scholarly journals GWAS Links New Variant in Long Non-Coding RNA LINC02006 with Colorectal Cancer Susceptibility

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 465
Author(s):  
Ewa E. Hennig ◽  
Anna Kluska ◽  
Magdalena Piątkowska ◽  
Maria Kulecka ◽  
Aneta Bałabas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Bioinformatic Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Tumor Invasiveness ◽  
Non Coding Rna ◽  
New Variant ◽  
Long Non Coding Rna

Despite great efforts, most of the genetic factors contributing to the risk of colorectal cancer (CRC) remain undetermined. Including small but homogenous populations in genome-wide association studies (GWAS) can help us discover new common risk variants specific to the studied population. In this study, including 465 CRC patients and 1548 controls, a pooled DNA samples-based GWAS was conducted in search of genetic variants associated with CRC in a Polish population. Combined with a new method of selecting single-nucleotide polymorphisms (SNPs) for verification in individual DNA samples, this approach allowed the detection of five new susceptibility loci not previously reported for CRC. The discovered loci were found to explain 10% of the overall risk of developing CRC. The strongest association was observed for rs10935945 in long non-coding RNA LINC02006 (3q25.2). Three other SNPs were also located within genes (rs17575184 in NEGR1, rs11060839 in PIWIL1, rs12935896 in BCAS3), while one was intergenic (rs9927668 at 16p13.2). An expression quantitative trait locus (eQTL) bioinformatic analysis suggested that these polymorphisms may affect transcription factor binding sites. In conclusion, four of the identified variants were located within genes likely involved in tumor invasiveness and metastasis. Therefore, they could possibly be markers of poor prognosis in CRC patients.

scholarly journals Pharmacogenomics of Lithium Response in Bipolar Disorder

2021 ◽  
Vol 14 (4) ◽  
pp. 287
Author(s):  
Courtney M. Vecera ◽  
Gabriel R. Fries ◽  
Lokesh R. Shahani ◽  
Jair C. Soares ◽  
Rodrigo Machado-Vieira
Keyword(s):  
Bipolar Disorder ◽  
Association Studies ◽  
Mood Stabilizer ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Lithium Response ◽  
Genetic Loading ◽  
Long Non Coding Rna

Despite being the most widely studied mood stabilizer, researchers have not confirmed a mechanism for lithium’s therapeutic efficacy in Bipolar Disorder (BD). Pharmacogenomic applications may be clinically useful in the future for identifying lithium-responsive patients and facilitating personalized treatment. Six genome-wide association studies (GWAS) reviewed here present evidence of genetic variations related to lithium responsivity and side effect expression. Variants were found on genes regulating the glutamate system, including GAD-like gene 1 (GADL1) and GRIA2 gene, a mutually-regulated target of lithium. In addition, single nucleotide polymorphisms (SNPs) discovered on SESTD1 may account for lithium’s exceptional ability to permeate cell membranes and mediate autoimmune and renal effects. Studies also corroborated the importance of epigenetics and stress regulation on lithium response, finding variants on long, non-coding RNA genes and associations between response and genetic loading for psychiatric comorbidities. Overall, the precision medicine model of stratifying patients based on phenotype seems to derive genotypic support of a separate clinical subtype of lithium-responsive BD. Results have yet to be expounded upon and should therefore be interpreted with caution.

scholarly journals Polymorphisms of a novel long non-coding RNA RP11-108K3.2 with colorectal cancer susceptibility and their effects on its expression

2019 ◽  
Vol 35 (1) ◽  
pp. 3-9
Author(s):  
Danjie Jiang ◽  
Mingjuan Jin ◽  
Ding Ye ◽  
Yingjun Li ◽  
Fangyuan Jing ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Chinese Populations ◽  
Lncrna Transcript ◽  
Validated Questionnaire ◽  
Non Coding Rna ◽  
Validation Set ◽  
Long Non Coding Rna

