The Experts below are selected from a list of 252 Experts worldwide ranked by ideXlab platform

John Attia - One of the best experts on this subject based on the ideXlab platform.

  • the choice of a genetic model in the meta analysis of Molecular Association studies
    International Journal of Epidemiology, 2005
    Co-Authors: Cosetta Minelli, Ammarin Thakkinstian, John R Thompson, Keith Y R Abrams, John Attia
    Abstract:

    BACKGROUND: To evaluate gene-disease Associations, genetic epidemiologists collect information on the disease risk in subjects with different genotypes (for a bi-allelic polymorphism: gg, Gg, GG). Meta-analyses of such studies usually reduce the problem to a single comparison, either by performing two separate pairwise comparisons or by assuming a specific underlying genetic model (recessive, co-dominant, dominant). A biological justification for the choice of the genetic model is seldom available. METHODS: We present a genetic model-free approach, which does not assume that the underlying genetic model is known in advance but still makes use of the information available on all genotypes. The approach uses OR(GG), the odds ratio between the homozygous genotypes, to capture the magnitude of the genetic effect, and lambda, the heterozygote log odds ratio as a proportion of the homozygote log odds ratio, to capture the genetic mode of inheritance. The analysis assumes that the same unknown genetic model, i.e. the same lambda, applies in all studies, and this is investigated graphically. The approach is illustrated using five examples of published meta-analyses. RESULTS: Analyses based on specific genetic models can produce misleading estimates of the odds ratios when an inappropriate model is assumed. The genetic model-free approach gives appropriately wider confidence intervals than genetic model-based analyses because it allows for uncertainty about the genetic model. In terms of assessment of model fit, it performs at least as well as a bivariate pairwise analysis in our examples. CONCLUSIONS: The genetic model-free approach offers a unified approach that efficiently estimates the genetic effect and the underlying genetic model. A bivariate pairwise analysis should be used if the assumption of a common genetic model across studies is in doubt.

  • a method for meta analysis of Molecular Association studies
    Statistics in Medicine, 2005
    Co-Authors: Ammarin Thakkinstian, Catherine Deste, Patrick Mcelduff, David L Duffy, John Attia
    Abstract:

    Although population-based Molecular Association studies are becoming increasingly popular, methodology for the meta-analysis of these studies has been neglected, particularly with regard to two issues: testing Hardy-Weinberg equilibrium (HWE), and pooling results in a manner that reflects a biological model of gene effect. We propose a process for pooling results from population-based Molecular Association studies which consists of the following steps: (1) checking HWE using chi-square goodness of fit; we suggest performing sensitivity analysis with and without studies that are in HWE. (2) Heterogeneity is then checked, and if present, possible causes are explored. (3) If no heterogeneity is present, regression analysis is used to pool data and to determine the gene effect. (4) If there is a significant gene effect, pairwise group differences are analysed and these data are allowed to 'dictate' the best genetic model. (5) Data may then be pooled using this model. This method is easily performed using standard software, and has the advantage of not assuming an a priori genetic model.

  • meta analysis of Molecular Association studies vitamin d receptor gene polymorphisms and bmd as a case study
    Journal of Bone and Mineral Research, 2003
    Co-Authors: Ammarin Thakkinstian, Catherine Deste, John A Eisman, Tuan V Nguyen, John Attia
    Abstract:

    With the rise of Molecular and genetic epidemiology, Molecular Association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the Association of the vitamin D receptor (VDR) gene polymorphisms and BMD. We also highlight methodological issues that need to be resolved. Introduction: With the rise of Molecular and genetic epidemiology, Molecular Association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the Association of vitamin D receptor (VDR) gene polymorphisms and BMD/osteoporosis and highlights methodological issues. Materials and Methods: Studies published from 1994 to 2001 were identified through Medline using PubMed software. The reference lists of the articles retrieved were also reviewed. Where eligible papers had insufficient information, we contacted authors by mail (up to three mailings) for additional information. Any observational study, which tested the Association between VDR BsmI genotypes and either BMD or osteoporosis at the femoral neck or spine in adult women, was included in the review. Data were extracted independently by two reviewers (AT and JA) using a standardized data extraction form. Results: The B allele was significantly associated with BMD at the spine; it seemed to follow a recessive model, with the BB genotype having lower BMD than Bb/bb genotypes at baseline, which led to greater bone mineral loss over time. Highlighted methodological lessons included the need to check Hardy-Weinberg equilibrium and the importance of exploring heterogeneity, pooling data in a manner that is sensitive to genetic models, and avoiding multiple comparisons. Conclusion: With the proliferation of Molecular Association studies, there will be an increased need to quantify the magnitude of the risk associated with genetic polymorphisms. This will likely entail meta-analytic methods, and this meta-analysis highlights some of the methodological issues that will need to be resolved.

