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Jennifer L. Moran

Bio: Jennifer L. Moran is an academic researcher from Broad Institute. The author has contributed to research in topics: Genome-wide association study & Copy-number variation. The author has an hindex of 54, co-authored 114 publications receiving 33978 citations. Previous affiliations of Jennifer L. Moran include Scott & White Hospital & University of Illinois at Chicago.


Papers
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Journal ArticleDOI
Stephan Ripke1, Stephan Ripke2, Benjamin M. Neale1, Benjamin M. Neale2  +351 moreInstitutions (102)
24 Jul 2014-Nature
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

6,809 citations

Journal ArticleDOI
Shaun Purcell1, Shaun Purcell2, Naomi R. Wray3, Jennifer Stone2, Jennifer Stone1, Peter M. Visscher, Michael Conlon O'Donovan4, Patrick F. Sullivan5, Pamela Sklar2, Pamela Sklar1, Douglas M. Ruderfer, Andrew McQuillin, Derek W. Morris6, Colm O'Dushlaine6, Aiden Corvin6, Peter Holmans4, Stuart MacGregor3, Hugh Gurling, Douglas Blackwood7, Nicholas John Craddock5, Michael Gill6, Christina M. Hultman8, Christina M. Hultman9, George Kirov4, Paul Lichtenstein9, Walter J. Muir7, Michael John Owen4, Carlos N. Pato10, Edward M. Scolnick2, Edward M. Scolnick1, David St Clair, Nigel Williams4, Lyudmila Georgieva4, Ivan Nikolov4, Nadine Norton4, Hywel Williams4, Draga Toncheva, Vihra Milanova, Emma Flordal Thelander9, Patrick Sullivan11, Elaine Kenny6, Emma M. Quinn6, Khalid Choudhury12, Susmita Datta12, Jonathan Pimm12, Srinivasa Thirumalai13, Vinay Puri12, Robert Krasucki12, Jacob Lawrence12, Digby Quested14, Nicholas Bass12, Caroline Crombie15, Gillian Fraser15, Soh Leh Kuan, Nicholas Walker, Kevin A. McGhee7, Ben S. Pickard16, P. Malloy7, Alan W Maclean7, Margaret Van Beck7, Michele T. Pato10, Helena Medeiros10, Frank A. Middleton17, Célia Barreto Carvalho10, Christopher P. Morley17, Ayman H. Fanous, David V. Conti10, James A. Knowles10, Carlos Ferreira, António Macedo18, M. Helena Azevedo18, Andrew Kirby2, Andrew Kirby1, Manuel A. R. Ferreira2, Manuel A. R. Ferreira1, Mark J. Daly2, Mark J. Daly1, Kimberly Chambert1, Finny G Kuruvilla1, Stacey Gabriel1, Kristin G. Ardlie1, Jennifer L. Moran1 
06 Aug 2009-Nature
TL;DR: The extent to which common genetic variation underlies the risk of schizophrenia is shown, using two analytic approaches, and the major histocompatibility complex is implicate, which is shown to involve thousands of common alleles of very small effect.
Abstract: Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%(1,2). We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

4,573 citations

01 Sep 2012
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.

2,767 citations

Journal ArticleDOI
TL;DR: Clonal hematopoiesis with somatic mutations is readily detected by means of DNA sequencing, is increasingly common as people age, and is associated with increased risks of hematologic cancer and death.
Abstract: Cancers arise from multiple acquired mutations, which presumably occur over many years. Early stages in cancer development might be present years before cancers become clinically apparent. Methods We analyzed data from whole-exome sequencing of DNA in peripheral-blood cells from 12,380 persons, unselected for cancer or hematologic phenotypes. We identified somatic mutations on the basis of unusual allelic fractions. We used data from Swedish national patient registers to follow health outcomes for 2 to 7 years after DNA sampling. Results Clonal hematopoiesis with somatic mutations was observed in 10% of persons older than 65 years of age but in only 1% of those younger than 50 years of age. Detectable clonal expansions most frequently involved somatic mutations in three genes (DNMT3A, ASXL1, and TET2) that have previously been implicated in hematologic cancers. Clonal hematopoiesis was a strong risk factor for subsequent hematologic cancer (hazard ratio, 12.9; 95% confidence interval, 5.8 to 28.7). Approximately 42% of hematologic cancers in this cohort arose in persons who had clonality at the time of DNA sampling, more than 6 months before a first diagnosis of cancer. Analysis of bone marrow–biopsy specimens obtained from two patients at the time of diagnosis of acute myeloid leukemia revealed that their cancers arose from the earlier clones. Conclusions Clonal hematopoiesis with somatic mutations is readily detected by means of DNA sequencing, is increasingly common as people age, and is associated with increased risks of hematologic cancer and death. A subset of the genes that are mutated in patients with myeloid cancers is frequently mutated in apparently healthy persons; these mutations may represent characteristic early events in the development of hematologic cancers. (Funded by the National Human Genome Research Institute and others.)

