Volume 4 Supplement 1
Genetic Analysis Workshop 13: Analysis of Longitudinal Family Data for Complex Diseases and Related Risk Factors
Proceedings
Edited by Laura Almasy, Christopher I Amos, Joan E Bailey-Wilson, Rita M Cantor, Cashell E Jaquish, Maria Martinez, Rosalind J Neuman, Jane M Olson, Lyle J Palmer, Stephen S Rich, M Anne Spence, Jean W MacCluer
Genetic Analysis Workshop 13: Analysis of Longitudinal Family Data for Complex Diseases and Related Risk Factors. Go to conference site.
New Orleans, LA, USANovember 11-14, 2002
Page 1 of 3
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Citation: BMC Genetics 2003 4(Suppl 1):S1
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Description of the Framingham Heart Study data for Genetic Analysis Workshop 13
Citation: BMC Genetics 2003 4(Suppl 1):S2 -
Genetic Analysis Workshop 13: Simulated longitudinal data on families for a system of oligogenic traits
The Genetic Analysis Workshop 13 simulated data aimed to mimic the major features of the real Framingham Heart Study data that formed Problem 1, but under a known inheritance model and with 100 replicates, so ...
Citation: BMC Genetics 2003 4(Suppl 1):S3 -
Variance components linkage analysis for adjusted systolic blood pressure in the Framingham Heart Study
We performed variance components linkage analysis in nuclear families from the Framingham Heart Study on nine phenotypes derived from systolic blood pressure (SBP). The phenotypes were the maximum and mean SBP...
Citation: BMC Genetics 2003 4(Suppl 1):S4 -
Use of a random coefficient regression (RCR) model to estimate growth parameters
We used a random coefficient regression (RCR) model to estimate growth parameters for the time series of observed serum glucose levels in the Replicate 1 of the Genetic Analysis Workshop 13 simulated data. For...
Citation: BMC Genetics 2003 4(Suppl 1):S5 -
Linkage analysis of a derived glucose phenotype in the Genetic Analysis Workshop 13 simulated data using a variety of Haseman-Elston based regression methods
Citation: BMC Genetics 2003 4(Suppl 1):S6 -
Quantitative trait linkage analysis of longitudinal change in body weight
One of the great strengths of the Framingham Heart Study data, provided for the Genetic Analysis Workshop 13, is the long-term survey of phenotypic data. We used this unique data to create new phenotypes repre...
Citation: BMC Genetics 2003 4(Suppl 1):S7 -
An autosome-wide search using longitudinal data for loci linked to type 2 diabetes progression
A genome-wide screen was conducted for type 2 diabetes progression genes using measures of elevated fasting glucose levels as quantitative traits from the offspring enrolled in the Framingham Heart Study. We a...
Citation: BMC Genetics 2003 4(Suppl 1):S8 -
Detecting susceptibility genes in case-control studies using set association
Complex diseases are generally caused by intricate interactions of multiple genes and environmental factors. Most available linkage and association methods are developed to identify individual susceptibility g...
Citation: BMC Genetics 2003 4(Suppl 1):S9 -
Using simultaneous equation modeling for defining complex phenotypes
Interactions between multiple biological phenotypes are difficult to model. Simultaneous equation modelling (SEM), as used in econometric modelling, may prove an effective tool for this problem. Generalized li...
Citation: BMC Genetics 2003 4(Suppl 1):S10 -
Are there mappable genes for family resemblance for the magnitude of intra-individual variation in systolic blood pressure?
The genetic regulation of variation in intra-individual fluctuations in systolic blood pressure over time is poorly understood. Analysis of the magnitude of the average fluctuation of a person's systolic blood...
Citation: BMC Genetics 2003 4(Suppl 1):S11 -
Genome-wide linkage analysis of longitudinal phenotypes using σ2A random effects (SSARs) fitted by Gibbs sampling
The study of change in intermediate phenotypes over time is important in genetics. In this paper we explore a new approach to phenotype definition in the genetic analysis of longitudinal phenotypes. We utilize...
