scispace - formally typeset
Search or ask a question
Institution

QIMR Berghofer Medical Research Institute

Facility Brisbane, Queensland, Australia
About:QIMR Berghofer Medical Research Institute is a facility organization based out in Brisbane, Queensland, Australia. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 3790 authors who have published 11850 publications receiving 673249 citations. The organization is also known as: Queensland Institute of Medical Research & QIMR Berghofer.


Papers
More filters
Journal Article DOI

[...]

27 Jun2002 - Nature
TL;DR:BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers, with a single substitution (V599E) accounting for 80%.
Abstract:Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.

9,162citations

Journal Article DOI

[...]

08 Oct2009 - Nature
TL;DR:This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
Abstract:Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.

7,195citations

Journal Article DOI

[...]

TL;DR:The GCTA software is a versatile tool to estimate and partition complex trait variation with large GWAS data sets and focuses on the function of estimating the variance explained by all the SNPs on the X chromosome and testing the hypotheses of dosage compensation.
Abstract:For most human complex diseases and traits, SNPs identified by genome-wide association studies (GWAS) explain only a small fraction of the heritability. Here we report a user-friendly software tool called genome-wide complex trait analysis (GCTA), which was developed based on a method we recently developed to address the “missing heritability” problem. GCTA estimates the variance explained by all the SNPs on a chromosome or on the whole genome for a complex trait rather than testing the association of any particular SNP to the trait. We introduce GCTA's five main functions: data management, estimation of the genetic relationships from SNPs, mixed linear model analysis of variance explained by the SNPs, estimation of the linkage disequilibrium structure, and GWAS simulation. We focus on the function of estimating the variance explained by all the SNPs on the X chromosome and testing the hypotheses of dosage compensation. The GCTA software is a versatile tool to estimate and partition complex trait variation with large GWAS data sets.

4,497citations

Journal Article DOI

[...]

Shaun Purcell1 ,Shaun Purcell2 ,Naomi R. Wray3 ,Jennifer Stone1 ,Jennifer Stone2 ,Peter M. Visscher ,Michael Conlon O'Donovan4 ,Patrick F. Sullivan5 ,Pamela Sklar1 ,Pamela Sklar2 ,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 ,乔治基洛夫4 ,Paul Lichtenstein8 ,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 Thelander8 ,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. Daly1 ,Mark J. Daly2 ,Kimberly Chambert2 ,Finny G Kuruvilla2 ,Stacey Gabriel2 ,Kristin G. Ardlie2 ,Jennifer L. Moran2
06 Aug2009 - 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:精神分裂症是一种严重的精神障碍与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.

4,174citations

Journal Article DOI

[...]

