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Common Variation (common + variation)

Distribution by Scientific Domains

Medical Sciences	55%
Life Sciences	35%
2 Other Domains	10%

Selected Abstracts

Folate metabolism genes, vegetable intake and renal cancer risk in central Europe

INTERNATIONAL JOURNAL OF CANCER, Issue 8 2008
Lee E. Moore
Abstract In a multicenter case-control study of renal cell carcinoma (RCC) conducted in central and eastern Europe, we reported a strong inverse association with high vegetable intake and RCC risk. The odds ratio (OR) for high compared to the lowest tertile of vegetable intake was OR = 0.67; (95% confidence interval (CI): 0.53,0.83; p -trend < 0.001). We hypothesized that variation in key folate metabolism genes may modify this association. Common variation in 5 folate metabolism genes (CBS: Ex9+33C > T (rs234706), Ex13 +41C > T (rs1801181), Ex18 ,391 G > A (rs12613); MTHFR: A222V Ex5+79C > T (rs1801133), Ex8,62A > C (rs1801131); MTR: Ex26 20A > G (rs1805087), MTRR: Ex5+136 T > C (rs161870), and TYMS:IVS2,405 C > T (rs502396), Ex8+157 C > T (rs699517), Ex8+227 A > G (rs2790)) were analyzed among 1,097 RCC cases and 1,555 controls genotyped in this study. Having at least 1 variant T allele of MTHFR A222V was associated with higher RCC risk compared to those with 2 common (CC) alleles (OR = 1.44; 95% CI: 1.17,1.77; p = 0.001). After stratification by tertile of vegetable intake, the higher risk associated with the variant genotype was only observed in the low and medium tertiles (p -trend = 0.001), but not among those in the highest tertile (p -interaction = 0.22). The association remained robust after calculation of the false discovery rate (FDR = 0.05). Of the 3 TYMS SNPs examined, only the TYMS IVS2 ,405 C (rs502396) variant was associated with a significantly lower risk compared to the common genotype (OR = 0.73; 95% CI: 0.57,0.93). Vegetable intake modified the association between all 3 TYMS SNPs and RCC risk (p -interaction < 0.04 for all). In summary, these findings suggest that common variation in MTHFR and TYMS genes may be associated with RCC risk, particularly when vegetable intake is low. © 2007 Wiley-Liss, Inc. [source]

Interaction of the common apolipoprotein C-III (APOC3 -482C > T) and hepatic lipase (LIPC -514C > T) promoter variants affects glucose tolerance in young adults.

ANNALS OF HUMAN GENETICS, Issue 3 2001
European Atherosclerosis Research Study II (EARS-II)
Both hepatic lipase (HL) and apolipoprotein C-III (apoC-III) influence lipid metabolism. Common variation in promoters of both genes, LIPC -514C > T and APOC3 -482C > T, respectively, have been shown to affect plasma lipids and lipoproteins and glucose tolerance. We studied the interaction between both variants on parameters of glucose tolerance and lipid metabolism in 714 healthy young males participating in the second European Atherosclerosis Research Study (EARS-II). Approximately 18% of the subjects were carriers of at least one rare LIPC and APOC3 allele. These subjects exhibited, after fasting and oral fat loading, the highest values of triglyceride-rich lipoproteins, but there was no significant interactive effect on any lipid variable. However, interaction occurred on basal diastolic blood pressure (p=0.036) and, during oral glucose tolerance testing, on peak (p= 0.0065) and area under the curve for glucose (p=0.049), and insulin (p= 0.035). This resulted in the highest diastolic blood pressure and lowest glucose tolerance in carriers of at least one rare allele of both genes. Thus gene:gene interaction between LIPC and APOC3, even in these healthy young males, leads to changes in parameters that are typically characteristic of Syndrome-X. [source]

Common variations in the pretest environment influence genotypic comparisons in models of anxiety

GENES, BRAIN AND BEHAVIOR, Issue 7 2005
G. S. Izídio
The behavioral characterization of rodent strains in different studies and laboratories can provide unreplicable results even when genotypes are kept constant and environmental control is maximized. In the present study, the influence of common laboratory environmental variables and their interaction with genotype on the results of behavioral tests of anxiety/emotionality were investigated. To this end, the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which are known to differ for numerous emotionality-related behaviors, were tested in the open field (OF), elevated plus maze (EPM) and black/white box (BWB), while three environmental factors were systematically controlled and analyzed: (1) the experimenter handling the animal (familiar or unfamiliar); (2) the position of the home cage (top or bottom shelf of the rack) and (3) the behavioral state of the animal immediately before the test (arousal or rest). Experimenter familiarity did not alter the behavior of rats in the OF. Cage position, on the other hand, influenced the behavior in the OF and BWB, with rats housed in top cages appearing less anxious like than those housed in the bottom. In the BWB (but not in the OF), these effects were genotype dependent. Finally, the behavioral state of the animals prior to testing altered the results of the EPM in a strain-dependent manner, with some anxiety-related genotypic differences being found only among rats that were aroused in their home cages. This study showed that common variations in the laboratory environment interact with genotype in behavioral tests of anxiety/emotionality. Recognizing and understanding such variations can help in the design of more effective experiments. [source]