2,497 citations

Journal ArticleDOI
S. Hong Lee1, Stephan Ripke2, Stephan Ripke3, Benjamin M. Neale2  +402 moreInstitutions (124)
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

2,058 citations


Cited by
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Journal Article
TL;DR: For the next few weeks the course is going to be exploring a field that’s actually older than classical population genetics, although the approach it’ll be taking to it involves the use of population genetic machinery.
Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

9,847 citations

Journal ArticleDOI
23 Jan 2015-Science
TL;DR: In this paper, a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level.
Abstract: Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

9,745 citations

Journal ArticleDOI
Monkol Lek, Konrad J. Karczewski1, Konrad J. Karczewski2, Eric Vallabh Minikel2, Eric Vallabh Minikel1, Kaitlin E. Samocha, Eric Banks2, Timothy Fennell2, Anne H. O’Donnell-Luria2, Anne H. O’Donnell-Luria1, Anne H. O’Donnell-Luria3, James S. Ware, Andrew J. Hill4, Andrew J. Hill1, Andrew J. Hill2, Beryl B. Cummings2, Beryl B. Cummings1, Taru Tukiainen1, Taru Tukiainen2, Daniel P. Birnbaum2, Jack A. Kosmicki, Laramie E. Duncan2, Laramie E. Duncan1, Karol Estrada1, Karol Estrada2, Fengmei Zhao2, Fengmei Zhao1, James Zou2, Emma Pierce-Hoffman2, Emma Pierce-Hoffman1, Joanne Berghout5, David Neil Cooper6, Nicole A. Deflaux7, Mark A. DePristo2, Ron Do, Jason Flannick1, Jason Flannick2, Menachem Fromer, Laura D. Gauthier2, Jackie Goldstein2, Jackie Goldstein1, Namrata Gupta2, Daniel P. Howrigan1, Daniel P. Howrigan2, Adam Kiezun2, Mitja I. Kurki1, Mitja I. Kurki2, Ami Levy Moonshine2, Pradeep Natarajan, Lorena Orozco, Gina M. Peloso1, Gina M. Peloso2, Ryan Poplin2, Manuel A. Rivas2, Valentin Ruano-Rubio2, Samuel A. Rose2, Douglas M. Ruderfer8, Khalid Shakir2, Peter D. Stenson6, Christine Stevens2, Brett Thomas2, Brett Thomas1, Grace Tiao2, María Teresa Tusié-Luna, Ben Weisburd2, Hong-Hee Won9, Dongmei Yu, David Altshuler10, David Altshuler2, Diego Ardissino, Michael Boehnke11, John Danesh12, Stacey Donnelly2, Roberto Elosua, Jose C. Florez2, Jose C. Florez1, Stacey Gabriel2, Gad Getz2, Gad Getz1, Stephen J. Glatt13, Christina M. Hultman14, Sekar Kathiresan, Markku Laakso15, Steven A. McCarroll2, Steven A. McCarroll1, Mark I. McCarthy16, Mark I. McCarthy17, Dermot P.B. McGovern18, Ruth McPherson19, Benjamin M. Neale2, Benjamin M. Neale1, Aarno Palotie, Shaun Purcell8, Danish Saleheen20, Jeremiah M. Scharf, Pamela Sklar, Patrick F. Sullivan14, Patrick F. Sullivan21, Jaakko Tuomilehto22, Ming T. Tsuang23, Hugh Watkins16, Hugh Watkins17, James G. Wilson24, Mark J. Daly2, Mark J. Daly1, Daniel G. MacArthur2, Daniel G. MacArthur1 
18 Aug 2016-Nature
TL;DR: The aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC) provides direct evidence for the presence of widespread mutational recurrence.
Abstract: Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.

8,758 citations

Journal ArticleDOI
19 May 2016-Blood
TL;DR: The 2016 edition of the World Health Organization classification of tumors of the hematopoietic and lymphoid tissues represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition.

7,147 citations

Journal ArticleDOI
Stephan Ripke1, Stephan Ripke2, Benjamin M. Neale2, Benjamin M. Neale1  +351 moreInstitutions (102)
24 Jul 2014-Nature
TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

6,809 citations