Mariza de Andrade

..The purpose of this study was to estimate the genetic influences on the initiation of cigarette smoking, the persistence, quantity and age-at-onset of regular cigarette use in Brazilian families...

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

..Other autoantibodies are also associated with RA, specifically rheumatoid factor IgM (RFUW) and anti-cyclic citrullinated peptide (anti-CCP)...

..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...

..Although RFs are a promising approach for genetic data analysis, extensions beyond simple single-nucleotide polymorphism analyses and modifications to improve computational feasibility are needed...

..However, further study is needed to evaluate the power and the feasibility for a whole genome-wide association analysis using the principal components approach...

..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...

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..The heritability of cardiovascular risk factors is expected to differ between populations because of the different distribution of environmental risk factors, as well as the genetic make-up of different human populations...

..Women are also more likely to distribute weight in the abdomen following menopause. We investigated whether genetic loci link with obesity-related phenotypes differently by menopausal status...

..In particular, the relative influences of both genes and the environment may vary in different strata of the population of interest, such as young and old individuals, or males and females...

..Thus, we recommend the Gibbs sampler for imputation purposes because of the ease with which it can be extended to more complicated models, the consistency of the results, and the accountability of the variation due to imputation...

..This analysis demonstrates the applicability of using multivariate linkage analysis and how its use increases the power to detect linkage when genes are involved in the same disease mechanism...

..0. We compared bias and variance in the locus-level copy number data, the concordance amongst regions of copy number gains/deletions and the false-positive rate amongst deleted segments...

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..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...

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..The results of our analysis show that the apolipoprotein E locus has no effect on interindividual variability in systolic blood pressure. We found that the longitudinal measure of heritability of systolic blood pressure is 0.32...

..Data from the Rochester Family Heart Study are used to illustrate the various diagnostic methods and related issues...

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..We report the patterns of ETS exposure history in a clinical cohort of women with newly diagnosed lung cancer...

..No evidence of linkage was found either using the VC longitudinal approach or the regression-based approach, except when all time points were used from Cohorts 1 and 2 and only subjects aged 25 and 75 years were included...

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..As risk assessment for cancer risk is moving toward a multigenic pathway-based approach, future genotype-phenotype correlation studies should also investigate the combined effects of multiple genetic variants...

..They provide the basis for further investigation of the role of these genes in susceptibility and/or progression to clinical disease...

..Renal cell carcinoma accounts for 85% of all renal cancers. No studies have investigated the association between mtDNA content and the risk of renal cell carcinoma...

..Recently, several breast cancer susceptibility loci have been identified through genome-wide association studies. Here we evaluated possible associations between these single nucleotide polymorphisms (SNP) and pancreatic cancer risk...

..07 x 10(-6); P=2.96 x 10(-5)) tagged the PARK10 late-onset PD susceptibility locus. Independent replication across populations will clarify the role of the genomic loci tagged by these SNPs in conferring PD susceptibility...

..The results of this preliminary study suggest that the SNCB locus, though not a susceptibility gene for PD, might modify the age at onset of PD...

..Analyses confirmed a significant inverse association of the UCHL1 S18Y polymorphism with PD overall (OR=0.18, 95% CI=0.05-0.64, p=0.002, recessive model) and in several strata...

..78; 95% CI, 1.28-6.04) or D711D (OR, 2.19; 95% CI, 1.01-4.73). No other significant differences in risk were identified. Minor alleles in DNA repair genes XPF/ERCC4 and XPD/ERCC2 were associated with altered risk for pancreatic cancer...

..We performed linkage analyses to identify genomic regions that influence homocysteine levels in blacks and non-Hispanic whites...

..0001). Recursive partitioning showed no interactions between variants of the SNCAIP gene and variants of the alpha-synuclein gene (SNCA) or the parkin (PARK2) gene...

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..Alpha-synuclein (SNCA) has been one of the most promising susceptibility genes, but large-scale studies have been lacking...

..We hypothesized that common variants in these genes, single nucleotide polymorphisms (SNP), may also influence risk for pancreatic cancer development...