Contribution of genetic factors for melanoma susceptibility in sporadic US melanoma patients

EXPERIMENTAL DERMATOLOGY, Issue 5 2009
M. Laurin Council
To examine the contribution of rare and common variation within known MM genes in sporadic US MM patients, coding regions of known MM susceptibility genes [cyclin-dependent kinase inhibitor 2A (CDKN2A), cyclin-dependent kinase 4, melanocortin 1 receptor (MC1R) and tyrosinase (TYR)] were resequenced in 109,135 MM cases. The significance of variants was examined by comparing their frequencies in 390 cancer-free controls. Potential deleterious mutations in CDKN2A were found in two patients and two others had variants of unknown significance. Cases were more likely than controls to harbour the MC1R,R' variants known or predicted to alter its function (P = 0.002), particularly the R160W variant (P = 0.0035). The associated TYR R402Q variant (rs1126809*A) was found in 29% of cases, similar to what has been described previously. One MM patient with a family history of MM, who had developed other skin cancers, was homozygous for a novel TYR variant (P406L) of unknown significance. Hence, rare variants in TYR may be important risk factors for skin cancer. [source]

Folate metabolism genes, vegetable intake and renal cancer risk in central Europe

Aggregate Earnings and Asset Prices

JOURNAL OF ACCOUNTING RESEARCH, Issue 5 2009
RAY BALL
ABSTRACT A principal-components analysis demonstrates that common earnings factors explain a substantial portion of firm-level earnings variation, implying earnings shocks have substantial systematic components and are not almost fully diversifiable as prior literature has concluded. Furthermore, the principal components of earnings and returns are highly correlated, implying aggregate earnings risks and return risks are related. In contrast to previous studies, the correlation we report between the systematic components of earnings and returns is stable over time. We also show that the earnings factors are priced, in the sense that the sensitivities of securities' returns to the earnings factors explain a significant portion of the cross-sectional variation in returns, even controlling for return risk. This suggests earnings performance is an underlying source of priced risk. Our evidence that the information sets of returns and earnings are jointly determined implies cash flow risk and return risk are not fully separable, and raises the possibility that it is the common variation of earnings and returns that is priced. [source]

Variation in 24 hemostatic genes and associations with non-fatal myocardial infarction and ischemic stroke

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2008
N. L. SMITH
Summary., Background:, Arterial thrombosis involves platelet aggregation and clot formation, yet little is known about the contribution of genetic variation in fibrin-based hemostatic factors to arterial clotting risk. We hypothesized that common variation in 24 coagulation,fibrinolysis genes would contribute to risk of incident myocardial infarction (MI) or ischemic stroke (IS). Methods:, We conducted a population-based, case,control study. Subjects were hypertensive adults and postmenopausal women 30,79 years of age, who sustained a first MI (n = 856) or IS (n = 368) between 1995 and 2002, and controls matched on age, hypertension status, and calendar year (n = 2689). We investigated the risk of MI and IS associated with (i) global variation within each gene as measured by common haplotypes and (ii) individual haplotypes and single nucleotide polymorphisms (SNPs). Significance was assessed using a 0.2 threshold of the false discovery rate q -value, which accounts for multiple testing. Results:, After accounting for multiple testing, global genetic variation in factor (F) VIII was associated with IS risk. Two haplotypes in FVIII and one in FXIIIa1 were significantly associated with increased IS risk (all q -values < 0.2). A plasminogen gene SNP was associated with MI risk. All are new discoveries not previously reported. Another 24 tests had P -values < 0.05 and q -values > 0.2 in MI and IS analyses, 23 of which are new and hypothesis generating. Conclusions:, Apart from the association of FVIII variation with IS, we found little evidence that common variation in the 24 candidate fibrin-based hemostasis genes strongly influences arterial thrombotic risk, but our results cannot rule out small effects. [source]

Haplotype analysis of the PARK 11 gene, GIGYF2, in sporadic Parkinson's disease,

MOVEMENT DISORDERS, Issue 3 2009
Greg T. Sutherland PhD
Abstract Familial Parkinsonism (PARK) genes are strong candidates for conferring susceptibility to common forms of PD. However, most studies to date have provided little evidence that their common variants substantially influence disease risk. Recently, mutations were described in the gene, GIGYF2 (TNRC15), located at the PARK11 locus (2q37.1). Here, we use a haplotype tagging approach to examine common variation in the GIGYF2 gene and PD risk. PD cases (n = 568) and age and gender-matched control subjects (n = 568) were recruited from three specialist movement disorder clinics in Brisbane (Australia) and the Australian electoral roll. Twelve tagging SNPs were assessed in all subjects and haplotype and genotype associations were explored. Overall our findings suggest that common genetic variants of GIGYF2 do not significantly affect sporadic PD risk in Australian Caucasians. © 2008 Movement Disorder Society [source]

