Segregation analysis of autosomal dominant polycystic kidney disease.

Abstract:

:The results of classical segregation analysis on 159 families with polycystic kidney disease (PKD) are presented. It had been previously estimated that about 95% of autosomal dominant PKD (ADPKD) families have PKD1, the gene localized to chromosome 16p. The main purpose of the study was to determine if PKD shows any segregation distortion and to obtain new estimates of the age-dependent penetrance. Penetrance at the early ages of onset has increased during the last decade, presumably because of improvements in renal imaging and consequent earlier age of diagnosis. In the current study, the mean age of diagnosis was estimated to be 20 years, with a standard deviation (SD) of 15.94. Under the best fitting model (autosomal dominant), over 70% penetrance was estimated by age 30 years, over 95% by 50 years, and 99% by 55 years. Thus, diagnosis of this disease at an early age is possible without total reliance on DNA typing. The segregation ratio defined through the transmission probability in our model was not significantly different from 0.50, but its confidence limits were broad: 0.36 to 0.64. Neither transmission probability nor penetrance was significantly influenced by gender. The mutation rate was estimated to be 6.9 x 10(-5), in accordance with the previously observed high mutation rate for PKD. However, the mutation rate in our study may be overestimated because it neglects low penetrance alleles and phenocopies.

journal_name

Genet Epidemiol

journal_title

Genetic epidemiology

authors

Dobin A,Kimberling WJ,Pettinger W,Bailey-Wilson JE,Shugart YY,Gabow P

doi

10.1002/gepi.1370100305

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

189-200

issue

3

eissn

0741-0395

issn

1098-2272

journal_volume

10

pub_type

杂志文章
  • Sequencing and imputation in GWAS: Cost-effective strategies to increase power and genomic coverage across diverse populations.

    abstract::A key aim for current genome-wide association studies (GWAS) is to interrogate the full spectrum of genetic variation underlying human traits, including rare variants, across populations. Deep whole-genome sequencing is the gold standard to fully capture genetic variation, but remains prohibitively expensive for large...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22326

    authors: Quick C,Anugu P,Musani S,Weiss ST,Burchard EG,White MJ,Keys KL,Cucca F,Sidore C,Boehnke M,Fuchsberger C

    更新日期:2020-09-01 00:00:00

  • POLARIS: Polygenic LD-adjusted risk score approach for set-based analysis of GWAS data.

    abstract::Polygenic risk scores (PRSs) are a method to summarize the additive trait variance captured by a set of SNPs, and can increase the power of set-based analyses by leveraging public genome-wide association study (GWAS) datasets. PRS aims to assess the genetic liability to some phenotype on the basis of polygenic risk fo...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22117

    authors: Baker E,Schmidt KM,Sims R,O'Donovan MC,Williams J,Holmans P,Escott-Price V,Consortium WTG

    更新日期:2018-06-01 00:00:00

  • Mantel statistics to correlate gene expression levels from microarrays with clinical covariates.

    abstract::Mantel statistics provide an additional step to standard approaches in the analysis of gene expression and covariate data, allow the calculation of standard statistics such as correlation, partial correlation, and regression coefficients, and, with permutation tests, provide P values for these statistics to relate the...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1115

    authors: Shannon WD,Watson MA,Perry A,Rich K

    更新日期:2002-06-01 00:00:00

  • Using case-control designs for genome-wide screening for associations between genetic markers and disease susceptibility loci.

    abstract::We used a case-control design to scan the genome for any associations between genetic markers and disease susceptibility loci using the first two replicates of the Mycenaean population from the GAW11 (Problem 2) data. Using a case-control approach, we constructed a series of 2-by-3 tables for each allele of every mark...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.13701707128

    authors: Yang Q,Khoury MJ,Atkinson M,Sun F,Cheng R,Flanders WD

    更新日期:1999-01-01 00:00:00

  • Tag SNPs chosen from HapMap perform well in several population isolates.

    abstract::Population isolates may be particularly useful for association studies of complex traits. This utility, however, largely depends on the transferability of tag SNPs chosen from reference samples, such as HapMap, to samples from such populations. Factors that characterize population isolates, such as widespread genetic ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20201

    authors: Service S,International Collaborative Group on Isolated Populations.,Sabatti C,Freimer N

