Brooke L Fridley

..We will illustrate the utility of this multivariate model for cytotoxicity and genomic data collected on the Coriell Human Variation Panel for the class of anti-purine metabolites (6-mercaptopurine and 6-thioguanine)...

..Further research is required to extend and modify this integrative modeling framework to increase computational efficiency to best capitalize on the wealth of information available across multiple genomic data types...

..Gene set analysis (GSA) overcomes this limitation by assessing overall evidence for association of a phenotype with all measured variation in a set of genes...

..The answers to Problem 3 were requested and known to the authors...

..We illustrate the use of this method through a genome-wide linkage study of colorectal cancer, and a genome-wide association study of colorectal polyps...

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..This paper provides an overview of GSA, highlighting the key challenges, potential solutions, and directions for ongoing research...

..13). In summary, the application of the BLVM allows for the systematic integration of multiple SNP "features" for the prioritization of loci for fine-mapping or functional studies, taking into account the uncertainty in ranking...

..Application of such methods to pharmacogenomic studies may enable the detection of more subtle effects of multiple genes in the same pathway that may be missed by assessing each gene individually...

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..This limited study involving four regions indicates that, contrary to expectations, multiple imputations may not be necessary...

..However, the SNPs identified from these GWAS are not necessarily the functional variants. Therefore, the next phase in GWAS will involve the refining of these putative loci...

..The method is illustrated using the Genetic Analysis Workshop simulated data...

..These results exemplify the utility of imputation in candidate gene studies and lend evidence to a role of cell cycle genes in ovarian cancer etiology, suggest a reduced set of SNPs to target in additional cases and controls...

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..Our findings indicate that two common genetic polymorphisms in the aromatase gene CYP19 vary the response of breast cancer patients to aromatase inhibitors...

..Relying on a significant genotype tests using a log-additive model would have excluded 57% of the non-replicated and none of the replicated loci, while use of other SNP features and clustering might have missed true associations...

..We previously identified a panel of genes associated with outcome of ovarian cancer. The purpose of the current study was to assess whether variants in these genes correlated with ovarian cancer risk...

..We now examine the hypothesis that inherited alterations in TCEAL7 play a role in the etiology of ovarian cancer...

..10). These results indicate that the SNPs studied here are not related to risk of this gynecologic malignancy and that the site-specific nature of 8q24.21.a associations may not include ovarian cancer...

..11, 95% CI: 1.00-1.23, P = 0.04). These findings are consistent with prior studies implicating these genes in carcinogenesis and suggest that this collection of variants is worthy of follow-up in additional studies...

..We aimed to perform a more comprehensive assessment of CTLA4 genetic variation in PBC using a haplotype-tagging based approach...

..Our proposed GS-eQTL method effectively addresses the multiple testing limitations in eQTL studies and provides biological context for SNP-expression associations...

..Genetic variation in proteasome subunits could influence both proteasome function and response to drug therapy...

..These studies have identified novel candidate genes that may contribute to variation in response to MPA therapy and, as a result, may help make it possible to move toward more highly individualized MPA-based immunosuppressive therapy...

..Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development...

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..Invasive ovarian cancer is a significant cause of gynecologic cancer mortality...

..Often these methods do not explicitly model the information regarding the linkage disequilibrium (LD) between SNPs. Furthermore, many methods shrink the SNP effects towards zero, rather than to an unknown latent gene-level effect...

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..16-6.66, P=4.7×10(-12) to 2.2×10(-8)) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P=0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA...

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..4 × 10(-10), R = -0.376). The thiopurine cellular circulation and genetic polymorphisms for genes encoding the proteins involved should be incorporated into future studies of thiopurine drug therapy and effect...

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..The authors' observations are consistent with a recent report that the inherited glioma risk variants in chromosome regions 9p21.3 and 20q13.3 may modify the inverse association of allergy and glioma...

..We also applied all of the considered GSA methods to data from a pharmacogenomic study of cisplatin, and obtained evidence suggesting that the glutathione metabolism GS is associated with cisplatin drug response...

..02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated...

..Overexpression of mitotic kinases has been associated with prognosis, histologic grade, and clinical stage in ovarian cancer, but the relationship between inherited variation in these genes and ovarian cancer risk has not been well defined...

