiao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Large Scale ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Cancer Etiology ◽  
Genome Wide ◽  
Meta Analyses

SummaryLung cancer is the leading cause of cancer death worldwide. Genome-wide association studies have revealed genetic risk factors, highlighting the role of smoking, family history, telomere regulation, and DNA damage-repair in lung cancer etiology. Many studies have focused on a single ethnic group to avoid confounding from variability in allele frequencies across populations; however, comprehensive multi-ethnic analyses may identify variants that are more likely to be causal. This large-scale, multi- ethnic meta-analyses identified 28 novel risk loci achieving genome-wide significance. Leading candidates were further studied using single-cell methods for evaluating DNA-damage. DNA-damage promoting activities were confirmed for selected genes by knockdown genes and overexpression studies.

Liver and Statins: A Critical Appraisal of the Evidence

2019 ◽  
Vol 25 (42) ◽  
pp. 5835-5846 ◽  
Author(s):  
Anna Licata ◽  
Antonina Giammanco ◽  
Maria Giovanna Minissale ◽  
Salvatore Pagano ◽  
Salvatore Petta ◽  
...  
Keyword(s):  
Adverse Events ◽  
Association Studies ◽  
Organic Anion ◽  
Genome Wide Association Studies ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Organic Anion Transporting Polypeptide ◽  
Treatment And Prevention ◽  
Genome Wide ◽  
Underlying Mechanisms

Adverse drug reactions (ADRs) represent an important cause of morbidity and mortality worldwide. Statins are a class of drugs whose main adverse effects are drug-induced liver injury (DILI) and myopathy. Some of these may be predictable, due to their pharmacokinetic and pharmacodynamic properties, while others, unfortunately, are idiosyncratic. Genetic factors may also influence patient susceptibility to DILI and myopathy in the case of statins. This review will first discuss the role of statins in cardiovascular disease treatment and prevention and the underlying mechanisms of action. Furthermore, to explore the susceptibility of statin-induced adverse events such as myopathy and hepatotoxicity, it will then focus on the recent Genome-Wide Association Studies (GWAS) concerning the transporter genes, Cytochrome P450 (CYP), organic anion-transporting polypeptide (OATP) and ABCB1 and ABCC1, which seem to play a role in the development of clinically relevant adverse events. Finally, we appraise the evidence for and against the use of statins in metabolic syndrome and in HCV-infected patients, in terms of their safety and efficacy in cardiovascular events.

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