    更新日期:2007-04-01 00:00:00

  • A general autosomal/X-linked model.

    abstract::This paper describes a general genetic model which encompasses both autosomal and X-linked inheritance as submodels. It allows one to test for X-linked inheritance of a trait by comparing the likelihood of X-linked inheritance to the likelihood of the general genetic model. The general model is formulated as two loci,...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370010105

    authors: Hasstedt SJ,Skolnick M

    更新日期:1984-01-01 00:00:00

  • Detecting interactions between gene, site, and environmental variables using GAP.

    abstract::Regressive models that incorporate measured variables and assumed genetic parameters were used to detect interactions between gene, research site, and environmental variables in GAW11 Problem 2. Replicates 1 to 5 were used in the analyses. Significant three-way gene x environment x site interactions were seen for all ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.13701707118

    authors: Shin J,Corey M

    更新日期:1999-01-01 00:00:00

  • Identifying SNPs predictive of phenotype using random forests.

    abstract::There has been a great interest and a few successes in the identification of complex disease susceptibility genes in recent years. Association studies, where a large number of single-nucleotide polymorphisms (SNPs) are typed in a sample of cases and controls to determine which genes are associated with a specific dise...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20041

    authors: Bureau A,Dupuis J,Falls K,Lunetta KL,Hayward B,Keith TP,Van Eerdewegh P

    更新日期:2005-02-01 00:00:00

  • Comparison of two linkage inference procedures for genes related to the P300 component of the event related potential.

    abstract::Our goal was to detect genes contributing to the P300 component of the event related potential (ERP). We found that all of the ERP traits were highly correlated. Most of them distinguished alcoholics from nonalcoholics. To have one summary variable for the ERP traits, we calculated the first principal component (PRIN1...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370170728

    authors: Goldin LR,Chase GA

    更新日期:1999-01-01 00:00:00

  • Mapping alcoholism genes using linkage/linkage disequilibrium analysis.

    abstract::Using a recently developed semiparametric method for combined linkage/linkage-disequilibrium analysis, we analyzed the Collaborative Study on the Genetics of Alcoholism data subset developed for Genetic Analysis Workshop 11 (GAW11). This semiparametric approach estimates recombination fractions for linkage, marker log...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370170708

    authors: Aragaki C,Quiaoit F,Hsu L,Zhao LP

    更新日期:1999-01-01 00:00:00

  • Comparison of variance components, ANOVA and regression of offspring on midparent (ROMP) methods for SNP markers.

    abstract::An extension of the traditional regression of offspring on midparent (ROMP) method was used to estimate the heritability of the trait, test for marker association, and estimate the heritability attributable to a marker locus. The fifty replicates of the Genetic Analysis Workshop (GAW) 12 simulated general population d...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.2001.21.s1.s794

    authors: Pugh EW,Papanicolaou GJ,Justice CM,Roy-Gagnon MH,Sorant AJ,Kingman A,Wilson AF

    更新日期:2001-01-01 00:00:00

  • Entropy-supported marker selection and Mantel statistics for haplotype sharing analysis.

    abstract::Haplotype sharing analysis is a well-established option for the investigation of the etiology of complex diseases. The statistical power of haplotype association methods depends strongly on how the information of unobserved haplotypes can be captured by multilocus genotypes. In this study we combine an entropy-based m...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20491

    authors: Schulz A,Fischer C,Chang-Claude J,Beckmann L

    更新日期:2010-05-01 00:00:00

  • Autoimmune thyroid disease in type I diabetic families.

    abstract::The prevalence rate for autoimmune thyroid disease (ATD) is about 30 times higher in the type I diabetic (IDDM) families that were ascertained for Genetic Analysis Workshop 5 (GAW5) than in the general population. Two approaches were used to study the clustering of ATD and IDDM in these families: 1) HLA haplotype shar...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370060126

    authors: Payami H,Joe S,Thomson G

    更新日期:1989-01-01 00:00:00

  • Conditional multipoint linkage analysis using affected sib pairs: an alternative approach.

    abstract::Recently, Liang et al. ([2001b] Genet. Epidemiol. 21:105-122) proposed a conditional approach to assess linkage evidence on the target region by incorporating linkage information from an unlinked (reference) region using allele shared IBD (identity-by-decent) from affected sib pairs. This is carried out by conditionin...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10305

    authors: Chiu YF,Liang KY

    更新日期:2004-02-01 00:00:00

  • A combination test for detection of gene-environment interaction in cohort studies.