Citation: BMC Genetics 2003 4(Suppl 1):S12 -
Genome-wide linkage analysis of systolic blood pressure: a comparison of two approaches to phenotype definition
Problem 1 of the Genetic Analysis Workshop 13(GAW13) contains longitudinal data of cardiovascular measurements from 330 pedigrees. The longitudinal data complicates the phenotype definition because multiple me...
Citation: BMC Genetics 2003 4(Suppl 1):S13 -
The genetics of cross-sectional and longitudinal body mass index
There has been a lack of consistency in detecting chromosomal loci that are linked to obesity-related traits. This may be due, in part, to the phenotype definition. Many studies use a one-time, single measurem...
Citation: BMC Genetics 2003 4(Suppl 1):S14 -
Empirically derived phenotypic subgroups – qualitative and quantitative trait analyses
The Framingham Heart Study has contributed a great deal to advances in medicine. Most of the phenotypes investigated have been univariate traits (quantitative or qualitative). The aims of this study are to der...
Citation: BMC Genetics 2003 4(Suppl 1):S15 -
Power of maximum HLOD tests to detect linkage to obesity genes
We investigate the power of heterogeneity LOD test to detect linkage when a trait is determined by several major genes using Genetic Analysis Workshop 13 simulated data. We consider three traits, two of which ...
Citation: BMC Genetics 2003 4(Suppl 1):S16 -
Comparison of longitudinal variance components and regression-based approaches for linkage detection on chromosome 17 for systolic blood pressure
We compare two methods to detect genetic linkage by using serial observations of systolic blood pressure in pedigree data from the Framingham Heart Study focusing on chromosome 17. The first method is a varian...
Citation: BMC Genetics 2003 4(Suppl 1):S17 -
Analysis of gene × environment interactions in sibships using mixed models
Gene × environment models are widely used to assess genetic and environmental risks and their association with a phenotype of interest for many complex diseases. Mixed generalized linear models were used to as...
Citation: BMC Genetics 2003 4(Suppl 1):S18 -
Multilevel modeling for the analysis of longitudinal blood pressure data in the Framingham Heart Study pedigrees
The data arising from a longitudinal familial study have a complex correlation structure that cannot be modeled using classical methods for the analysis of familial data at a single time point.
Citation: BMC Genetics 2003 4(Suppl 1):S19 -
Comparison of the linkage results of two phenotypic constructs from longitudinal data in the Framingham Heart Study: analyses on data measured at three time points and on the average of three measurements
Family studies are often conducted in a cross-sectional manner without long-term follow-up data. The relative contribution of a gene to a specific trait could change over the lifetime. The Framingham Heart Stu...
Citation: BMC Genetics 2003 4(Suppl 1):S20 -
Segregation and linkage analysis for longitudinal measurements of a quantitative trait
We present a method for using slopes and intercepts from a linear regression of a quantitative trait as outcomes in segregation and linkage analyses. We apply the method to the analysis of longitudinal systoli...
Citation: BMC Genetics 2003 4(Suppl 1):S21 -
Longitudinal variance-components analysis of the Framingham Heart Study data
The Framingham Heart Study offspring cohort, a complex data set with irregularly spaced longitudinal phenotype data, was made available as part of Genetic Analysis Workshop 13. To allow an analysis of all of t...
Citation: BMC Genetics 2003 4(Suppl 1):S22 -
Comparison of Haseman-Elston regression analyses using single, summary, and longitudinal measures of systolic blood pressure
To compare different strategies for linkage analyses of longitudinal quantitative trait measures, we applied the "revisited" Haseman-Elston (RHE) regression model (the cross product of centered sib-pair trait ...
Citation: BMC Genetics 2003 4(Suppl 1):S23 -
Genetic linkage analysis of longitudinal hypertension phenotypes using three summary measures
Longitudinal data often have multiple (repeated) measures recorded along a time trajectory. For example, the two cohorts from the Framingham Heart Study (GAW13 Problem 1) contain 21 and 5 repeated measures for...
Citation: BMC Genetics 2003 4(Suppl 1):S24 -
Longitudinal variance components models for systolic blood pressure, fitted using Gibbs sampling
This paper describes an analysis of systolic blood pressure (SBP) in the Genetic Analysis Workshop 13 (GAW13) simulated data. The main aim was to assess evidence for both general and specific genetic effects o...