  • Meta‐Analysis of Molecular Association Studies: Vitamin D Receptor Gene Polymorphisms and BMD as a Case Study
    Journal of Bone and Mineral Research, 2003
    Co-Authors: Ammarin Thakkinstian, John A Eisman, Tuan V Nguyen, Catherine D'este, John Attia
    Abstract:

    With the rise of Molecular and genetic epidemiology, Molecular Association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the Association of the vitamin D receptor (VDR) gene polymorphisms and BMD. We also highlight methodological issues that need to be resolved. Introduction: With the rise of Molecular and genetic epidemiology, Molecular Association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the Association of vitamin D receptor (VDR) gene polymorphisms and BMD/osteoporosis and highlights methodological issues. Materials and Methods: Studies published from 1994 to 2001 were identified through Medline using PubMed software. The reference lists of the articles retrieved were also reviewed. Where eligible papers had insufficient information, we contacted authors by mail (up to three mailings) for additional information. Any observational study, which tested the Association between VDR BsmI genotypes and either BMD or osteoporosis at the femoral neck or spine in adult women, was included in the review. Data were extracted independently by two reviewers (AT and JA) using a standardized data extraction form. Results: The B allele was significantly associated with BMD at the spine; it seemed to follow a recessive model, with the BB genotype having lower BMD than Bb/bb genotypes at baseline, which led to greater bone mineral loss over time. Highlighted methodological lessons included the need to check Hardy-Weinberg equilibrium and the importance of exploring heterogeneity, pooling data in a manner that is sensitive to genetic models, and avoiding multiple comparisons. Conclusion: With the proliferation of Molecular Association studies, there will be an increased need to quantify the magnitude of the risk associated with genetic polymorphisms. This will likely entail meta-analytic methods, and this meta-analysis highlights some of the methodological issues that will need to be resolved.

  • meta analyses of Molecular Association studies methodologic lessons for genetic epidemiology
    Journal of Clinical Epidemiology, 2003
    Co-Authors: John Attia, Ammarin Thakkinstian, Catherine Deste
    Abstract:

    Meta-analyses of population-based Molecular Association studies have become increasingly common over the last 10 years, but little attention has been paid to methodology. In addition to the traditional considerations pertinent to any meta-analysis, there are genetic issues particular to Molecular Association studies: checking Hardy-Weinberg equilibrium, handling data from more than two groups while avoiding multiple comparisons, and pooling data in a way that is sensitive to genetic models. We systematically reviewed all meta-analyses of Molecular Association studies identified via MEDLINE. Of a total of 37 studies, eight (22%) described the search terms. Nineteen (51%) did not state inclusion or exclusion criteria. Heterogeneity was assessed in 28 (76%), but only 7 of 37 (19%) studies checked for publication bias. Nine (24%) studies assessed the goodness-of-fit of Hardy-Weinberg equilibrium, and eight (22%) gave any biological rationale to justify the choice of genetic model used for pooling. There is a need for greater communication between epidemiologists and geneticists to develop methods appropriate to this area.

G. A. Al’per - One of the best experts on this subject based on the ideXlab platform.

Ammarin Thakkinstian - One of the best experts on this subject based on the ideXlab platform.

  • the choice of a genetic model in the meta analysis of Molecular Association studies
    International Journal of Epidemiology, 2005
    Co-Authors: Cosetta Minelli, Ammarin Thakkinstian, John R Thompson, Keith Y R Abrams, John Attia
    Abstract:

    BACKGROUND: To evaluate gene-disease Associations, genetic epidemiologists collect information on the disease risk in subjects with different genotypes (for a bi-allelic polymorphism: gg, Gg, GG). Meta-analyses of such studies usually reduce the problem to a single comparison, either by performing two separate pairwise comparisons or by assuming a specific underlying genetic model (recessive, co-dominant, dominant). A biological justification for the choice of the genetic model is seldom available. METHODS: We present a genetic model-free approach, which does not assume that the underlying genetic model is known in advance but still makes use of the information available on all genotypes. The approach uses OR(GG), the odds ratio between the homozygous genotypes, to capture the magnitude of the genetic effect, and lambda, the heterozygote log odds ratio as a proportion of the homozygote log odds ratio, to capture the genetic mode of inheritance. The analysis assumes that the same unknown genetic model, i.e. the same lambda, applies in all studies, and this is investigated graphically. The approach is illustrated using five examples of published meta-analyses. RESULTS: Analyses based on specific genetic models can produce misleading estimates of the odds ratios when an inappropriate model is assumed. The genetic model-free approach gives appropriately wider confidence intervals than genetic model-based analyses because it allows for uncertainty about the genetic model. In terms of assessment of model fit, it performs at least as well as a bivariate pairwise analysis in our examples. CONCLUSIONS: The genetic model-free approach offers a unified approach that efficiently estimates the genetic effect and the underlying genetic model. A bivariate pairwise analysis should be used if the assumption of a common genetic model across studies is in doubt.

