Heritability of the severity of diabetic retinopathy: the FIND-Eye study.

Purpose: Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families.

Density-based clustering in haplotype analysis for association mapping.

Clustering of related haplotypes in haplotype-based association mapping has the potential to improve power by reducing the degrees of freedom without sacrificing important information about the underlying genetic structure. We have modified a generalized linear model approach for association analysis by incorporating a density-based clustering algorithm to reduce the number of coefficients in the model. Using the GAW 15 Problem 3 simulated data, we show that our novel method can substantially enhance power to detect association with the binary rheumatoid arthritis (RA) phenotype at the HLA-DRB1 locus on chromosome 6.

Genome-wide scans for diabetic nephropathy and albuminuria in multiethnic populations: the family investigation of nephropathy and diabetes (FIND).

The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase genetic analyses in 1,227 participants from 378 pedigrees of European-American, African-American, Mexican-American, and American Indian descent recruited from eight centers.

Linkage analysis of alcoholism-related electrophysiological phenotypes: genome scans with microsatellites compared to single-nucleotide polymorphisms.

P300 amplitude is an electrophysiological quantitative trait that is correlated with both alcoholism and smoking status. Using the Collaborative Study on the Genetics of Alcoholism data, we performed model-free linkage analysis to investigate the relationship between alcoholism, P300 amplitude, and habitual smoking. We also analyzed the effect of parent-of-origin on alcoholism, and utilized both microsatellites (MS) markers and single-nucleotide polymorphisms (SNPs).

Estimating haplotype frequencies in pooled DNA samples when there is genotyping error.

Background: Maximum likelihood estimates of haplotype frequencies can be obtained from pooled DNA using the expectation maximization (EM) algorithm. Through simulation, we investigate the effect of genotyping error on the accuracy of haplotype frequency estimates obtained using this algorithm. We explore model parameters including allele frequency, inter-marker linkage disequilibrium (LD), genotyping error rate, and pool size.