..These findings are consistent with in vitro experiments that revealed tau-mediated fibrillization of alpha-synuclein protein at low concentrations (dose threshold effect)...

..We studied the long-term risk of depressive and anxiety symptoms in women who underwent bilateral oophorectomy before menopause...

..We performed univariate and bivariate linkage analyses to identify genomic regions that influence levels of these traits and exert pleiotropic effects on the traits in hypertensive sibships...

..Single nucleotide polymorphisms (SNP) in the nucleotide excision repair pathway may encode alterations that affect DNA repair function and therefore influence the risk of pancreatic cancer development...

..Functional studies are needed to elucidate the mechanisms of these genes in the development of COPD, lung cancer, or both...

..Single nucleotide polymorphisms (SNP) in regulators of mitosis may promote chromosome missegregation and influence pancreatic cancer and/or survival...

..This population-based study suggests a link between pesticides use and PD that is restricted to men. Pesticides may interact with other genetic or nongenetic factors that are different in men and women...

..We report an analysis exploring relationships among baseline QOL assessments and candidate genetic variations in a large cohort of patients with lung cancer...

..Conclusions: Using our suggested workflow both algorithms performed similarly; however, fewer samples were removed and CRLMM took half the time to run our 854 study samples (4.2 h) compared to Birdseed (8.4 h)...

..Although the association between diabetes mellitus (DM) and pancreatic cancer is well described, temporal patterns of changes in fasting blood glucose (FBG) and body mass index (BMI) before pancreatic cancer diagnosis are not known...

..Investigation of other mitochondrial genetic variations (i.e., nuclear-encoded mitochondrial proteins) would be necessary to elucidate any role of mitochondrial DNA variation in PC...

..No difference in frequency of A1AT deficiency alleles was found between cases and controls, irrespective of the MSI subtype...

..Genetic susceptibility in lung cancer risk has long been recognized but remains ill defined, as does the role of tobacco smoke exposure and chronic obstructive pulmonary disease (COPD)...

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..Although diabetes occurs frequently in pancreatic cancer, the value of new-onset diabetes as a marker of underlying pancreatic cancer is unknown...

..Lung cancer in individuals who have never smoked tobacco products is an increasing medical and public-health issue. We aimed to unravel the genetic basis of lung cancer in never smokers...

..Interferon (IFN) gamma (IFNG) allelic variants are associated with susceptibility to multiple sclerosis (MS) in men but not in women...

..A total of 10 carriers from 180 families were identified, suggesting that BRCA2 mutations account for 6% of moderate and high-risk pancreatic cancer families...

..We did not find an association between CD95L and susceptibility to MS nor CD95 or CD95L and age of onset, disease course and disease severity...

..Our study neither supports the hypothesis that coffee protects against PD nor provides evidence for a pharmacogenetic effect...

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

..Null genetic marker allele frequencies did not differ significantly among cases and controls. We conclude that polymorphisms or haplotypes within the TM gene are not common risk factors for incident VTE...

..We used a clinic-based case-control study specifically designed to address limitations of both cohort and case-control studies to examine the relationship...

..We investigated heritability of these three lipid traits and the extent to which shared effects of genes (pleiotropy) contribute to the additive genetic variation in each trait in hypertensive sibships...

..These findings confirm that UCHL1 is a susceptibility gene for PD and a potential target for disease-modifying therapies...

..Self-reported ancestry may not be a reliable method to reduce the possible impact of population stratification in genetic association studies of outbred populations, such as in the United States...

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..In conclusion, ABI is a modestly heritable trait in AA and NHW hypertensive sibships. Quantitative trait linkage analyses identified several chromosomal regions that may harbor genes influencing ABI...

..Pancreatic adenocarcinoma has been associated with several familial cancer syndromes that also predispose to other malignancies. Younger ages of onset of pancreatic cancer (PC) have been reported in families with these syndromes...

..Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS...

..005) for the 3'(514)*AT(8) allele. We did not detect linkage with MS susceptibility in multiplex families. We did not find a strong association with age at onset, disease course or severity. CTLA-4 is associated with susceptibility to MS...

