Conditional variances in UK regional house prices

The returns of house price indices for the 13 UK regions are modelled using time series processes, including conditional variances. The first conclusion is that the UK follows the USA, with some regions displaying time-varying variances and others with constant variances. Secondly, there is limited evidence of an asymmetric component in six of the seven regions displaying autoregressive conditional heteroskedasticity. Thirdly, the results suggest that there are three distinct housing markets in the UK, based on common structures within their mean and variance processes, and that South West England is the region driving the other time-varying variances. Variances conditionnelles dans les prix regionaux de l'immobilier au Royaume-Uni Resume Les resultats de l'indice des prix de l'immobilier pour les 13 regions du Royaume-Uni sont modelises ici au moyen de procedes de series chronologiques, y compris des variances conditionnelles. La premiere conclusion est que le Royaume-Uni suit les Etats-Unis, certaines regions presentant des variances temporelles, d'autres des variances constantes. Deuxiemement, on releve peu de traces d'un composant asymetrique dans six des sept regions presentant une heteroscedasticite conditionnelle autoregressive. Troisiemement, les resultats indiquent qu'il y aurait trois marches de l'immobilier distincts au Royaume-Uni, sur la base de structures communes dans le cadre de leurs procedes moyens et de variance, et que le sud-ouest de l'Angleterre est la region qui dynamise les autres variances temporelles. Varianzas condicionales en los precios regionales de la vivienda en el Reino Unido Extracto Las cifras de los indices de precios de la vivienda en 13 regiones del Reino Unido se modelan utilizando procesos de series temporales, incluyendo varianzas condicionales. La primera conclusion es que el Reino Unido sigue a los EE UU, con varias regiones que muestran varianzas fluctuantes con el tiempo y otras con varianzas constantes. En segundo lugar, existe evidencia limitada de un componente asimetrico en seis de las siete regiones que muestran una heteroesquedacidad condicional autorregresiva. En tercer lugar, los resultados sugieren que existen tres mercados distintivos de la vivienda en el Reino Unido, basados en estructuras comunes dentro de sus procesos de media y varianza, y que el sudoeste de Inglaterra es la region que dirige las otras varianzas fluctuantes con el tiemp

Convergent genetic and expression data implicate immunity in Alzheimer's disease

© 2015, Elsevier Inc. All rights reserved. Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10-12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10-11), cholesterol transport (P = 2.96 × 10-9), and proteasome-ubiquitin activity (P = 1.34 × 10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P =.002-.05). Conclusions: The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.Medical Research Council, Alzheimer’s Research UK, and theWelsh Assembly Government. ADGC and CHARGE were supported by the National Institutes of Health, National Institute on Aging (NIH-NIA). CHARGE was also supported by Erasmus Medical Center and Erasmus University. IGAP was funded by the French National Foundation on Alzheimer’s Disease and Related Disorders, the Centre National de Genotypage and the Institut Pasteur de Lille, Inserm, FRC (Fondation pour la Recherche sur le Cerveau), and Rotary. This work has been developed and supported by the LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease).Peer Reviewe

Covariate linkage analysis of GAW14 simulated data incorporating subclinical phenotype, sex, population, parent-of-origin, and interaction

BACKGROUND: We evaluate a method for the incorporation of covariates into linkage analysis using the Genetic Analysis Workshop 14 simulated data. Focusing on a randomly chosen replicate (42) we investigated the effect of the 12 subclinical phenotypes, sex, population, and parent-of-origin on the linkage signal from a model-free linkage analysis of Kofendrerd Personality Disorder. RESULTS: We detected a linkage peak on chromosome 1, at about 175 cM, which varied depending upon individuals' status for subclinical phenotype b. A linkage peak on chromosome 3 (310 cM) was found not to depend upon subclinical phenotype status. Further peaks were found on chromosomes 5 (12 cM), 9 (4 cM), and 10 (95 cM), depending on the status of subclinical phenotypes a, k, and c/d/g, respectively. CONCLUSION: Retrospective comparison of our results with the simulation model showed correct identification of disease loci D1-5 on chromosomes 1, 3, 5, 9 and 10, respectively

Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis

Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates

Combining linkage data sets for meta-analysis and mega-analysis: the GAW15 rheumatoid arthritis data set

