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Johannes Dietter

Publications and source records attributed to Johannes Dietter.

2 recordsLinked to original sources
PubMed2004

Efficient two-trait-locus linkage analysis through program optimization and parallelization: application to hypercholesterolemia.

We have optimized and parallelized the GENEHUNTER-TWOLOCUS program that allows to perform linkage analysis with two trait loci in the multimarker context. The optimization of the serial program, before parallelization, results in a speedup of a factor of more than 10. The parallelization affects the two-locus-score calculation, which is predominant in terms of computation time. We obtain perfect speedup, that is, the computation time decreases exactly by a factor of the number of processors. In addition, two-locus LOD and NPL scores are now calculated for varying genetic positions of both disease loci, not just one locus varied and the position of the other disease locus fixed, as before. This results in easily interpretable 3-D plots. We have reanalyzed a pedigree with hypercholesterolemia using our new version of GENEHUNTER-TWOLOCUS. Whereas originally, two individuals had to be discarded due to excessive computation-time demands, the entire 17-bit pedigree could now be analyzed as a whole. We obtain a two-trait-locus LOD score of 5.49 under a multiplicative model, compared to LOD scores of 3.08 and 2.87 under a heterogeneity and additive model, respectively. This further increases evidence for linkage to both 1p36.1-p35 and 13q22-q32 regions, and corroborates the hypothesis that the two genes act in a multiplicative way on LDL cholesterol level. Furthermore, we compare the computation times for two-trait-locus analysis needed by the programs GENEHUNTER-TWOLOCUS, TLINKAGE, and SUPERLINK. Altogether, our algorithmic improvements of GENEHUNTER-TWOLOCUS allow researchers to analyze complex diseases under realistic two-trait-locus models with pedigrees of reasonable size and using many markers.

Computer Simulation↗
PubMed2003

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 representing the pattern of longitudinal change of the provided phenotypes, especially systolic blood pressure and body weight. We performed a linear regression of body weight and systolic blood pressure on age and took the slopes as new phenotypes for quantitative trait linkage analysis using the SOLAR package. There was no evidence for heritability of systolic blood pressure change. Heritability was estimated as 0.15 for adult life "body weight change", measured as the regression slope, and "body weight gain" (including only individuals with a positive regression slope), and as 0.22 for body weight "change up to 50" (regression slope of weight on age up to an age of 50). With multipoint analysis, two regions on the long arm of chromosome 8 showed the highest LOD scores of 1.6 at 152 cM for "body weight change" and of >1.9 around location 102 cM for "body weight gain" and "change up to 50". The latter two LOD scores almost reach the threshold for suggestive linkage. We conclude that the chromosome 8 region may harbor a gene acting on long-term body weight regulation, thereby contributing to the development of the metabolic syndrome.

Adult↗