Background: RP11-108K3.2 was recently identified as a novel long non-coding RNA (lncRNA) transcript, and several single nucleotide polymorphisms (SNPs) have been identified in its coding region. This study aimed to explore the associations of tagSNPs in RP11-108K3.2 with the risk of colorectal cancer and their effects on its expression. Methods: A total of 821 colorectal cancer cases and 857 healthy controls were enrolled into this two-stage case-control study. Demographic characteristics and lifestyle information were collected by a validated questionnaire. Six tagSNPs were genotyped by using Sequenom MassARRAY platform. A total of 71 additional colorectal cancer cases were recruited, of which the genotypes of potential polymorphisms and the RP11-108K3.2 expression levels were determined. Results: In the discovery set, only the rs2470151 C/T polymorphism was found to have a promising association with the risk of colorectal cancer, and this polymorphism was further replicated in the validation set with a significantly decreased risk of colorectal cancer (adjusted odds ratio 0.73; 95% confidence interval 0.55, 0.97). Combined discovery set and validation set together, this negative association was found both in the heterozygote codominant model and the dominant model. Furthermore, colorectal cancer patients carrying rs2470151 CT/TT genotypes had a marginally lower RNA expression of RP11-108K3.2 than those carrying the CC genotype. Stratified analyses showed the association between rs2470151 and the risk of colorectal cancer were influenced by family history of cancer, smoking, alcohol consumption, and tea drinking. Conclusions: These findings suggest that RP11-108K3.2 rs2470151 had a significant association with the risk of colorectal cancer; this may help to predict the susceptibility of colorectal cancer in Chinese populations.

scholarly journals Four novel polymorphisms in long non-coding RNA HOTTIP are associated with the risk and prognosis of colorectal cancer

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhi Lv ◽  
Qian Xu ◽  
Liping Sun ◽  
Jing Wen ◽  
Xinxin Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Susceptibility ◽  
Human Cancer ◽  
Predictive Biomarkers ◽  
Nucleotide Polymorphisms ◽  
Specific Pcr ◽  
Non Coding Rna ◽  
And Function ◽  
Stratified Analysis ◽  
Long Non Coding Rna

AbstractBackground: The role of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) as an oncogene in varieties of human cancer including colorectal cancer (CRC) has been extensively researched. The expression and function of lncRNAs could be affected by single nucleotide polymorphisms (SNPs), which are associated with cancer susceptibility and prognosis. However, no investigation has focused on the association between HOTTIP SNPs and CRC. The aim of the present study was to explore the association of polymorphisms in the lncRNA HOTTIP gene with CRC risk and prognosis. Methods: A total of 1848 subjects were enrolled in our study, including 884 CRC cases and 964 controls. Genotyping for five HOTTIP tagSNPs (rs3807598, rs17501292, rs2067087, rs17427960, and rs78248039) was performed by applying Kompetitive allele specific PCR (KASP). Results: The results showed three SNPs (rs3807598, rs2067087, and rs17427960) were associated with enhanced CRC risk both in overall and stratified analysis. One polymorphism, rs17501292, could improve the overall survival (OS) of CRC patients in the tumor of ulcerative/invasive-type subgroup. Conclusion: These findings suggest HOTTIP SNPs could potentially be predictive biomarkers for CRC risk and prognosis. The present study provides clues for further exploration of novel lncRNA-based genetic biomarkers to predict CRC susceptibility as well as clinical outcome.

scholarly journals A new GWAS and meta-analysis with 1000Genomes imputation identifies novel risk variants for colorectal cancer

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Nada A. Al-Tassan ◽  
Nicola Whiffin ◽  
Fay J. Hosking ◽  
Claire Palles ◽  
Susan M. Farrington ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Association Studies ◽  
Meta Analysis ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Risk Variants ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Long Non Coding Rna

Abstract Genome-wide association studies (GWAS) of colorectal cancer (CRC) have identified 23 susceptibility loci thus far. Analyses of previously conducted GWAS indicate additional risk loci are yet to be discovered. To identify novel CRC susceptibility loci, we conducted a new GWAS and performed a meta-analysis with five published GWAS (totalling 7,577 cases and 9,979 controls of European ancestry), imputing genotypes utilising the 1000 Genomes Project. The combined analysis identified new, significant associations with CRC at 1p36.2 marked by rs72647484 (minor allele frequency [MAF] = 0.09) near CDC42 and WNT4 (P = 1.21 × 10−8, odds ratio [OR] = 1.21 ) and at 16q24.1 marked by rs16941835 (MAF = 0.21, P = 5.06 × 10−8; OR = 1.15) within the long non-coding RNA (lncRNA) RP11-58A18.1 and ~500 kb from the nearest coding gene FOXL1. Additionally we identified a promising association at 10p13 with rs10904849 intronic to CUBN (MAF = 0.32, P = 7.01 × 10-8; OR = 1.14). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC. Additionally, our analysis further demonstrates that imputation can be used to exploit GWAS data to identify novel disease-causing variants.

