Browsing by Author "Keating, Brendan J."

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Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height
(2011-01-07)
Lanktree, Matthew B.
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Guo, Yiran
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Murtaza, Muhammed
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Glessner, Joseph T.
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Bailey, Swneke D.
Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 x 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 x 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 x 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.
Subclinical atherosclerosis and increased risk of hearing impairment
(2015-02-01)
Fischer, Mary E.
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Schubert, Carla R.
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Nondahl, David M.
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Dalton, Dayna S.
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Huang, Guan-Hua
Objective: The study\'s purpose was to test if subclinical atherosclerosis was associated with the risk of developing HI in a large cohort of middle-aged participants. Methods: Study subjects were members of the Beaver Dam Offspring Study (BOSS), a longitudinal study of adult children of participants in the population-based Epidemiology of Hearing Loss Study (1993-present). BOSS examinations took place in 2005-2008 (baseline) and 2010-2013 (5-year follow-up). The 5-year incidence of hearing impairment was defined as a pure-tone average (PTA) of thresholds at 0.5, 1, 2 and 4 kHz > 25 dB Hearing Level (dB HL) in either ear at follow-up among participants at risk (baseline PTA in both ears < = 25 dB HL; n = 2436, mean age = 47.7 years). Atherosclerosis was measured as the mean carotid intima-media thickness and the presence of carotid artery plaque. Results: Among the 1984 participants at-risk with a follow-up audiometric examination, the 5-year incidence of hearing impairment was 8.3% (95% Confidence Interval (C.I.) 7.1, 9.5). With multivariable adjustment, carotid intima- media thickness was positively associated with hearing impairment incidence (Relative Risk (RR) = 1.14 per 0.1 mm, 95% C.I. 1.04, 1.24). The number of sites (0-6) with plaque was also positively associated with the incidence of impairment (RR = 1.16 per site, 95% C.I. 1.01, 1.32). Conclusion: Atherosclerosis was associated with the 5-year incidence of hearing impairment in this predominantly middle-aged cohort. Interventions targeting atherosclerosis prevention may help to prevent or delay the onset of hearing impairment. (C) 2014 Elsevier Ireland Ltd. All rights reserved.