Mixture and mixture,process variable experiments for pharmaceutical applications

PHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 4 2004
Christine M. Anderson-Cook
Abstract Many experiments in research and development in the pharmaceutical industry involve mixture components. These are experiments in which the experimental factors are the ingredients of a mixture and the response variable is a function of the relative proportion of each ingredient, not its absolute amount. Thus the mixture ingredients cannot be varied independently. A common variation of the mixture experiment occurs when there are also one or more process factors that can be varied independently of each other and of the mixture components, leading to a mixture,process variable experiment. We discuss the design and analysis of these types of experiments, using tablet formulation as an example. Our objective is to encourage greater utilization of these techniques in pharmaceutical research and development. Copyright © 2004 John Wiley & Sons Ltd. [source]

A Genome-wide Association Study of Autism Reveals a Common Novel Risk Locus at 5p14.1

ANNALS OF HUMAN GENETICS, Issue 3 2009
Deqiong Ma
Summary Although autism is one of the most heritable neuropsychiatric disorders, its underlying genetic architecture has largely eluded description. To comprehensively examine the hypothesis that common variation is important in autism, we performed a genome-wide association study (GWAS) using a discovery dataset of 438 autistic Caucasian families and the Illumina Human 1M beadchip. 96 single nucleotide polymorphisms (SNPs) demonstrated strong association with autism risk (p-value < 0.0001). The validation of the top 96 SNPs was performed using an independent dataset of 487 Caucasian autism families genotyped on the 550K Illumina BeadChip. A novel region on chromosome 5p14.1 showed significance in both the discovery and validation datasets. Joint analysis of all SNPs in this region identified 8 SNPs having improved p-values (3.24E-04 to 3.40E-06) than in either dataset alone. Our findings demonstrate that in addition to multiple rare variations, part of the complex genetic architecture of autism involves common variation. [source]

Association of common variation in glutathione S-transferase genes with premature development of cardiovascular disease in patients with systemic sclerosis

ARTHRITIS & RHEUMATISM, Issue 3 2003
Colin N. A. Palmer PhD
No abstract is available for this article. [source]

Verification that common variation at 2q37.1, 6p25.3, 11q24.1, 15q23, and 19q13.32 influences chronic lymphocytic leukaemia risk

BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2010
Dalemari Crowther-Swanepoel
Summary A recent genome wide association study of chronic lymphocytic leukaemia (CLL) provided evidence that common variation at 2q13 (rs17483466), 2q37.1 (rs13397985), 6p25.3 (rs872071), 11q24.1 (rs735665), 15q23 (rs7176508) and 19q13.32 (rs11083846) affects CLL risk. To verify and further explore the relationship between these variants and CLL risk we genotyped case-control datasets from Spain and Sweden (824 cases, 850 controls). Combined data provided statistically significant support for an association between genotypes at rs13397985, rs872071, rs735665, rs7176508 and rs11083846 and CLL risk. CLL risk increased with increasing numbers of risk alleles (Ptrend = 1·40 × 10,15), consistent with a polygenic model of disease susceptibility. These data validate the relationship between common variation and risk of CLL. [source]

Supernumerary humeral heads of the biceps brachii muscle revisited

CLINICAL ANATOMY, Issue 3 2003
Marc Rodríguez-Niedenführ
Abstract Supernumerary humeral heads of the biceps brachii muscle were found in 27 (15.4%) of 175 cadavers. They were bilateral in five cadavers and unilateral in 22 (8 left, 14 right), giving a total of 32 examples in 350 arms (9.1%). Depending on their origin and location, the supernumerary heads were classified as superior, infero-medial, and infero-lateral humeral heads. Previous studies were reviewed using this classification. The infero-medial humeral head was observed in 31 of 350 (9%) arms and was therefore the most common variation. The superior humeral head was observed in five (1.5%). The infero-lateral humeral head was the least common variation, observed only in one (0.3%) of 350 arms. A biceps brachii with three heads was observed in 27 of 350 (7.7%) arms and with four heads in five (1.4%) arms. Clin. Anat. 16:197,203, 2003. © 2003 Wiley-Liss, Inc. [source]

Association of FcGRIIa with Graves' disease: a potential role for dysregulated autoantibody clearance in disease onset/progression