  • a method for meta analysis of Molecular Association studies
    Statistics in Medicine, 2005
    Co-Authors: Ammarin Thakkinstian, Catherine Deste, Patrick Mcelduff, David L Duffy, John Attia
    Abstract:

    Although population-based Molecular Association studies are becoming increasingly popular, methodology for the meta-analysis of these studies has been neglected, particularly with regard to two issues: testing Hardy-Weinberg equilibrium (HWE), and pooling results in a manner that reflects a biological model of gene effect. We propose a process for pooling results from population-based Molecular Association studies which consists of the following steps: (1) checking HWE using chi-square goodness of fit; we suggest performing sensitivity analysis with and without studies that are in HWE. (2) Heterogeneity is then checked, and if present, possible causes are explored. (3) If no heterogeneity is present, regression analysis is used to pool data and to determine the gene effect. (4) If there is a significant gene effect, pairwise group differences are analysed and these data are allowed to 'dictate' the best genetic model. (5) Data may then be pooled using this model. This method is easily performed using standard software, and has the advantage of not assuming an a priori genetic model.

  • meta analysis of Molecular Association studies vitamin d receptor gene polymorphisms and bmd as a case study
    Journal of Bone and Mineral Research, 2003
    Co-Authors: Ammarin Thakkinstian, Catherine Deste, John A Eisman, Tuan V Nguyen, John Attia
    Abstract:

    With the rise of Molecular and genetic epidemiology, Molecular Association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the Association of the vitamin D receptor (VDR) gene polymorphisms and BMD. We also highlight methodological issues that need to be resolved. Introduction: With the rise of Molecular and genetic epidemiology, Molecular Association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the Association of vitamin D receptor (VDR) gene polymorphisms and BMD/osteoporosis and highlights methodological issues. Materials and Methods: Studies published from 1994 to 2001 were identified through Medline using PubMed software. The reference lists of the articles retrieved were also reviewed. Where eligible papers had insufficient information, we contacted authors by mail (up to three mailings) for additional information. Any observational study, which tested the Association between VDR BsmI genotypes and either BMD or osteoporosis at the femoral neck or spine in adult women, was included in the review. Data were extracted independently by two reviewers (AT and JA) using a standardized data extraction form. Results: The B allele was significantly associated with BMD at the spine; it seemed to follow a recessive model, with the BB genotype having lower BMD than Bb/bb genotypes at baseline, which led to greater bone mineral loss over time. Highlighted methodological lessons included the need to check Hardy-Weinberg equilibrium and the importance of exploring heterogeneity, pooling data in a manner that is sensitive to genetic models, and avoiding multiple comparisons. Conclusion: With the proliferation of Molecular Association studies, there will be an increased need to quantify the magnitude of the risk associated with genetic polymorphisms. This will likely entail meta-analytic methods, and this meta-analysis highlights some of the methodological issues that will need to be resolved.

  • Meta‐Analysis of Molecular Association Studies: Vitamin D Receptor Gene Polymorphisms and BMD as a Case Study
    Journal of Bone and Mineral Research, 2003
    Co-Authors: Ammarin Thakkinstian, John A Eisman, Tuan V Nguyen, Catherine D'este, John Attia
    Abstract:

    With the rise of Molecular and genetic epidemiology, Molecular Association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the Association of the vitamin D receptor (VDR) gene polymorphisms and BMD. We also highlight methodological issues that need to be resolved. Introduction: With the rise of Molecular and genetic epidemiology, Molecular Association studies are increasingly common; however, meta-analysis of these studies has been a neglected area. This study performed a meta-analysis of the Association of vitamin D receptor (VDR) gene polymorphisms and BMD/osteoporosis and highlights methodological issues. Materials and Methods: Studies published from 1994 to 2001 were identified through Medline using PubMed software. The reference lists of the articles retrieved were also reviewed. Where eligible papers had insufficient information, we contacted authors by mail (up to three mailings) for additional information. Any observational study, which tested the Association between VDR BsmI genotypes and either BMD or osteoporosis at the femoral neck or spine in adult women, was included in the review. Data were extracted independently by two reviewers (AT and JA) using a standardized data extraction form. Results: The B allele was significantly associated with BMD at the spine; it seemed to follow a recessive model, with the BB genotype having lower BMD than Bb/bb genotypes at baseline, which led to greater bone mineral loss over time. Highlighted methodological lessons included the need to check Hardy-Weinberg equilibrium and the importance of exploring heterogeneity, pooling data in a manner that is sensitive to genetic models, and avoiding multiple comparisons. Conclusion: With the proliferation of Molecular Association studies, there will be an increased need to quantify the magnitude of the risk associated with genetic polymorphisms. This will likely entail meta-analytic methods, and this meta-analysis highlights some of the methodological issues that will need to be resolved.

