VarioWatch: providing large-scale and comprehensive annotations on human genomic variants in the next generation sequencing era

Cheng, Yuchang; Hsiao, Fang-Chih; Yeh, Erh-Chan; Lin, Wan-Jia; Tang, Chengyang; Tseng, Huan-Chin; Wu, Hsing-Tsung; Liu, Chuan-Kun; Chen, Chih‐Cheng; Chen, Yuan-Tsong; Yao, Andrew Chi-Chih

doi:10.1093/nar/gks397

Cited by 38 publications

(24 citation statements)

References 26 publications

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“…These 21 additional SNPs (8 for CRY2 , 11 for CRY1 and 2 for TTC1 ) were selected using Pupasuite [35], Variowatch [36], dbSMR [37] and miRNASNP [38] databases. Table 2 presents all the 48 SNPs that were successfully genotyped in this study and their selection criteria.…”

Section: Methodsmentioning

confidence: 99%

CRY2 Genetic Variants Associate with Dysthymia

et al. 2013

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People with mood disorders often have disruptions in their circadian rhythms. Recent molecular genetics has linked circadian clock genes to mood disorders. Our objective was to study two core circadian clock genes, CRY1 and CRY2 as well as TTC1 that interacts with CRY2, in relation to depressive and anxiety disorders. Of these three genes, 48 single-nucleotide polymorphisms (SNPs) whose selection was based on the linkage disequilibrium and potential functionality were genotyped in 5910 individuals from a nationwide population-based sample. The diagnoses of major depressive disorder, dysthymia and anxiety disorders were assessed with a structured interview (M-CIDI). In addition, the participants filled in self-report questionnaires on depressive and anxiety symptoms. Logistic and linear regression models were used to analyze the associations of the SNPs with the phenotypes. Four CRY2 genetic variants (rs10838524, rs7121611, rs7945565, rs1401419) associated significantly with dysthymia (false discovery rate q<0.05). This finding together with earlier CRY2 associations with winter depression and with bipolar type 1 disorder supports the view that CRY2 gene has a role in mood disorders.

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Section: Methodsmentioning

confidence: 99%

CRY2 Genetic Variants Associate with Dysthymia

et al. 2013

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“…In addition to the aforementioned tag-SNPs, 22 potentially functional variants in CRY1 (12 variants) and CRY2 (10 variants) were included in the genotyping multiplexes. These additional SNPs were selected using Pupasuite (Conde et al, 2006), Variowatch (Cheng et al, 2012) and dbSMR (Hariharan et al, 2009) databases. See Table 1 for the altogether 42 selected SNPs.…”

Section: Gene and Snp Selectionmentioning

confidence: 99%

CRY1 and CRY2 genetic variants in seasonality: A longitudinal and cross-sectional study

Kovanen

Donner

Kaunisto

et al. 2016

Psychiatry Research

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Cryptochromes are key components of the circadian clocks that generate and maintain seasonal variations. The aim of our study was to analyze the associations of CRY1 and CRY2 genetic variants with the problematicity of seasonal variations, and whether the problematicity of seasonal variations changed during the follow-up of 11 years. Altogether 21 CRY1 and 16 CRY2 single-nucleotide polymorphisms (SNPs) were genotyped and analyzed in 5910 individuals from a Finnish nationwide population-based sample who had filled in the self-report on the seasonal variations in mood and behavior in the year 2000. In the year 2011, 3356 of these individuals filled in the same self-report on the seasonal variations in mood and behavior. Regression models were used to test whether any of the SNPs associated with the problematicity of seasonal variations or with a change in the problematicity from 2000 to 2011. In the longitudinal analysis, CRY2 SNP rs61884508 was protective from worsening of problematicity of seasonal variations. In the cross-sectional analysis, CRY2 SNP rs72902437 showed evidence of association with problematicity of seasonal variations, as did SNP rs1554338 (in the MAPK8IP1 and downstream of CRY2).

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“…However, no SNP was found highly linked with it, indicating the unique role of rs3764482 in the locus. The potential function of rs3764482 was primarily explored in silico, with multiple bioinformatics tools and algorithms including ANNOVAR, SIFT, PolyPhen2, and Vario Watch . The ANNOVAR software gave the basic information about this variant.…”

Section: Methodsmentioning

confidence: 99%

A low‐frequency variant in SMAD7 modulates TGF‐β signaling and confers risk for colorectal cancer in Chinese population

Zou

Zhou

et al. 2017

Molecular Carcinogenesis

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The TGF-β pathway plays an essential role in regulating cell proliferation and differentiation. GWASs and candidate approaches have identified a battery of genetic variants in the TGF-β pathway contributing to colorectal cancer (CRC). However, most of the significant variants are common variants and their functions remain ambiguous. To identify causal variants with low-frequency in the TGF-β pathway contributing to CRC susceptibility in Chinese population, we performed targeted sequencing of 12 key genes in TGF-β signaling in CRC patients followed by a two-stage case-control study with a total of 5109 cases and 5169 controls. Bioinformatic annotations and biochemical experiments were applied to reveal the potential functions of significant variants. Seven low-frequency genetic variants were captured through targeted sequencing. The two stage association studies showed that missense variant rs3764482 (c. 83C>T; p. S28F) in the gene SMAD7 was consistently and significantly associated with CRC risk. Compared with the wild type, the ORs for variant allele were 1.37 (95%CI: 1.10-1.70, P = 0.005), 1.55 (95%CI: 1.30-1.86, P = 1.15 × 10 ), and 1.48 (1.29-1.70, P = 2.44 × 10 ) in stage 1, stage 2, and the combined analyses, respectively. Functional annotations revealed that the minor allele T of rs3764482 was more effective than the major allele C in blocking the TGF-β signaling and inhibiting the phosphorylation of receptor-regulated SMADs (R-SMADs). In conclusion, low-frequency coding variant rs3764482 in SMAD7 is associated with CRC risk in Chinese population. The rs3764482 variant may block the TGF-β signaling via impeding the activation of downstream genes, leading to cancer cell proliferation, thus contributing to CRC pathogenesis.

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VarioWatch: providing large-scale and comprehensive annotations on human genomic variants in the next generation sequencing era

Cited by 38 publications

References 26 publications

CRY2 Genetic Variants Associate with Dysthymia

CRY2 Genetic Variants Associate with Dysthymia

CRY1 and CRY2 genetic variants in seasonality: A longitudinal and cross-sectional study

A low‐frequency variant in SMAD7 modulates TGF‐β signaling and confers risk for colorectal cancer in Chinese population

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