Cooperative disease management programs.

Cooperative disease management programs sponsored by pharmaceutical companies and managed care organizations or health care providers can offer significant benefits to patients. They can be structured so as to comply with applicable OIG, FDA, and IRS regulations. Such programs must be structured for the benefit of patients, and not to require the use of or otherwise directly promote the selection of the sponsoring pharmaceutical company's products.

Transmission/disequilibrium test analysis of total serum IgE levels in the Hutterite and Collaborative Study on the Genetics of Asthma data sets.

The Hutterite and Collaborative Study on the Genetics of Asthma data sets provided by Genetic Analysis Workshop 12 were analyzed using a regression-based transmission/disequilibrium test that assesses linkage between a marker locus and quantitative trait locus when allelic association is present, as proposed by George et al. [Am J Hum Genet 65:236-45, 1999]. Because the same marker set and analytical technique was used, the results from these data sets are amenable for comparison. Statistically significant results common to both data sets were found on chromosomes 1 and 3. A noteworthy result, significant at p < 10(-4), was detected on chromosome 18 in the Hutterites.

Comparison of three methods for obtaining principal components from family data in genetic analysis of complex disease.

Three multivariate techniques used to derive principal components (PCs) from family data were compared for their ability to model family data and power to detect linkage. Using the simulated data from Genetic Analysis Workshop 12, the five quantitative traits were first adjusted for age, sex, and environmental factors 1 and 2. Then, standard PCs, PCs obtained from between-family covariance, and PCs obtained from within-family genetic covariance were derived and subjected to multivariate sib pair linkage analysis. The standard PCs obtained from the overall correlation matrix allowed identification of key features of the true genetic model more readily than did the other methods. For detection of linkage, standard PCs and PCs obtained from the between-family genetic covariance performed similarly in terms of both power and type 1 error, and both methods performed better than the PCs obtained from within-family genetic covariance.

Genome scan of human systemic lupus erythematosus by regression modeling: evidence of linkage and epistasis at 4p16-15.2.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving at least hormonal, environmental, and genetic factors. Familial aggregation, a 2%-3% sibling recurrence rate, monozygotic twin concordance >20%, association with several candidate genes, as well as the results of five genome scans support a genetic component. We present here the results of a genome scan of 126 pedigrees multiplex for SLE, including 469 sibling pairs (affected and unaffected) and 175 affected relative pairs. Using the revised multipoint Haseman-Elston regression technique for concordant and discordant sibling pairs and a conditional logistic regression technique for affected relative pairs, we identify a novel linkage to chromosome 4p16-15.2 (P=.0003 and LOD=3.84) and present evidence of an epistatic interaction between chromosome 4p16-15.2 and chromosome 5p15 in our European American families. We confirm the evidence of linkage to chromosome 4p16-15.2 in European American families using data from an independent pedigree collection. In addition, our data support the published results of three independent studies for nine purportedly linked regions and agree with the previously published results from a subset of these data for three regions. In summary, results from two new analytical techniques establish and confirm linkage with SLE at 4p16-15.2, indicate epistasis between 4p16-15.2 and 5p15, and confirm other linkage effects with SLE that have been reported elsewhere.