Citation: BMC Genetics 2003 4(Suppl 1):S25 -
Linkage analysis of cross-sectional and longitudinally derived phenotypic measures to identify loci influencing blood pressure
The design of appropriate strategies to analyze and interpret linkage results for complex human diseases constitutes a challenge. Parameters such as power, definition of phenotype, and replicability have to be...
Citation: BMC Genetics 2003 4(Suppl 1):S26 -
Linkage analysis of longitudinal data
We propose a statistical model for linkage analysis of the longitudinal data. The proposed model is a mixed model based on the new Haseman and Elston model and allows several random effects. Specifically, the ...
Citation: BMC Genetics 2003 4(Suppl 1):S27 -
Power of linkage analysis using traits generated from simulated longitudinal data of the Framingham Heart Study
The Framingham Heart Study is a very successful longitudinal research for cardiovascular diseases. The completion of a 10-cM genome scan in Framingham families provided an opportunity to evaluate linkage using...
Citation: BMC Genetics 2003 4(Suppl 1):S28 -
Genetic analyses of longitudinal phenotype data: a comparison of univariate methods and a multivariate approach
We explored three approaches to heritability and linkage analyses of longitudinal total cholesterol levels (CHOL) in the Genetic Analysis Workshop 13 simulated data without knowing the answers. The first two w...
Citation: BMC Genetics 2003 4(Suppl 1):S29 -
Consistency of linkage results across exams and methods in the Framingham Heart Study
The repeated measures in the Framingham Heart Study in the Genetic Analysis Workshop 13 data set allow us to test for consistency of linkage results within a study across time. We compared regression-based lin...
Citation: BMC Genetics 2003 4(Suppl 1):S30 -
Age-Stratified QTL Genome Scan Analyses for Anthropometric Measures
With the availability of longitudinal data, age-specific (stratified) or age-adjusted genetic analyses have the potential to localize different putative trait influencing loci. If age does not influence the lo...
Citation: BMC Genetics 2003 4(Suppl 1):S31 -
Age-stratified heritability estimation in the Framingham Heart Study families
The Framingham Heart Study provides a unique source of longitudinal family data related to CVD risk factors. Age-stratified heritability estimates were obtained over three age groups (31–49 years, 50–60 years,...
Citation: BMC Genetics 2003 4(Suppl 1):S32 -
Sibling recurrence risk ratio analysis of the metabolic syndrome and its components over time
The purpose of this study was to estimate both cross-sectional sibling recurrence risk ratio (λ s ) and lifetime λ s for the metabolic s...
Citation: BMC Genetics 2003 4(Suppl 1):S33 -
Strategy and model building in the fourth dimension: a null model for genotype × age interaction as a Gaussian stationary stochastic process
Using univariate and multivariate variance components linkage analysis methods, we studied possible genotype × age interaction in cardiovascular phenotypes related to the aging process from the Framingham Hear...
Citation: BMC Genetics 2003 4(Suppl 1):S34 -
Genome-wide linkage analysis using cross-sectional and longitudinal traits for body mass index in a subsample of the Framingham Heart Study
To evaluate linkage evidence for body mass index (BMI) using both cross-sectional and longitudinal data, we performed genome-wide multipoint linkage analyses on subjects who had complete data at four selected ...
Citation: BMC Genetics 2003 4(Suppl 1):S35 -
Comparison of year-of-exam- and age-matched estimates of heritability in the Framingham Heart Study data
Several different approaches can be used to examine generational and temporal trends in family studies. The measurement of offspring and parents can be made over a short period of time with parents and offspri...
Citation: BMC Genetics 2003 4(Suppl 1):S36 -
Lack of reproducibility of linkage results in serially measured blood pressure data
Using the longitudinal Framingham Heart Study data on blood pressure, we analyzed the reproducibility of linkage measures from serial cross-sectional surveys of a defined population by performing genome-wide m...