..Inhibitors of kappaB (IkappaB) prevent NF-kappaB activation by sequestering NF-kappaB proteins in the cytoplasm until IkappaB proteins are phosphorylated and degraded...

..However, in both situations, none of the imputation-based tests provide the same level of evidence of association as the complete data at SNPs strongly associated with disease...

..No studies of ovarian cancer have been reported to date...

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..Our studies suggest that functionally significant variant sequence in the human PNMT gene might contribute to individual variation in levels of circulating epinephrine during exercise...

..40). Although CNVs that were not well-covered by the Illumina 610 quad array merit investigation, these data suggest no association between inherited CNVs and survival after ovarian cancer...

..Overall, our findings identify FKBP51 as a negative regulator of the Akt pathway, with potentially important implications for cancer etiology and response to chemotherapy...

..In summary, we conclude, as have other published reports, that normalization methods play an important role in the linkage results, and that some significant linkage signals might be due to a specific normalization method...

..Nonsynonymous coding single nucleotide polymorphisms (nsSNPs) in complement component 3 (C3) alter the risk of age-related macular degeneration (AMD). This was a study of the effect of haplotypes across C3 on AMD risk...

..The aims of this study were to (i) compare the prevalence of IBS in case-relatives with control-relatives, and (ii) determine whether gender, relationship, predominant symptom, and environmental risk factors affect familial aggregation...

..Studies performed with LCLs can help to identify novel biomarkers that might contribute to variation in response to radiation therapy and enhance our understanding of mechanisms underlying that variation...

..Understanding the mechanism underlying this association will provide insight into the genetics of breast tissue composition...

..1×10(-4)) among all cases combined. As the products of these genes are known to affect induction, trafficking, or immunosuppressive function of Tregs, these results suggest the need for follow-up phenotypic studies...

..e., whether a SNP or haplotype is responsible); unfortunately, this is often unknown at the time of SNP selection. Additional evaluations using empirical and simulated data are needed...

..If these observations are validated in future clinical studies, this SNP signal might represent a potential biomarker for risk of acetaminophen hepatotoxicity. The mechanisms responsible for this association remain unclear...

..These observations may help us to understand individual variation in the regulation of BHMT in the human liver and its possible relationship to variation in methylation...

..These results support the use of genome-wide association analyses to identify novel genes influencing antihypertensive drug responses...

..Recent reports support an association between chronic inflammation and progression to pancreatic cancer (PC)...

..Uric acid is heritable and associated with hypertension and insulin resistance. We sought to identify genomic regions influencing serum uric acid in families in which two or more siblings had hypertension...

..The purpose of this study was to determine whether common variation in the 10 human toll-like receptors (TLRs) alters the risk of AMD...

..However, the abundance of associations around 128 Mb on chromosome 8 could mask the appearance of a weaker, but important, association elsewhere on 8q24...

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..To investigate the association between 347 single-nucleotide polymorphisms within candidate genes of the tumor necrosis factor, interleukin 1 and interleukin 6 families with neutrophil count...

..77, P = 2.6 × 10(-9)). These observations generate hypotheses concerning the possible mechanisms by which specific SNPs (or alterations in linkage disequilibrium with such SNPs) are associated with glioma development...

..We conclude that variation in the genes encoding p50 and c-Rel may play a role in NF-kappaB-related transcription of FAS, IRF1, and CD40...

..Thus, host genetic variation may contribute to phenotypic diversity among myeloproliferative disorders, including in the presence of a shared disease allele...

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..To assess participation bias in the assembly of a specimen repository for genetic studies and to examine the association of participation with outcome within the Olmsted County myocardial infarction (MI) cohort...

..These group contributions exhibit the value of framing genetic problems in terms of model selection, and highlight the impact of variable selection for gene mapping...

..This study investigates the role of DPYS sequence variations in individuals with unexplained molecular basis of altered uracil catabolism...

..This study investigates the possible role of UPB1 genetic variations in the regulation of the uracil catabolic pathway in individuals presenting with a deficient uracil breath test (13C-UraBT) despite normal DPD enzyme activity...