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

The effect of linkage disequilibrium on linkage analysis of incomplete pedigrees

Dense SNP maps can be highly informative for linkage studies. But when parental genotypes are missing, multipoint linkage scores can be inflated in regions with substantial marker-marker linkage disequilibrium (LD). Such regions were observed in the Affymetrix SNP genotypes for the Genetic Analysis Workshop 14 (GAW14) Collaborative Study on the Genetics of Alcoholism (COGA) dataset, providing an opportunity to test a novel simulation strategy for studying this problem. First, an inheritance vector (with or without linkage present) is simulated for each replicate, i.e., locations of recombinations and transmission of parental chromosomes are determined for each meiosis. Then, two sets of founder haplotypes are superimposed onto the inheritance vector: one set that is inferred from the actual data and which contains the pattern of LD; and one set created by randomly selecting parental alleles based on the known allele frequencies, with no correlation (LD) between markers. Applying this strategy to a map of 176 SNPs (66 Mb of chromosome 7) for 100 replicates of 116 sibling pairs, significant inflation of multipoint linkage scores was observed in regions of high LD when parental genotypes were set to missing, with no linkage present. Similar inflation was observed in analyses of the COGA data for these affected sib pairs with parental genotypes set to missing, but not after reducing the marker map until r(2 )between any pair of markers was ≤ 0.05. Additional simulation studies of affected sib pairs assuming uniform LD throughout a marker map demonstrated inflation of significance levels at r(2 )values greater than 0.05. When genotypes are available only from two affected siblings in many families in a sample, trimming SNP maps to limit r(2 )to 0–0.05 for all marker pairs will prevent inflation of linkage scores without sacrificing substantial linkage information. Simulation studies on the observed pedigree structures and map can also be used to determine the effect of LD on a particular study

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

Recent trends in the size and the distribution of inherited wealth in the UK

In this paper we use HMRC estate statistics and micro-data from four UK household surveys to examine changes in the size, the composition and the distribution of inherited wealth in the UK over the period 1985-2010. Our findings indicate that the period under examination is characterised by a substantial increase in the flow of inheritance. This increase, which was particularly marked in the early 2000s, was mainly driven by the rise in house prices and to a lesser extent by the increase in the proportion of inheritances which included housing assets. The distribution of inheritance amongst recipients became more unequal over this period. However, the inequality-increasing effect from the greater dispersion in the distribution of inheritance was counterbalanced by the increase in the percentage of the population who received an inheritance, resulting in a small decrease in the inequality of inheritance for the population overall. Analysis of the distribution of inheritance by socio-economic status suggests a positive association between inheritance and socio-economic status with some suggestive evidence that this association might have strengthened over time. Overall, however, the value of inheritance for most people is rather small and the differences across groups rather moderate

What is the pathogenic CAG expansion length in Huntington’s disease?

Huntington’s disease (HD) (OMIM 143100) is caused by an expanded CAG repeat tract in the HTT gene. The inherited CAG length is known to expand further in somatic and germline cells in HD subjects. Age at onset of the disease is inversely correlated with the inherited CAG length, but is further modulated by a series of genetic modifiers which are most likely to act on the CAG repeat in HTT that permit it to further expand. Longer repeats are more prone to expansions, and this expansion is age dependent and tissue-specific. Given that the inherited tract expands through life and most subjects develop disease in mid-life, this implies that in cells that degenerate, the CAG length is likely to be longer than the inherited length. These findings suggest two thresholds – the inherited CAG length which permits further expansion, and the intracellular pathogenic threshold, above which cells become dysfunctional and die. This two-step mechanism has been previously proposed and modelled mathematically to give an intracellular pathogenic threshold at a tract length of 115 CAG (95% confidence intervals 70-165 CAG). Empirically, the intracellular pathogenic threshold is difficult to determine. Clues from studies of people and models of HD, and from other diseases caused by expanded repeat tracts, place this threshold between 60-100 CAG, most likely towards the upper part of that range. We assess this evidence and discuss how the intracellular pathogenic threshold in manifest disease might be better determined. Knowing the cellular pathogenic threshold would be informative for both understanding the mechanism in HD and deploying treatments

Familial phenotype differences in PKD1111See Editorial, p. 344.

Familial phenotype differences in PKD1.BackgroundMutations within the PKD1 gene are responsible for the most common and most severe form of autosomal dominant polycystic kidney disease (ADPKD). Although it is known that there is a wide range of disease severity within PKD1 families, it is uncertain whether differences in clinical severity also occur among PKD1 families.MethodsTen large South Wales ADPKD families with at least 12 affected members were included in the study. From affected members, clinical information was obtained, including survival data and the presence of ADPKD-associated complications. Family members who were at risk of having inherited ADPKD but were proven to be non-affected were included as controls. Linkage and haplotype analysis were performed with highly polymorphic microsatellite markers closely linked to the PKD1 gene. Survival data were analyzed by the Kaplan–Meier method and the log rank test. Logistic regression analysis was used to test for differences in complication rates between families.ResultsHaplotype analysis revealed that each family had PKD1-linked disease with a unique disease-associated haplotype. Interfamily differences were observed in overall survival (P = 0.0004), renal survival (P = 0.0001), hypertension prevalence (P = 0.013), and hernia (P = 0.048). Individuals with hypertension had significantly worse overall (P = 0.0085) and renal (P = 0.03) survival compared with those without hypertension. No statistically significant differences in the prevalence of hypertension and hernia were observed among controls.ConclusionWe conclude that phenotype differences exist between PKD1 families, which, on the basis of having unique disease-associated haplotypes, are likely to be associated with a heterogeneous range of underlying PKD1 mutations

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