1,720,977 research outputs found
Relative impact of indels versus SNPs on complex disease
Full text linkIt is unclear whether insertions and deletions (indels) are more likely to influence complex traits than abundant single‐nucleotide polymorphisms (SNPs). We sought to understand which category of variation is more likely to impact health. Using the SardiNIA study as an exemplar, we characterized 478,876 common indels and 8,246,244 common SNPs in up to 5,949 well‐phenotyped individuals from an isolated valley in Sardinia. We assessed association between 120 traits, resulting in 89 nonoverlapping‐associated loci.We evaluated whether indels were enriched among credible sets of potential causal variants. These credible sets included 1,319 SNPs and 88 indels. We did not find indels to be significantly enriched. Indels were the most likely causal variant in seven loci, including one locus associated with monocyte count where an indel with causality and mechanism previously demonstrated (rs200748895:TGCTG/T) had a 0.999 posterior probability. Overall, our results show a very modest and nonsignificant enrichment for common indels in associated loci.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147866/1/gepi22175_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147866/2/gepi22175-sup-0001-Gagliano-Supplementary.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147866/3/gepi22175.pd
Improved Analysis of Large Genetic Association Studies Using Summary Statistics
Full text linkGenome-wide association studies, which examine millions of genetic variants in thousands of individuals, have identified many complex trait associated loci. As sample sizes increase, particularly through meta-analysis, the number of disease associated loci has increased rapidly. The objective of this dissertation is to demonstrate the advantages of combining data across studies using summary statistics and to demonstrate methods that use publicly available information, such as functional annotation of the genome, to gain further insight into the genetics of human disease.
In the first project, we analyze data from 188,578 individuals using genome-wide and custom genotyping arrays to identify new loci and refine known loci for lipid traits low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and total cholesterol. We identify and annotate 157 loci associated with lipid levels at P < 5x10-8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian, and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipids are often associated with cardiovascular and metabolic traits including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio, and body mass index. Our results illustrate the value of genetic data from individuals of diverse ancestries and provide insights into biological mechanisms regulating blood lipids to guide future genetic, biological, and therapeutic research.
In the second project, we propose that causal variants for a trait may share certain genomic features. Importantly, we show that when these genomic features can be identified, we can use them to help pinpoint likely causal variants among many trait associated variants. We develop a model that identifies genomic features enriched among the associated loci and uses this information to prioritize likely functional variants in each locus leading to narrower sets of variants for follow-up. Our models work for both quantitative and case-control data and can be used with summary statistics, making it convenient to incorporate in ongoing meta-analysis of genome-wide association studies that can include 100,000s of individuals.
In the third project, we consider meta-analysis where studies may have overlapping sets of participants. In such scenarios, meta-analysis methods that do not account for overlap will perform poorly and have inflated Type I error. We propose a method to identify participant overlap between GWAS using only summary statistics, estimate the degree of overlap, and correctly meta-analyze studies taking into account the overlap. Our method builds upon and extends previous methods that allow meta-analysis of GWAS studies with known overlap proportions. We illustrate our method using simulations and artificially created overlapping samples using real GWAS data.PhDBiostatisticsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/143992/1/sebanti_1.pd
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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