scholarly journals Long non-coding RNA polymorphisms on 8q24 are associated with the prognosis of gastric cancer in a Chinese population

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8600 ◽  
Author(s):  
Yangyu Zhang ◽  
Yanhua Wu ◽  
Zhifang Jia ◽  
Donghui Cao ◽  
Na Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Chinese Population ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chinese Populations ◽  
Risk Of Death ◽  
Non Coding Rna ◽  
Increased Risk ◽  
Long Non Coding Rna

Background Gastric cancer (GC) remains the third leading cause of cancer death in China. Although genome-wide association studies have identified the association between several single nucleotide polymorphisms (SNPs) on 8q24 and the risk of GC, the role of these SNPs in the prognosis of GC in Chinese populations has not yet been fully evaluated. Therefore, this study was conducted to explore the association between long non-coding RNA (lncRNA) polymorphisms on 8q24 and the prognosis of GC. Methods We genotyped 726 surgically resected GC patients to explore the association between eight SNPs in the lncRNAs CCAT1 (rs10087719, rs7816475), PCAT1 (rs1026411), PRNCR1 (rs12682421, rs13252298), and CASC8 (rs1562430, rs4871789, rs6983267) transcribed from the 8q24 locus and the prognosis of GC in a Chinese population. Results We found that the patients carrying rs12682421 AA genotypes survived for a shorter time than those with the GG/GA genotype (HR = 1.39, 95% confidence interval (CI) [1.09–1.78]). Compared with the CC/CT genotype, the TT genotype of rs1562430 was associated with an increased risk of death (HR = 1.38, 95% CI [1.06–1.80]). Furthermore, the results also identified the rs1026411 SNP as an independent prognostic factor for poor survival in GC patients. Patients carrying AA/AG variant genotypes had a 36% increased risk of death compared to those carrying the GG genotype (HR = 1.36, 95% CI [1.06–1.74]). These findings suggested that the rs12682421, rs1026411 and rs1562430 SNPs may contribute to the survival of GC and be prognostic markers for GC.

scholarly journals Functional genomics of autoimmune diseases

2021 ◽  
pp. annrheumdis-2019-216794
Author(s):  
Akari Suzuki ◽  
Matteo Maurizio Guerrini ◽  
Kazuhiko Yamamoto
Keyword(s):  
Autoimmune Diseases ◽  
Association Studies ◽  
Linkage Disequilibrium Block ◽  
Causal Variant ◽  
Genome Wide Association Studies ◽  
Coding Region ◽  
Risk Variants ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Long Non Coding Rna

For more than a decade, genome-wide association studies have been applied to autoimmune diseases and have expanded our understanding on the pathogeneses. Genetic risk factors associated with diseases and traits are essentially causative. However, elucidation of the biological mechanism of disease from genetic factors is challenging. In fact, it is difficult to identify the causal variant among multiple variants located on the same haplotype or linkage disequilibrium block and thus the responsible biological genes remain elusive. Recently, multiple studies have revealed that the majority of risk variants locate in the non-coding region of the genome and they are the most likely to regulate gene expression such as quantitative trait loci. Enhancer, promoter and long non-coding RNA appear to be the main target mechanisms of the risk variants. In this review, we discuss functional genetics to challenge these puzzles.

Known colorectal cancer susceptibility loci and survival after colorectal cancer diagnosis.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 394-394 ◽  
Author(s):  
Amanda Phipps ◽  
Xabier Garcia-Albeniz ◽  
Carolyn Hutter ◽  
Emily White ◽  
Charles S. Fuchs ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Fixed Effects ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Cox Proportional Hazards ◽  
Health Study ◽  
Genome Wide Association Studies ◽  
Increased Risk