..9 cM, LOD = 2.06, P = 0.0069). These genomic regions may contain genes that influence interindividual variation in LDL particle size and potentially coronary heart disease susceptibility in African Americans...

..Although linkage association has previously been reported with hypertension, we found no association using the tree-based methodology...

..We aimed to investigate survival patterns in a population-based sample of women who had received an oophorectomy and compare these with women who had not received an oophorectomy...

..1 (P=0.004) and HLA-DQB1*0201-DR3-MICA(*)5.1 (P=0.009) with AA. These results suggest that MICA is both a potential candidate gene and part of an extended HLA haplotype that may contribute to susceptibility to and severity of AA...

..This genomic pathway approach may also offer insights into other complex diseases such as Alzheimer disease, diabetes mellitus, nicotine and alcohol dependence, and several cancers...

..In summary, longitudinal analyses of twin data indicate that genetic factors do not account for a significant proportion of the variation in age-related changes of BMI or lipid and lipoprotein levels...

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..Inasmuch as the chromosome 9 and 17 regions were not detected in the univariate linkage analysis for CAC, multivariate linkage analyses of CAC and genetically correlated risk factors may help localize genes for coronary atherosclerosis...

..Counseling the families of PC patients regarding their risk of cancer remains problematic because little information is available...

..5, and 30 additional ones with lod score >1.7, offer hope for dissecting the genetic architecture of metabolic syndrome with beneficial implications for molecular diagnosis, prognosis, and in potential medical intervention...

..These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney...

..19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies...

..We sought to identify a novel gene for dilated cardiomyopathy (DCM)...

..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...

..671+/-0.110 (P<0.0001). This evidence of strong genetic influence on the susceptibility to leukoaraiosis justifies efforts to localize the responsible genes and characterize the predisposing genetic polymorphisms...

..42; P = 0.003). Our findings are consistent with the hypothesis that PD is a multigenic disorder of the UPS...

..68, p < 0.0001). This newly established historical cohort study provides opportunities to test hypotheses regarding the link between personality and aging, aging-related diseases, and overall mortality...

..Linkage studies are ongoing. The PACGENE Consortium will be a valuable family-based resource that will greatly enhance genetic epidemiology research in pancreatic cancer...

..The methods outlined here make it possible to perform general variance components analyses on time-to-event endpoints, even on large data sets, in a computationally efficient manner...

..Our objective was to describe the effect of participation in SCT screening on participants' risk perceptions, worry, and expectations regarding the accuracy of the screening result...

..Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown...

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..Taken together these data support the assertion that inherited mutations in FANCC can predispose to pancreatic cancer...

..These findings indicate that VR22 has variant(s) which influence Abeta42 and contribute to the previously reported linkage for plasma Abeta42 in LOAD families...

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..Our observations show that EGFR-T790M provides a proliferative advantage with respect to WT EGFR and suggest that the enhanced kinase activity of this mutant is the basis for rare cases of inherited susceptibility to lung cancer...

..Furthermore, only stratified subanalyses detected any genetic association between the V380L common coding polymorphism and PD. We discuss the implication of parkin mutations for Parkinson's disease from this population perspective...

..PLAU_1 is a plausible pathogenic mutation that could act by increasing Abeta42, but additional biological experiments are required to show this definitively...

..Association studies of BDNF variants reveal no associations with Parkinson's disease. Comparisons between substance abusers and controls reveal modest associations. These findings increase interest in this diverse human gene...

..67, CI = 2.21 to 14.60, both of which were located in the 15q24-25.1 locus, than among control subjects. Thus, further research to elucidate causal variants in the 15q24-25.1 locus that are associated with lung cancer is warranted...

..After adjusting for covariates and multiple comparisons, no association between any of the mitochondrial single nucleotide polymorphisms or haplogroups and survival was observed...

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..No new data will be collected for this grant proposal. The application clearly fits the goal of this NHLBI grant program since it will explore new approaches using an existing data set collected through NHLBI support. ..