Biomedical subjects

Denise Daley

Publications and source records attributed to Denise Daley.

6 recordsLinked to original sources

PubMed2005

A comparison of five methods for selecting tagging single-nucleotide polymorphisms.

Our goal was to compare methods for tagging single-nucleotide polymorphisms (tagSNPs) with respect to the power to detect disease association under differing haplotype-disease association models. We were also interested in the effect that SNP selection samples, consisting of either cases, controls, or a mixture, would have on power. We investigated five previously described algorithms for choosing tagSNPS: two that picked SNPs based on haplotype structure (Chapman-haplotypic and Stram), two that picked SNPs based on pair-wise allelic association (Chapman-allelic and Cousin), and one control method that chose equally spaced SNPs (Zhai). In two disease-associated regions from the Genetic Analysis Workshop 14 simulated data, we tested the association between tagSNP genotype and disease over the tagSNP sets chosen by each method for each sampling scheme. This was repeated for 100 replicates to estimate power. The two allelic methods chose essentially all SNPs in the region and had nearly optimal power. The two haplotypic methods chose about half as many SNPs. The haplotypic methods had poor performance compared to the allelic methods in both regions. We expected an improvement in power when the selection sample contained cases; however, there was only moderate variation in power between the sampling approaches for each method. Finally, when compared to the haplotypic methods, the reference method performed as well or worse in the region with ancestral disease haplotype structure.

Genetic Techniques↗

PubMed2005

Approaches to the study of inflammatory gene haplotypes and susceptibility to cardiac, vascular and pulmonary diseases.

Haplotype association methods are increasingly being used in the study of complex diseases to better understand and correlate genetic polymorphisms with cardiovascular and pulmonary disease phenotypes and drug responses. Understanding of the human genome is rapidly expanding; how this knowledge is impacting the determination of haplotypes and how they can be utilized in the study of complex diseases is reviewed. Applied and methodological fields are discussed and examples of how haplotypes are used to study complex diseases in this modern era are provided.

Cardiovascular Diseases↗

PubMed2003

Interaction of gender and body mass index (BMI) reveals evidence of linkage for hypertension in the Framingham Heart Study.

BACKGROUND: Genetic heterogeneity and complex biologic mechanisms of blood pressure regulation pose significant challenges to the identification of susceptibility loci influencing hypertension. Previous linkage studies have reported regions of interest, but lack consistency across studies. Incorporation of covariates, in particular the interaction between two independent risk factors (gender and BMI) greatly improved our ability to detect linkage. RESULTS: We report a highly significant signal for linkage to chromosome 2p, a region that has been implicated in previous linkage studies, along with several suggestive linkage regions. CONCLUSION: We demonstrate the importance of including covariates in the linkage analysis when the phenotype is complex.

Body Mass Index↗

PubMed2003

A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2.

Colorectal cancer is the second most leading cause of cancer death among adult Americans. Two autosomal dominant hereditary forms of the disease, familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, together account for perhaps 5% of all cases. However, in approximately 20% of additional colon cancer cases, the affected individuals report a family history of colon cancer in a first-degree relative. Similar familial clusters of colon cancer and early-onset colon adenomas have also been reported. To determine whether such familial aggregations arise by chance or reflect a hereditary colon cancer susceptibility, we conducted a whole genome scan to test for genetic linkage in 53 kindreds in which two or more siblings were affected by age 65 or younger with colon cancer or with advanced colon adenomas that were >1 cm in size or that showed high-grade dysplasia. In this cohort we found genetic linkage of disease (P = 0.00045) to chromosomal region 9q22.2-31.2 in a pattern consistent with autosomal dominant disease alleles. These data suggest that a single locus can contribute to disease susceptibility in a subset of patients with nonsyndromic forms of familial colorectal neoplasia.

Alleles↗

PubMed2003

Effects of covariates: a summary of Group 5 contributions.

This report summarizes the contributions of Genetic Analysis Workshop 13 (GAW13) related to the use of covariates in genetic analysis. Seven papers are summarized, five of which analyzed the Framingham Heart Study Data, and two the simulated data. Five papers examined the role of covariates in linkage analysis, using a variety of statistical approaches including affected sibling pair analysis, conditional logistic regression, and variance components methods. One paper examined the impact of covariates on family-based association analysis. In each of these papers, the detection of genetic effects could be influenced by the incorporation of covariates. The final paper examined the role of transmission ratio distortion in the analysis of complex traits and the role of covariates in the variability in transmission ratio distortion. While each paper takes a different approach to the genetic analysis of complex traits, a common thread running through each is that the inclusion of covariates can have a substantial impact on the results of the analysis. Care must be taken to understand how the covariates are being used in each analysis, what assumptions are being made, and how these assumptions might affect the results and their interpretation. Finally, the results of Group 5 studies show that inclusion of covariates can increase the power to detect genes for complex traits, and has the potential to advance an understanding of the role of genes in these complex traits.

Cardiovascular Diseases↗

PubMed2003

Risk factors associated with delayed thyrotropin elevations in congenital hypothyroidism.

OBJECTIVES: To identify risk factors associated with delayed thyrotropin elevations in cases of congenital hypothyroidism. To determine whether routine rescreening of babies who have very low birth weight (VLBW) and babies in the neonatal intensive care unit is justified. STUDY DESIGN: Retrospective review of the New England Newborn Screening database (January 1989-June 2002) of newborns screened for hypothyroidism to determine the incidence of congenital hypothyroidism associated with delayed thyrotropin elevations and to characterize features associated with delayed thyrotropin elevations in newborns with VLBW and non-VLBW (NVLBW). RESULTS: The incidence of hypothyroidism was 14-fold higher for newborns with VLBW (1:250) compared with newborns with NVLBW (1:3500). Of the newborns with VLBW, two thirds were not detectable on the initial screening specimen. Among newborns with VLBW with delayed thyrotropin elevation, iodine exposure was found in 23%. Among newborns with NVLBW, 45% had congenital cardiac anomalies. For every 20 NVLBW cases of congenital hypothyroidism detectable by initial screening specimen, one additional case was detected with delayed thyrotropin elevation. CONCLUSIONS: Routine rescreening of babies with VLBW and babies in the neonatal intensive care unit is justified, and particular attention to follow-up testing of newborns known to have cardiac disease is warranted.

Age Factors↗