394 Background: Beyond clinicopathologic stage, there are few established markers of prognosis in colorectal cancer (CRC). Recent genome-wide association studies have identified 17 germline single nucleotide polymorphisms (SNPs) significantly associated with incident CRC. However, it is unclear if these CRC susceptibility SNPs influence survival after CRC diagnosis. Although the functionality of many of these SNPs remains unknown, a few, including rs4939827 in SMAD7, map to genes with plausible biological mechanisms associated with both cancer risk and prognosis. We examined 17 CRC susceptibility SNPs in relation to survival after CRC diagnosis. Methods: We genotyped 2,611 men and women enrolled in five prospective cohort studies who were diagnosed with invasive CRC during study follow-up: the Physicians’ Health Study (N=281), Health Professionals Follow-up Study (N=268), Nurses’ Health Study (N=367), Vitamins and Lifestyle Study (N=281), and the Women’s Health Initiative (N=1414). Analyses were limited to Caucasians with known vital status, cause of death, and survival time. We used Cox proportional hazards regression to assess associations between each SNP and CRC-specific and overall survival in study-specific models adjusted for age, sex, and stage; SNPs were modeled additively to reflect associations per copy of the minor allele. Study-specific results were combined via fixed-effects meta-analysis. Results: The G allele in rs4939827 was associated with poorer CRC-specific survival [hazard ratio (HR)=1.16, p=0.02] and overall survival (HR=1.13, p=0.03) in CRC patients. The A alleles in rs10795668 and in rs4925386 were associated with a 1.14-fold increased risk of overall mortality (both p-values=0.03) but not CRC-specific mortality. Other evaluated SNPs were not associated with survival. Conclusions: Genetic variation in rs4939827 (SMAD7) is associated with CRC-specific and overall survival. These results suggest that SMAD7 may have a role in CRC progression, and provide proof-of-principle that common germline variation may provide prognostic information beyond traditional considerations such as stage.

scholarly journals lncRNA-PCAT1 rs2632159 polymorphism could be a biomarker for colorectal cancer susceptibility

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Ming-li Yang ◽  
Zhe Huang ◽  
Li-na Wu ◽  
Rong Wu ◽  
Han-xi Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Cancer Risk ◽  
Cancer Susceptibility ◽  
Bioinformatic Analysis ◽  
Recessive Model ◽  
Eqtl Analysis ◽  
Nucleotide Polymorphisms ◽  
Colon Cancer Risk

AbstractBackground: Single-nucleotide polymorphisms (SNPs) in lncRNAs could be biomarkers for susceptibility to colorectal cancer (CRC), but the association of PCAT1 polymorphisms and CRC susceptibility is yet to be studied. Methods: Five tagSNPs covering the PCAT1 gene were detected through Kompetitive Allele-Specific PCR among 436 CRC patients and 510 controls. An expression quantitative trait locus (eQTL) bioinformatic analysis was then performed. Results: In the present study, PCAT1 rs2632159 polymorphism increased CRC risk by 1.37-fold and 2.19-fold in the dominant and recessive models, respectively (P=0.040 and 0.041). When the CRC cases were divided into colon cancer and rectal cancer, we found that this polymorphism affected colon cancer risk under the dominant model (P=0.022, OR = 1.51) and affected rectal cancer susceptibility under the recessive model (P=0.009, OR = 3.03). A more pronounced effect was observed in the male subgroup in that PCAT1 rs2632159 SNP increased rectal cancer risk by 3.97-fold (P=0.017). When PCAT1 rs2632159 was present, epistatic effects were observed with rs1902432 and rs785005 (P=0.011 and 0.008, respectively). eQTL analysis showed that rs2632159 could influence binding with the transcription factors EBF, LUN-1, and TCF12. Conclusion:PCAT1 rs2632159 SNP could be a biomarker for CRC risk. And the rs1902432 SNP might only have potential to be a biomarker for colon cancer risk.

scholarly journals Variation rs9929218 and Risk of the Colorectal Cancer and Adenomas: A Meta-analysis

2020 ◽  
Author(s):  
Huiyan Wang ◽  
Dongying Gu ◽  
Miao Yu ◽  
Yanjun Hu ◽  
Zhe Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Colorectal ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Accurate Approximation ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Different Populations

Abstract Backgrounds: Genome-wide association studies (GWAS) have identified multiple common CRC-related (colorectal cancer) SNPs (single nucleotide polymorphisms) including the Cadherin 1(CDH1) rs9929218 may act by increasing the risk of colorectal cancer, colorectal adenoma, or both. These studies, however, reported inconsistent associations. Methods: To derive a more accurate approximation of the connection, we carried out a meta-analysis of 12 published pieces of research including 11,590 controls and 8,192 cases. We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the associations' strength.Results: Meta-analysis implied considerable association between CRC and rs9929218 (OR = 1.21, 95%CI 1.04-1.42 for GG versus AA; OR = 1.22, 95%CI 1.05-1.42 for GG/AG versus AA).In the subgroup analyses, significantly increased risks were found among Europeans.Conclusions: In summary, our meta-analysis studies in different populations confirmed that SNP rs9929218 is significantly associated with CRC risk and that this variant may have a greater impact on Europeans.

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