  • meta analyses of Molecular Association studies methodologic lessons for genetic epidemiology
    Journal of Clinical Epidemiology, 2003
    Co-Authors: John Attia, Ammarin Thakkinstian, Catherine Deste
    Abstract:

    Meta-analyses of population-based Molecular Association studies have become increasingly common over the last 10 years, but little attention has been paid to methodology. In addition to the traditional considerations pertinent to any meta-analysis, there are genetic issues particular to Molecular Association studies: checking Hardy-Weinberg equilibrium, handling data from more than two groups while avoiding multiple comparisons, and pooling data in a way that is sensitive to genetic models. We systematically reviewed all meta-analyses of Molecular Association studies identified via MEDLINE. Of a total of 37 studies, eight (22%) described the search terms. Nineteen (51%) did not state inclusion or exclusion criteria. Heterogeneity was assessed in 28 (76%), but only 7 of 37 (19%) studies checked for publication bias. Nine (24%) studies assessed the goodness-of-fit of Hardy-Weinberg equilibrium, and eight (22%) gave any biological rationale to justify the choice of genetic model used for pooling. There is a need for greater communication between epidemiologists and geneticists to develop methods appropriate to this area.

Fumihiko Tanaka - One of the best experts on this subject based on the ideXlab platform.

  • Theory of Molecular Association and Thermoreversible Gelation
    Molecular Gels, 2020
    Co-Authors: Fumihiko Tanaka
    Abstract:

    We have presented an outline of a theoretical scheme to study Molecular Association and thermoreversible gelation in polymer solutions and mixtures. The effects of the thermodynamic nature of the sol/gel transition, interference with phase separation, structure of the network junctions, path connectivity in the network have been studied on the basis of the multiple tree statistics combined with classical lattice-theoretical polymer solutions. This chapter has focused mainly on the gelation of water-soluble associating polymers driven by hydrophobic aggregation, but applications to other many types of gels, such as those driven by hydrogen bonds, micro-crystallization, helix formation, etc. are possible.We close in hoping that, after reading this chapter, readers will try to find phase diagrams of their own systems in the framework of this theory.

  • Theoretical Study of Molecular Association and Thermoreversible Gelation in Polymers
    Polymer Journal, 2002
    Co-Authors: Fumihiko Tanaka
    Abstract:

    This paper reviews our recent theoretical studies of Molecular Association and thermoreversible gelation in polymer solutions and blends. We first classify fundamental types of Association, and propose their static and dynamic characterization. We then develope general theory of associating polymers to study phase transitions induced by Molecular Association. These transitions include macro- and microphase separation, micellization, hydration, thermoreversible gelation and liquid-crystalization. As for the origin of associative forces, we focus on hydrogen bonding and hydrophobic aggregation. Detailed study on thermoreversible gelation with multiple cross-link junctions is presented. Paying special attention to the multiplicity and sequence length of the network junctions, we derive phase diagrams with coexisting gelation and phase separation, and compare them with experimental data. Local and global structures of the gel networks are studied from Molecular point of view. The theory is applied to more complex thermoreversible gels such as binary networks (interpenetrating networks, alternating networks and randomely mixed networks), hydrated networks with high-temperature gelation, gelation strongly coupled to polymer conformational transitions such as coil-to-helix transition. To study dynamics of thermoreversible gels, a simple transient network model is introduced, and creation and annihilation of junctions in the networks are theoretically described. Stationary non-linear viscosity and the dynamic mechanical moduli are calculated as functions of the shear rate, frequency and the chain disengagement rate. From the peak of the loss modulus, the lifetime τ_× of the junction is estimated, and from the high frequency plateau of the storage modulus, the number of elastically effective chains in the network is found. Transient phenomena such as stress relaxation and stress overshoot are also theoretically studied. Results are compared with the recent experimental reports on the rheological study of hydrophobically modified water-soluble polymers.

Chris H Greene - One of the best experts on this subject based on the ideXlab platform.

  • nonadiabatic Molecular Association in thermal gases driven by radio frequency pulses
    Physical Review Letters, 2019
    Co-Authors: P Giannakeas, Lev Khaykovich, Jan M Rost, Chris H Greene
    Abstract:

    : The Molecular Association process in a thermal gas of ^{85}Rb is investigated where the effects of the envelope of the radio-frequency field are taken into account. For experimentally relevant parameters our analysis shows that with increasing pulse length the corresponding Molecular conversion efficiency exhibits low-frequency interference fringes which are robust under thermal averaging over a wide range of temperatures. This dynamical interference phenomenon is attributed to Stuckelberg phase accumulation between the low-energy continuum states and the dressed Molecular state which exhibits a shift proportional to the envelope of the radio-frequency pulse intensity.