    abstract::Identifying gene-environment (G-E) interactions can contribute to a better understanding of disease etiology, which may help researchers develop disease prevention strategies and interventions. One big criticism of studying G-E interaction is the lack of power due to sample size. Studies often restrict the interaction...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22043

    authors: Coombes B,Basu S,McGue M

    更新日期:2017-07-01 00:00:00

  • Modelling the major histocompatibility complex susceptibility to RA using the MASC method.

    abstract::To explain the association between HLA-DRB1 gene and rheumatoid arthritis (RA), two main hypotheses have been proposed. The first, the shared epitope hypothesis, assumes a direct role of DRB1 in RA susceptibility. The second hypothesis assumes a recessive disease susceptibility gene in linkage disequilibrium with DRB1...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1998)15:4<419::AID-GEPI7>3

    authors: Génin E,Babron MC,McDermott MF,Mulcahy B,Waldron-Lynch F,Adams C,Clegg DO,Ward RH,Shanahan F,Molloy MG,O'Gara F,Clerget-Darpoux F

    更新日期:1998-01-01 00:00:00

  • Bayesian variable and model selection methods for genetic association studies.

    abstract::Variable selection is growing in importance with the advent of high throughput genotyping methods requiring analysis of hundreds to thousands of single nucleotide polymorphisms (SNPs) and the increased interest in using these genetic studies to better understand common, complex diseases. Up to now, the standard approa...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20353

    authors: Fridley BL

    更新日期:2009-01-01 00:00:00

  • Power of the linkage test for a heterogeneous disorder due to two independent inherited causes: a simulation study.

    abstract::We have conducted a simulation study in small pedigrees to investigate the power to detect linkage and heterogeneity for a disorder due to either one of two independent disease loci. We have considered a highly polymorphic marker locus (PIC = 70%) linked to one disease locus and unlinked to the second. The power to de...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370070306

    authors: Martinez M,Goldin LR

    更新日期:1990-01-01 00:00:00

  • Accounting for population stratification in DNA methylation studies.

    abstract::DNA methylation is an important epigenetic mechanism that has been linked to complex diseases and is of great interest to researchers as a potential link between genome, environment, and disease. As the scale of DNA methylation association studies approaches that of genome-wide association studies, issues such as popu...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21789

    authors: Barfield RT,Almli LM,Kilaru V,Smith AK,Mercer KB,Duncan R,Klengel T,Mehta D,Binder EB,Epstein MP,Ressler KJ,Conneely KN

    更新日期:2014-04-01 00:00:00

  • Estimating the power of variance component linkage analysis in large pedigrees.

    abstract::Variance component linkage analysis is commonly used to map quantitative trait loci (QTLs) in general pedigrees. Large pedigrees are especially attractive for these studies because they provide greater power per genotyped individual than small pedigrees. We propose accurate and computationally efficient methods to cal...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20160

    authors: Chen WM,Abecasis GR

    更新日期:2006-09-01 00:00:00

  • Explorative two-locus linkage analysis suggests a multiplicative interaction between the 7q32 and 16p13 myoclonic seizures-related photosensitivity loci.

    abstract::In traits suspected to be governed by at least two loci, linkage analysis incorporating the joint action of both loci may improve the power to detect linkage, increase the precision of estimating locus positions and provide insight into the underlying etiological mechanism. Recently, we mapped two susceptibility loci ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20190

    authors: Pinto D,Kasteleijn-Nolst Trenité DG,Cordell HJ,Mattheisen M,Strauch K,Lindhout D,Koeleman BP

    更新日期:2007-01-01 00:00:00

  • Phenotypic effects of apolipoprotein structural variation on lipid profiles: II. Apolipoprotein A-IV and quantitative lipid measures in the healthy women study.

    abstract::Apolipoprotein A-IV (APO A-IV) is a major protein component of mesenteric lymph chylomicrons and very-low-density lipoproteins. It is found in plasma predominantly unassociated with major lipoprotein fractions and in high density lipoproteins. APO A-IV exhibits structural heterogeneity owing to two codominant alleles,...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.1370060404

    authors: Eichner JE,Kuller LH,Ferrell RE,Kamboh MI

    更新日期:1989-01-01 00:00:00

  • Multipoint linkage mapping using sibpairs: non-parametric estimation of trait effects with quantitative covariates.

