Institution
Broad Institute
Nonprofit•Cambridge, Massachusetts, United States•
About: Broad Institute is a nonprofit organization based out in Cambridge, Massachusetts, United States. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 6584 authors who have published 11618 publications receiving 1522743 citations. The organization is also known as: Eli and Edythe L. Broad Institute of MIT and Harvard.
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01 Mar 2013
TL;DR: A mutational signature defined by a high prevalence of A>C transversions at AA dinucleotides is identified and the potential activation of the RAC1 pathway is suggested as a contributor to EAC tumorigenesis.
Abstract: National Human Genome Research Institute (U.S.) (Large Scale Sequencing Program Grant U54 HG003067)
598 citations
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TL;DR: It is shown that activation of the ERK and phosphatidylinositol 3-kinase (PI3K) signaling pathways cooperate to transform human cells and suggest a mechanism for NF-kappaB activation in breast cancer, implicate the NF- kappaB pathway as a downstream mediator of PI3K, and provide a framework for integrated genomic approaches in oncogene discovery.
598 citations
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TL;DR: The role of host genetic variation in shaping the composition of the human microbiome is highlighted, and the results provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.
Abstract: Background: The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Results: Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Conclusions: Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.
598 citations
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Broad Institute1, Boston Children's Hospital2, University of Michigan3, Ludwig Maximilian University of Munich4, Brigham and Women's Hospital5, Harvard University6, National Institutes of Health7, Lund University8, United States Department of Health and Human Services9, Helsinki University Central Hospital10, University of Helsinki11, Wellcome Trust Sanger Institute12, University of North Carolina at Chapel Hill13
TL;DR: A meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs found 10 newly identified and two previously reported loci were strongly associated with variation in height, and highlight several pathways as important regulators of human stature.
Abstract: Identification of ten loci associated with height highlights new biological pathways in human growth
598 citations
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TL;DR: The results demonstrate the importance of understanding host–microbe interactions to gain better insight into human health and demonstrate the influence of host genetics on microbial species, pathways and gene ontology categories on the basis of metagenomic sequencing in 1,514 subjects.
Abstract: The gut microbiome is affected by multiple factors, including genetics. In this study, we assessed the influence of host genetics on microbial species, pathways and gene ontology categories, on the basis of metagenomic sequencing in 1,514 subjects. In a genome-wide analysis, we identified associations of 9 loci with microbial taxonomies and 33 loci with microbial pathways and gene ontology terms at P < 5 × 10-8. Additionally, in a targeted analysis of regions involved in complex diseases, innate and adaptive immunity, or food preferences, 32 loci were identified at the suggestive level of P < 5 × 10-6. Most of our reported associations are new, including genome-wide significance for the C-type lectin molecules CLEC4F-CD207 at 2p13.3 and CLEC4A-FAM90A1 at 12p13. We also identified association of a functional LCT SNP with the Bifidobacterium genus (P = 3.45 × 10-8) and provide evidence of a gene-diet interaction in the regulation of Bifidobacterium abundance. Our results demonstrate the importance of understanding host-microbe interactions to gain better insight into human health.
597 citations
Authors
Showing all 7146 results
Name | H-index | Papers | Citations |
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Eric S. Lander | 301 | 826 | 525976 |
Albert Hofman | 267 | 2530 | 321405 |
Frank B. Hu | 250 | 1675 | 253464 |
David J. Hunter | 213 | 1836 | 207050 |
Kari Stefansson | 206 | 794 | 174819 |
Mark J. Daly | 204 | 763 | 304452 |
Lewis C. Cantley | 196 | 748 | 169037 |
Matthew Meyerson | 194 | 553 | 243726 |
Gad Getz | 189 | 520 | 247560 |
Stacey Gabriel | 187 | 383 | 294284 |
Stuart H. Orkin | 186 | 715 | 112182 |
Ralph Weissleder | 184 | 1160 | 142508 |
Chris Sander | 178 | 713 | 233287 |
Michael I. Jordan | 176 | 1016 | 216204 |
Richard A. Young | 173 | 520 | 126642 |