Browsing by Subject "SNP"

Now showing 1 - 4 of 4
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    A Bayesian Hierarchical Model with SNP-level Functional Priors Applied to a Pathway-wide Association Study.
    (2010) Huang, Weizi

    Tremendous effort has been put into study of the etiology of complex

    diseases including the breast cancer, type 2 diabetes,

    cardiovascular diseases, and prostate cancers. Despite large numbers of reported disease-associated loci,

    few associated loci have been replicated, and some true associations

    does not belong to the group of the most significant loci

    reported to be associated. We built a Bayesian hierarchical model incorporated

    with SNP-level functional data that can help identify associated SNPs in pathway-wide association studies.

    We applied the model to an association study for the serous invasive ovarian cancer based on the DNA repair and apoptosis pathways. We found that using our model, blocks of SNPs located in regions enriched for missense SNPs or gene inversions were more likely to be identified as candidates of the association.

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    Defining Ankyrin-b Syndrome: Characterization of Ankyrin-b Variants in Mice and Men and the Discovery of a Role for Ankyrin-b in Parasympathetic Control of Insulin Release
    (2009) Healy, Jane Anne

    Studies in the ankyrin-B+/- mouse reveal that ankyrin-B deficiency is associated with both the benefits of enhanced cardiac contractility and the costs of arrhythmia, early senescence, reduced lifespan, and impaired glucose tolerance. This constellation of traits is known as ankyrin-B syndrome, which may have important implications for humans possessing functional ankyrin-B mutations. We found that ankyrin-B variants are surprisingly common, ranging from 2 percent of European individuals to 8 percent in individuals from West Africa. Furthermore, by studying of the metabolic phenotype associated with ankyrin-B mouse, we have uncovered a major new dimension to ankyrin-B syndrome, a link between ankyrin-B and parasympathetic control of insulin secretion. Stimulation of pancreatic beta cells by acetylcholine augments glucose-stimulated insulin secretion by inducing inositol-trisphosphate receptor (InsP3R)-mediated Ca2+ release. We report that ankyrin-B is also enriched in pancreatic beta cells. Ankyrin-B-deficient islets display impaired potentiation of insulin secretion by the muscarinic agonist carbachol, blunted carbachol-mediated intracellular Ca2+- release, and reduced InsP3R stability. Ankyrin-B(+/-) mice also display postprandial hyperglycemia, consistent with impaired parasympathetic potentiation of glucose-stimulated insulin secretion. R1788W mutation of ankyrin-B impairs its function in pancreatic islets and associates with type 2 diabetes in Caucasians and Hispanics. Finally, we have generated knockin mice corresponding to the R1788W and L1622I mutations. Functional characterization of these animals will allow us to better understand the relationship between human ankyrin-B variants and ankyrin-B syndrome.

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    Feasibility of salivary DNA collection in a population-based case-control study: a pilot study of pediatric Crohn's disease.
    (Clinical epidemiology, 2018-01) Kappelman, Michael D; Lange, Aksel; Randell, Rachel L; Basta, Patricia V; Sandler, Robert S; Laugesen, Kristina; Byrjalsen, Anna; Christensen, Tina; Frøslev, Trine; Erichsen, Rune

    Background

    Epidemiologic studies combining exposure and outcome data with the collection of biosamples are needed to study gene-environment interactions that might contribute to the etiology of complex diseases such as pediatric Crohn's disease (CD). Nationwide registries, including those in Denmark and other Scandinavian countries, provide efficient and reliable sources of data for epidemiological studies evaluating the environmental determinants of disease. We performed a pilot study to test the feasibility of collecting salivary DNA to augment registry data in established cases of pediatric CD and randomly selected, population-based controls.

    Subjects and methods

    Cases of CD born after 1995 and residing in the central region of Denmark were identified through the Danish National Patient Registry and confirmed by using standard diagnostic criteria. Age- and gender-matched controls were selected at random through the civil registration system. Cases and controls were contacted by mail and telephone and invited to submit a saliva sample. DNA was extracted and genotyped for six CD-associated single-nucleotide polymorphisms (SNPs).

    Results

    A total of 53 cases of pediatric CD were invited, and 40 contributed a saliva sample (75% response rate). A total of 126 controls were invited, and 54 contributed a saliva sample (44% response rate). As expected, demographic characteristics did not differ between cases and controls. DNA was successfully isolated from 93 of 94 samples. Genotyping was performed with only 2% undetermined genotypes. For five of six SNPs known to be associated with CD, risk allele frequencies were higher in cases than controls.

    Conclusion

    This pilot study strongly supports the feasibility of augmenting traditional epidemiological data from Danish population-based registries with the de novo collection of genetic information from population-based cases and controls. This will facilitate rigorous studies of gene-environment interactions in complex chronic conditions such as CD.
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    Racial differences in the association of CD14 polymorphisms with serum total IgE levels and allergen skin test reactivity.
    (Journal of asthma and allergy, 2013-01) Wang, Zongyao; Sundy, John S; Foss, Catherine M; Barnhart, Huiman X; Palmer, Scott M; Allgood, Sallie D; Trudeau, Evan; Alexander, Katie M; Levesque, Marc C
    BACKGROUND: The CD14 C-159T single nucleotide polymorphism (SNP) has been investigated widely as a candidate genetic locus in patients with allergic disease. There are conflicting results for the association of the CD14 C-159T SNP with total serum immunoglobulin E (IgE) levels and atopy. There are limited data regarding the association of the CD14 C-159T SNP in subjects of African ancestry. The aim of the study was to determine whether the C-159T SNP and other CD14 SNPs (C1188G, C1341T) were associated with total serum IgE levels and with allergy skin test results in nonatopic and atopic subjects; as well as in Caucasian and African American subjects. METHODS: A total of 291 participants, 18-40 years old, were screened to determine whether they were atopic and/or asthmatic. Analyses were performed to determine the association between CD14 C-159T, C1188G, or C1341T genotypes with serum IgE levels and with the number of positive skin tests among Caucasian or African American subjects. RESULTS: We found no significant association of serum total IgE level with CD14 C-159T, C1188G, or C1341T genotypes within nonatopic or atopic subjects. Subjects with CD14-159 T alleles had significantly more positive allergen skin tests than subjects without CD14-159 T alleles (P = 0.0388). There was a significant association between the CD14 1188 G allele, but not the CD14 1341 T allele, with the number of positive skin-test results in Caucasians, but not in African Americans. CONCLUSION: These results support a possible association between CD14 polymorphisms and atopy. CD14-159 T or CD14 1188 G alleles were associated with atopic disease. For subjects with CD14 1188 G alleles, the association with atopic disease was stronger in Caucasians compared to African Americans.