    abstract::Multipoint linkage analysis using sibpair designs remains a common approach to help investigators to narrow chromosomal regions for traits (either qualitative or quantitative) of interest. Despite its popularity, the success of this approach depends heavily on how issues such as genetic heterogeneity, gene-gene, and g...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20036

    authors: Chiou JM,Liang KY,Chiu YF

    更新日期:2005-01-01 00:00:00

  • Effect of linkage disequilibrium between markers in linkage and association analyses.

    abstract::Contributions to Group 17 of the Genetic Analysis Workshop 15 considered dense markers in linkage disequilibrium (LD) in the context of either linkage or association analysis. Three contributions reported on methods for modeling LD or selecting a subset of markers in linkage equilibrium to perform linkage analysis. Wh...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.20291

    authors: Dupuis J,Albers K,Allen-Brady K,Cho K,Elston RC,Kappen HJ,Tang H,Thomas A,Thomson G,Tsung E,Yang Q,Zhang W,Zhao K,Zheng G,Ziegler JT

    更新日期:2007-01-01 00:00:00

  • Pedigree disequilibrium tests for multilocus haplotypes.

    abstract::Association tests of multilocus haplotypes are of interest both in linkage disequilibrium mapping and in candidate gene studies. For case-parent trios, I discuss the extension of existing multilocus methods to include ambiguous haplotypes in tests of models which distinguish between the cis and trans phase. A likeliho...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.10252

    authors: Dudbridge F

    更新日期:2003-09-01 00:00:00

  • Genetic prediction in the Genetic Analysis Workshop 18 sequencing data.

    abstract::High-throughput sequencing data can be used to predict phenotypes from genotypes, and this corresponds to establishing a prognostic model. In extended pedigrees the relatedness of subjects provides additional information so that genetic values, fixed or random genetic components, and heritability can be estimated. At ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.21826

    authors: Ziegler A,Bohossian N,Diego VP,Yao C

    更新日期:2014-09-01 00:00:00

  • Joint analysis of multiple phenotypes using a clustering linear combination method based on hierarchical clustering.

    abstract::Emerging evidence suggests that a genetic variant can affect multiple phenotypes, especially in complex human diseases. Therefore, joint analysis of multiple phenotypes may offer new insights into disease etiology. Recently, many statistical methods have been developed for joint analysis of multiple phenotypes, includ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22263

    authors: Li X,Zhang S,Sha Q

    更新日期:2020-01-01 00:00:00

  • Generalization of the extended transmission disequilibrium test to two unlinked disease loci.

    abstract::The extended transmission disequilibrium test (ETDT) of Sham and Curtis [1995] is a powerful test of the null hypothesis of no linkage between a multi-allelic marker locus and a disease susceptibility locus of unknown location in the presence of association between alleles at the two loci. We propose a generalization ...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.13701707108

    authors: Morris A,Whittaker J

    更新日期:1999-01-01 00:00:00

  • Sample size calculations for linkage analysis using extreme sib pairs based on segregation analysis with the quantitative phenotype body weight as an example.

    abstract::One approach to establish linkage is based on allele-sharing methods for sib pairs. Recently, the use of extreme sib pairs (ESP) has been proposed to increase power for mapping quantitative traits in humans. Several approaches have been discussed. In this study, we calculate sample sizes for the various ESP approaches...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2272(1998)15:6<577::AID-GEPI3>3

    authors: Ziegler A,Hebebrand J

    更新日期:1998-01-01 00:00:00

  • Bias in parameter estimates due to omitting gene-environment interaction terms in case-control studies.

    abstract::Genetic studies are continuing to generate volumes and variety of data that can be used to examine the genetic effects. Often the effect of a genetic variant varies by nongenetic measures, what is traditionally defined as gene-environment interaction (G×E). If the G×E term is neglected, estimates of the main effects c...

    journal_title:Genetic epidemiology

    pub_type: 杂志文章

    doi:10.1002/gepi.22154

    authors: Lobach I

    更新日期:2018-12-01 00:00:00