Citation: BMC Genetics 2003 4(Suppl 1):S37 -
Stability of exploratory multivariate data modeling in longitudinal data
Exploratory data-driven multivariate analysis provides a means of investigating underlying structure in complex data. To explore the stability of multivariate data modeling, we have applied a common method of ...
Citation: BMC Genetics 2003 4(Suppl 1):S38 -
Bootstrap calibration of TRANSMIT for informative missingness of parental genotype data
Informative missingness of parental genotype data occurs when the genotype of a parent influences the probability of the parent's genotype data being observed. Informative missingness can occur in a number of ...
Citation: BMC Genetics 2003 4(Suppl 1):S39 -
An examination of the genotyping error detection function of SIMWALK2
This investigation was undertaken to assess the sensitivity and specificity of the genotyping error detection function of the computer program SIMWALK2. We chose to examine chromosome 22, which had 7 microsate...
Citation: BMC Genetics 2003 4(Suppl 1):S40 -
Pedigree and genotype errors in the Framingham Heart Study
The pedigree and genotype data from the Framingham Heart Study were examined for errors. Errors in 21 of 329 pedigrees were detected with the program PREST, and of these the errors in 16 pedigrees were resolve...
Citation: BMC Genetics 2003 4(Suppl 1):S41 -
Imputation methods for missing data for polygenic models
Methods to handle missing data have been an area of statistical research for many years. Little has been done within the context of pedigree analysis. In this paper we present two methods for imputing missing ...
Citation: BMC Genetics 2003 4(Suppl 1):S42 -
Multiple imputation methods for longitudinal blood pressure measurements from the Framingham Heart Study
Missing data are a great concern in longitudinal studies, because few subjects will have complete data and missingness could be an indicator of an adverse outcome. Analyses that exclude potentially informative...
Citation: BMC Genetics 2003 4(Suppl 1):S43 -
Comparison of missing data approaches in linkage analysis
Observational cohort studies have been little used in linkage analyses due to their general lack of large, disease-specific pedigrees. Nevertheless, the longitudinal nature of such studies makes them potential...
Citation: BMC Genetics 2003 4(Suppl 1):S44 -
Interaction of gender and body mass index (BMI) reveals evidence of linkage for hypertension in the Framingham Heart Study
Genetic heterogeneity and complex biologic mechanisms of blood pressure regulation pose significant challenges to the identification of susceptibility loci influencing hypertension. Previous linkage studies ha...
Citation: BMC Genetics 2003 4(Suppl 1):S45 -
Comparison of significance level at the true location using two linkage approaches: LODPAL and GENEFINDER
We compare two new software packages for linkage analysis, LODPAL and GENEFINDER. Both allow for covariate adjustment. Replicates 1 to 3 of Genetic Analysis Workshop 13 simulated data sets were used for the an...
Citation: BMC Genetics 2003 4(Suppl 1):S46 -
Genome-wide scan on plasma triglyceride and high density lipoprotein cholesterol levels, accounting for the effects of correlated quantitative phenotypes
Plasma triglyceride and high density lipoprotein cholesterol levels are inversely correlated and both are genetically related. Two correlated traits may be influenced both by shared and unshared genes. The pow...
Citation: BMC Genetics 2003 4(Suppl 1):S47 -
Transmission ratio distortion in families from the Framingham Heart Study
One implicit assumption in most linkage analysis is that live-born siblings unselected for a phenotype do not share alleles greater than the Mendelian expectation at any particular locus. However, since most f...
Citation: BMC Genetics 2003 4(Suppl 1):S48 -
Susceptibility scoring in family-based association testing
Family-based association testing is an important part of genetic epidemiology. Tests are available to include multiple siblings, unaffected offspring, and to adjust for environmental covariates. We explore a s...
Citation: BMC Genetics 2003 4(Suppl 1):S49 -
Adjusting for covariates on a slippery slope: linkage analysis of change over time
We analyzed the Genetic Analysis Workshop 13 (GAW13) simulated data to contrast and compare different methods for the genetic linkage analysis of hypertension and change in blood pressure over time. We also ex...
Citation: BMC Genetics 2003 4(Suppl 1):S50
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