We have used the genome-wide marker genotypes from Genetic Analysis Workshop 15 Problem 2 to explore joint evidence for genetic linkage to rheumatoid arthritis across several samples. The data consisted of four high-density genome scans on samples selected for rheumatoid arthritis. We cleaned the data, removed intermarker linkage disequilibrium, and assembled the samples onto a common genetic map using genome sequence positions as a reference for map interpolation. The individual studies were combined first at the genotype level (mega-analysis) prior to a multipoint linkage analysis on the combined sample, and second using the genome scan meta-analysis method after linkage analysis of each sample. The two approaches were compared, and give strong support to the HLA locus on chromosome 6 as a susceptibility locus. Other regions of interest include loci on chromosomes 11, 2, and 12

Genetic modifiers of Mendelian disease: Huntington's disease and the trinucleotide repeat disorders

In the decades since the genes and mutations associated with the commoner Mendelian disorders were first discovered, technological advances in genetic analysis have made finding genomic variation a much less onerous task. Recently, the global efforts to collect subjects with Mendelian disorders, to better define the disorders and to empower appropriate clinical trials, along with improved genetic technologies, have allowed the identification of genetic variation that does not cause disease, but substantially modifies disease presentation. The advantage of this is it identifies biological pathways and molecules, that, if modified in people, might alter disease presentation. In Huntington’s disease (HD), caused by an expanded CAG repeat tract in HTT, genetic variation has been uncovered that is associated with change in the onset or progression of disease. Some of this variation lies in genes that are part of the DNA damage response, previously suggested to be important in modulating expansion of the repeat tract in germline and somatic cells. The genetic evidence implicates a DNA damage response-related pathway in modulating the pathogenicity of the repeat tracts in HD, and possibly, in other trinucleotide repeat disorders. These findings offer new targets for drug development in these currently intractable disorders

A new perspective on the ripple effect in the UK housing market: Comovement, cyclical subsamples and alternative indices

An alternative perspective is provided on the existence of a ripple effect in the UK housing market. In contrast to previous studies, the analysis involves consideration of information on the changes in house prices to which the hypothesis of house price diffusion posited by the ripple effect relates, rather than their levels. In an examination of changes in house prices in London relative to other regions of the UK, directional forecasting methods are employed to establish the extent of the relationship between geographical proximity and comovement across the three month window provided by quarterly data. Consequently, the analysis provides a direct examination of the ripple effect which refers to changes in prices rather than the convergence of levels which has become a feature of the empirical literature. The literature is extended further by both the application of dating techniques to perform the analysis across cycles and phases of cycles (recovery and recessionary periods) in the UK housing market, and the use of data from two alternative house price index providers. Striking results in support of the presence of a ripple effect are noted, particularly for the less commonly considered Halifax price index where the most significant results for comovement with London are exhibited by its contiguous regions. In addition, the cyclical subsamples considered indicate comovement to be greater during upturns, rather than downturns in the market. This is consistent with previous research showing London to correct – that is, exhibit differing behaviour to other regions – during downturns

Parameter Estimation and Quantitative Parametric Linkage Analysis with GENEHUNTER-QMOD

Objective: We present a parametric method for linkage analysis of quantitative phenotypes. The method provides a test for linkage as well as an estimate of different phenotype parameters. We have implemented our new method in the program GENEHUNTER-QMOD and evaluated its properties by performing simulations. Methods: The phenotype is modeled as a normally distributed variable, with a separate distribution for each genotype. Parameter estimates are obtained by maximizing the LOD score over the normal distribution parameters with a gradient-based optimization called PGRAD method. Results: The PGRAD method has lower power to detect linkage than the variance components analysis (VCA) in case of a normal distribution and small pedigrees. However, it outperforms the VCA and Haseman-Elston regression for extended pedigrees, nonrandomly ascertained data and non-normally distributed phenotypes. Here, the higher power even goes along with conservativeness, while the VCA has an inflated type I error. Parameter estimation tends to underestimate residual variances but performs better for expectation values of the phenotype distributions. Conclusion: With GENEHUNTER-QMOD, a powerful new tool is provided to explicitly model quantitative phenotypes in the context of linkage analysis. It is freely available at http://www.helmholtz-muenchen.de/genepi/downloads. Copyright (C) 2012 S. Karger AG, Base

Affordability targets: Implications for Housing Supply

This report presents the results of an econometric modelling project, concerned with regional housing affordability, conducted for the ODPM between November 2004 and April 2005. The key outputs of the project are not just this report, but the model itself, the details of which are set out in the accompanying Technical Appendix, available via the ODPM website: www.odpm.gov.uk/housing. The team for the project was large, including fifteen individuals from nine organisations. The project was directed from the University of Reading. In addition to the team, the work was improved by help from an advisory group and a user group, consisting of members drawn from both central government and from the wider academic and policy communities