Abstract
BackgroundOften, multiple measures of a trait are available in a genetic linkage analysis. We compare Monte Carlo Markov chain analysis of two very different measures of hypertension in the simulated Genetic Analysis Workshop 13 data to examine how choice of measure affects the results. The measures selected were age-of-onset of hypertension and systolic blood pressure at first visit.ResultsIn combined segregation and linkage analysis of the complete pedigrees using the first replicate of the simulated data with missing values, we found that the age-of-onset analysis was better at identifying "slope" genes, while the systolic blood pressure analysis was better at identifying "baseline" genes.ConclusionAnalysis of different trait measures may identify different trait-related genes. When linkage analysis is conducted on multiple trait measures, a linkage signal found for only one measure can represent a true trait locus.
Highlights
Often, multiple measures of a trait are available in a genetic linkage analysis
In studies such as the Framingham Heart Study (e.g. [1]) or the Collaborative Study on the Genetics of Alcoholism (COGA) [2], a number of different values related to a disease are measured, and the first step in the analysis may be choosing one measure
The simulated data in Genetic Analysis Workshop 13 (GAW13), for example, offered many measures related to hypertension
Summary
Multiple measures of a trait are available in a genetic linkage analysis. We compare Monte Carlo Markov chain analysis of two very different measures of hypertension in the simulated Genetic Analysis Workshop 13 data to examine how choice of measure affects the results. We compared two different simulated measures of hypertension in analyses with Monte Carlo Markov chain (MCMC) oligogenic combined segregation and linkage analysis, as implemented in the program Loki [4]. These methods use linkage data on extended pedigrees and estimate the number, location, and effects of loci that contribute to a quantitative trait. We chose two measures of a type that might be collected in a retrospective study: age-ofonset of hypertension (AOH) and systolic blood pressure at the first visit (SBP) We made these choices with knowledge of the generating model. We wanted to determine whether these different measures would localize different trait loci
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