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Institution

Vanderbilt University

EducationNashville, Tennessee, United States
About: Vanderbilt University is a education organization based out in Nashville, Tennessee, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 45066 authors who have published 106528 publications receiving 5435039 citations. The organization is also known as: Vandy.


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Journal ArticleDOI
TL;DR: The findings suggest that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis, and a common polymorphism in the promoter of M UC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrot.
Abstract: A b s t r ac t Background The mutations that have been implicated in pulmonary fibrosis account for only a small proportion of the population risk Methods Using a genomewide linkage scan, we detected linkage between idiopathic interstitial pneumonia and a 34-Mb region of chromosome 11p15 in 82 families We then evaluated genetic variation in this region in gel-forming mucin genes expressed in the lung among 83 subjects with familial interstitial pneumonia, 492 subjects with idiopathic pulmonary fibrosis, and 322 controls MUC5B expression was assessed in lung tissue Results Linkage and fine mapping were used to identify a region of interest on the p-terminus of chromosome 11 that included gel-forming mucin genes The minor-allele of the single-nucleotide polymorphism (SNP) rs35705950, located 3 kb upstream of the MUC5B transcription start site, was present at a frequency of 34% among subjects with familial interstitial pneumonia, 38% among subjects with idiopathic pulmonary fibrosis, and 9% among controls (allelic association with familial interstitial pneumonia, P = 12×10 − 15 ; allelic association with idiopathic pulmonary fibrosis, P = 25×10 − 37 ) The odds ratios for disease among subjects who were heterozygous and those who were homozygous for the minor allele of this SNP were 68 (95% confidence interval [CI], 39 to 120) and 208 (95% CI, 38 to 1137), respectively, for familial interstitial pneumonia and 90 (95% CI, 62 to 131) and 218 (95% CI, 51 to 935), respectively, for idiopathic pulmonary fibrosis MUC5B expression in the lung was 141 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not (P<0001) The variant allele of rs35705950 was associated with up-regulation in MUC5B expression in the lung in unaffected subjects (expression was 374 times as high as in unaffected subjects homozygous for the wild-type allele, P<0001) MUC5B protein was expressed in lesions of idiopathic pulmonary fibrosis Conclusions A common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis Our findings suggest that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis (Funded by the National Heart, Lung, and Blood Institute and others)

959 citations

Journal ArticleDOI
TL;DR: A novel method to scan phenomic data for genetic associations using International Classification of Disease billing codes, which are available in most EMR systems, and develops a code translation table to automatically define 776 different disease populations and their controls using prevalent ICD9 codes derived from EMR data.
Abstract: Motivation: Emergence of genetic data coupled to longitudinal electronic medical records (EMRs) offers the possibility of phenomewide association scans (PheWAS) for disease–gene associations. We propose a novel method to scan phenomic data for genetic associations using International Classification of Disease (ICD9) billing codes, which are available in most EMR systems. We have developed a code translation table to automatically define 776 different disease populations and their controls using prevalent ICD9 codes derived from EMR data. As a proof of concept of this algorithm, we genotyped the first 6005 European–Americans accrued into BioVU, Vanderbilt’s DNA biobank, at five single nucleotide polymorphisms (SNPs) with previously reported disease associations: atrial fibrillation, Crohn’s disease, carotid artery stenosis, coronary artery disease, multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis. The PheWAS software generated cases and control populations across all ICD9 code groups for each of these five SNPs, and disease-SNP associations were analyzed. The primary outcome of this study was replication of seven previously known SNP–disease associations for these SNPs. Results: Four of seven known SNP–disease associations using the PheWAS algorithm were replicated with P-values between 2.8 × 10 −6 and 0.011. The PheWAS algorithm also identified 19 previously unknown statistical associations between these SNPs and diseases at P < 0.01. This study indicates that PheWAS analysis is a feasible method to investigate SNP–disease associations. Further evaluation is needed to determine the validity of these associations and the appropriate statistical thresholds for clinical significance. Availability: The PheWAS software and code translation table are freely available at http://knowledgemap.mc.vanderbilt.edu/research.

958 citations

Journal ArticleDOI
28 May 2009-Nature
TL;DR: The results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to the authors' knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.
Abstract: Several lines of evidence point to genetic involvement in autism spectrum disorders (ASDs), neurodevelopmental and neuropsychiatric disorders characterized by impaired verbal communication and social interaction. The clinical and genetic complexities of the condition make it difficult to identify susceptibility factors, but two related studies now present robust evidence for a genetic involvement. The first, a genome-wide association study, identifies six single-nucleotide polymorphisms strongly associated with autism. These variants lie between two genes encoding neuronal cell-adhesion molecules (cadherins 9 and 10), suggesting possible involvement in ASD pathogenesis. The second study used copy number variation screens to identify genetic variants in two major gene pathways in children with ASDs. The changes are in the ubiquitin pathway, which has previously been associated with neurological disease, and in genes for neuronal cell-adhesion molecules.

958 citations

Journal ArticleDOI
TL;DR: A circuit-based framework for understanding gene and neurotransmitter interactions in schizophrenia is developed and Nicotine enhances the output of interneurons, and might thereby contribute to its therapeutic effect in schizophrenia.

955 citations

Journal ArticleDOI
Anubha Mahajan1, Min Jin Go, Weihua Zhang2, Jennifer E. Below3  +392 moreInstitutions (104)
TL;DR: In this paper, the authors aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry.
Abstract: To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

954 citations


Authors

Showing all 45403 results

NameH-indexPapersCitations
Walter C. Willett3342399413322
Meir J. Stampfer2771414283776
John Q. Trojanowski2261467213948
Robert M. Califf1961561167961
Matthew Meyerson194553243726
Scott M. Grundy187841231821
Tony Hunter175593124726
David R. Jacobs1651262113892
Donald E. Ingber164610100682
L. Joseph Melton16153197861
Ralph A. DeFronzo160759132993
David W. Bates1591239116698
Charles N. Serhan15872884810
David Cella1561258106402
Jay Hauser1552145132683
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023141
2022540
20215,134
20205,232
20194,883
20184,649