Luke Jostins1 ,Stephan Ripke2 ,Rinse K. Weersma3 ,Richard H. Duerr4 ,Dermot P.B. McGovern5 ,Ken Y. Hui6 ,James Lee7 ,L. Philip Schumm8 ,Yashoda Sharma6 ,Carl A. Anderson1 ,Jonah Essers9 ,Mitja Mitrovic3 ,Kaida Ning6 ,Isabelle Cleynen10 ,Emilie Theatre11 ,Sarah L. Spain12 ,Soumya Raychaudhuri9 ,菲利普Goyette13 ,Zhi Wei14 ,Clara Abraham6 ,Jean-Paul Achkar15 ,Tariq Ahmad16 ,Leila Amininejad17 ,Ashwin N. Ananthakrishnan9 ,Vibeke Andersen18 ,Jane M. Andrews19 ,Leonard Baidoo4 ,Tobias Balschun20 ,Peter A. Bampton21 ,Alain Bitton22 ,Gabrielle Boucher13 ,Stephan Brand23 ,Carsten Büning24 ,Ariella Cohain25 ,Sven Cichon26 ,Mauro D'Amato27 ,Dirk De Jong3 ,Kathy L Devaney9 ,Marla Dubinsky5 ,Cathryn Edwards28 ,David Ellinghaus20 ,Lynnette R. Ferguson29 ,Denis Franchimont17 ,Karin Fransen3 ,Richard B. Gearry30 ,Michel Georges11 ,Christian Gieger ,Jürgen Glas22 ,Talin Haritunians5 ,Ailsa Hart31 ,Christopher J. Hawkey32 ,Matija Hedl6 ,Xinli Hu9 ,Tom H. Karlsen33 ,秘鲁首都利马Kupčinskas34 ,Subra Kugathasan35 ,Anna Latiano36 ,Debby Laukens37 ,Ian C. Lawrance38 ,Charlie W. Lees39 ,Edouard Louis11 ,Gillian Mahy40 ,John C. Mansfield41 ,Angharad R. Morgan29 ,Craig Mowat42 ,William G. Newman43 ,Orazio Palmieri36 ,Cyriel Y. Ponsioen44 ,Uroš Potočnik45 ,Natalie J. Prescott6 ,Miguel Regueiro4 ,Jerome I. Rotter5 ,Richard K Russell46 ,Jeremy D. Sanderson47 ,Miquel Sans ,Jack Satsangi39 ,Stefan Schreiber20 ,Lisa A. Simms48 ,Jurgita Sventoraityte34 ,Stephan R. Targan ,Kent D. Taylor5 ,Mark Tremelling49 ,Hein W. Verspaget50 ,Martine De Vos37 ,Cisca Wijmenga3 ,David C. Wilson39 ,Juliane Winkelmann51 ,Ramnik J. Xavier9 ,Sebastian Zeissig20 ,Bin Zhang25 ,Clarence K. Zhang6 ,Hongyu Zhao6 ,Mark S. Silverberg52 ,Vito Annese ,Hakon Hakonarson53 ,Steven R. Brant54 ,Graham L. Radford-Smith55 ,Christopher G. Mathew12 ,John D. Rioux13 ,Eric E. Schadt25 ,Mark J. Daly2 ,Andre Franke20 ,Miles Parkes7 ,Severine Vermeire10 ,Jeffrey C. Barrett1 ,Judy H. Cho6
Wellcome Trust Sanger Institute 1,Broad Institute 2,University of Groningen 3,University of Pittsburgh 4,Cedars-Sinai Medical Center 5,Yale University 6,University of Cambridge 7,University of Chicago 8,Harvard University 9,Katholieke Universiteit Leuven 10,University of Liège 11,King's College London 12,Université de Montréal 13,New Jersey Institute of Technology 14,Cleveland Clinic 15,Peninsula College of Medicine and Dentistry 16,Université libre de Bruxelles 17,Aarhus University 18,University of Adelaide 19,University of Kiel 20,Flinders University 21,McGill University 22,Ludwig Maximilian University of Munich 23,查利特 24,Icahn School of Medicine at Mount Sinai 25,University of Bonn 26,Karolinska Institutet 27,Torbay Hospital 28,University of Auckland 29,Christchurch Hospital 30,Imperial College London 31,Queen's University 32,University of Oslo 33,Lithuanian University of Health Sciences 34,Emory University 35,Casa Sollievo della Sofferenza 36,Ghent University 37,University of Western Australia 38,University of Edinburgh 39,Queensland Health 40,Newcastle University 41,University of Dundee 42,University of Manchester 43,University of Amsterdam 44,University of Maribor 45,Royal Hospital for Sick Children 46,Guy's and St Thomas' NHS Foundation Trust 47,QIMR Berghofer Medical Research Institute 48,Norfolk and Norwich University Hospital 49,Leiden University 50,Technische Universität München 51,University of Toronto 52,University of Pennsylvania 53,Johns Hopkins University 54,University of Queensland 55
01 Nov2012 - Nature
TL;DR:A meta-analysis of Crohn’s disease and ulcerative colitis genome-wide association scans is undertaken, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls.
Abstract:克罗恩病和溃疡性结肠炎,两家有限公司mmon forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

3,586citations


Authors

Showing all 3790 results

Name H-index Papers Citations
Nicholas G. Martin 192 1770 161952
Stephen V. Faraone 188 1427 140298
Arthur W. Toga 159 1184 109343
Grant W. Montgomery 157 926 108118