CLINICAL ENDOCRINOLOGY, Issue 1 2010
Kadija Yesmin
Summary Objective, Although autoantibody production is a key feature of autoimmunity, it is not known whether variation in autoantibody production and clearance pathways is involved in disease susceptibility. The Fc Gamma Receptor IIa (FcGRIIa) molecule is involved in the clearance of autoantibodies and a functional single nucleotide polymorphism (SNP), rs1801274, which has been shown to alter autoantibody clearance, has been associated with a number of autoimmune diseases (AIDs) including systemic lupus erythematosus and type 1 diabetes. This study aimed to determine whether FcGRIIa is associated with Graves' disease (GD) in the UK Caucasian population by Tag SNP screening common polymorphisms within the FcGRIIa region. Design, A case control association study investigating nine Tag SNPs within FcGRIIa, which captured the majority of known common variation within this gene region. Patients, A dataset comprising 2504 UK Caucasian GD patients and 2784 geographically matched controls taken from the 1958 British Birth cohort. Measurements, We used the ,2 -test to investigate association between the Tag SNPs and GD. Results, Association between the rs1801274 (P,= 0·003, OR = 1·12 [95% CI = 1·03,1·22] and rs6427598 (P = 0·012, OR = 0·90 [95% CI = 0·83-0·98]) SNPs and GD was observed. No other SNPs showed association with GD. No associations were seen between any of the SNPs investigated and specific GD clinical phenotypes. Conclusions, This study suggests that variation in FcGRIIa predisposes to GD and further supports the role of FcGRIIa as a susceptibility locus for AIDs in general. [source]

Single nucleotide polymorphism in CTH associated with variation in plasma homocysteine concentration

CLINICAL GENETICS, Issue 6 2004
J Wang
Plasma total homocysteine (tHcy) concentration, an independent risk factor of atherosclerosis, has numerous genetic and environmental determinants. While the thermolabile polymorphism in MTHFR encoding methylenetetrahydrofolate reductase is the best-studied genetic factor associated with variation in plasma tHCy, other candidate genes are being evaluated. Recently, we discovered that cystathioninuria was caused by mutations in the CTH gene encoding cystathionine ,-lyase, an enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway. We also identified a common single nucleotide polymorphism (SNP), namely c.1364G>T (S403I) in exon 12 of CTH. In the current analysis, we studied the association of genotypes of this SNP with plasma tHcy concentrations in 496 Caucasian subjects. CTH 1364T/T homozygotes had significantly higher mean plasma tHcy concentration than subjects with other genotypes, and the effect sizes of CTH and MTHFR genotypes were similar. The findings suggest that common variation in CTH may be a determinant of plasma tHcy concentrations. [source]

Examination of the oral cavity and identification of normal variants

DERMATOLOGIC THERAPY, Issue 3 2002
Carl M. Allen
The purpose of this article is to systematically describe the techniques that are used in examining the oral cavity. A detailed explanation of how each area of the mouth should be examined is provided and common variations of normal anatomy are illustrated. [source]

Common variations in the pretest environment influence genotypic comparisons in models of anxiety

A Haplotype-Based Analysis of the LRP5 Gene in Relation to Osteoporosis Phenotypes in Spanish Postmenopausal Women,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2008
Lídia Agueda
Abstract LRP5 encodes the low-density lipoprotein receptor-related protein 5, a transmembrane protein involved in Wnt signaling. LRP5 is an important regulator of osteoblast growth and differentiation, affecting bone mass in vertebrates. Whether common variations in LRP5 are associated with normal BMD variation or osteoporotic phenotypes is of great relevance. We used a haplotype-based approach to search for common disease-associated variants in LRP5 in a cohort of 964 Spanish postmenopausal women. Twenty-four SNPs were selected, covering the LRP5 region, including the missense changes p.V667M and p.A1330V. The SNPs were genotyped and evaluated for association with BMD at the lumbar spine (LS) or femoral neck (FN) and with osteoporotic fracture, at single SNP and haplotype levels, by regression methods. Association with LS BMD was found for SNP 1, rs312009, located in the 5,-flanking region (p = 0.011, recessive model). SNP 6, rs2508836, in intron 1, was also associated with BMD, both at LS (p = 0.025, additive model) and FN (p = 0.031, recessive model). Two polymorphisms were associated with fracture: SNP 11, rs729635, in intron 1, and SNP 15, rs643892, in intron 5 (p = 0.007 additive model and p = 0.019 recessive model, respectively). Haplotype analyses did not provide additional information, except for haplotype "GC" of the block located at the 3,end of the gene. This haplotype spans intron 22 and the 3, untranslated region and was associated with FN BMD (p = 0.029, one copy of the haplotype versus none). In silico analyses showed that SNP 1 (rs312009) lies in a putative RUNX2 binding site. Electro-mobility shift assays confirmed RUNX2 binding to this site. [source]