The Wellcome Trust Case Control Consortium (abbreviated WTCCC) is a collaboration between fifty research groups in the United Kingdom in the field of human genetics. Established in 2005, the WTCCC aims to conduct genome-wide association studies (GWASs) to shed light on the genetic architecture of common human diseases. [1] The founding chairman of the consortium was University of Oxford statistician Peter Donnelly. The consortium was funded by £9 million from the Wellcome Trust. [2] According to the consortium's website, it has identified "approximately 90" new susceptibility loci for common human diseases. [3]
The consortium's initial goal was to conduct large GWASs for eight common human diseases: tuberculosis, coronary heart disease, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, Crohn's disease and ulcerative colitis, bipolar disorder and hypertension. These GWASs included a total of 19,000 subjects, of whom 2,000 had one of the eight diseases and an additional 3,000 served as controls. [2] The study participants were genotyped using Affymetrix's GeneChip Human Mapping 500K Array Set, and genotype calling was conducted with the Chiamo algorithm. [4]
The results of the WTCCC's initial research were reported in Nature in 2007. The research identified 24 genetic association "signals" that were statistically significant at P < 5 × 10−7. [5] [6] At the time, this was the largest study ever conducted of the genetics of human diseases. [7] In announcing the study's findings at a London news conference, Donnelly said, "If you think of the genome as a very long road that you are trying to find your way along in the dark, previously we have only been able to turn lights on in a small number of places, but now we can turn on lights in a large number of places— in this case half a million lights". [8] The 2007 Nature paper was later named "paper of the year" by the Lancet , [9] and it led to the WTCCC being named "research leader of the year" by Scientific American . [10]
The International HapMap Project was an organization that aimed to develop a haplotype map (HapMap) of the human genome, to describe the common patterns of human genetic variation. HapMap is used to find genetic variants affecting health, disease and responses to drugs and environmental factors. The information produced by the project is made freely available for research.
The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust.
The Cancer Genome Project is part of the cancer, aging, and somatic mutation research based at the Wellcome Trust Sanger Institute in The United Kingdom. It aims to identify sequence variants/mutations critical in the development of human cancers. Like The Cancer Genome Atlas project within the United States, the Cancer Genome Project represents an effort in the War on Cancer to improve cancer diagnosis, treatment, and prevention through a better understanding of the molecular basis of the disease. The Cancer Genome Project was launched by Michael Stratton in 2000, and Peter Campbell is now the group leader of the project. The project works to combine knowledge of the human genome sequence with high throughput mutation detection techniques.
In genomics, a genome-wide association study, is an observational study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait. GWA studies typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major human diseases, but can equally be applied to any other genetic variants and any other organisms.
The 1000 Genomes Project, launched in January 2008, was an international research effort to establish by far the most detailed catalogue of human genetic variation. Scientists planned to sequence the genomes of at least one thousand anonymous participants from a number of different ethnic groups within the following three years, using newly developed technologies which were faster and less expensive. In 2010, the project finished its pilot phase, which was described in detail in a publication in the journal Nature. In 2012, the sequencing of 1092 genomes was announced in a Nature publication. In 2015, two papers in Nature reported results and the completion of the project and opportunities for future research.
Generation Scotland is a Biobank, a resource of biological samples and information on health and lifestyle from thousands of volunteer donors in Scotland.
In genetics, association mapping, also known as "linkage disequilibrium mapping", is a method of mapping quantitative trait loci (QTLs) that takes advantage of historic linkage disequilibrium to link phenotypes to genotypes, uncovering genetic associations.
DECIPHER is a web-based resource and database of genomic variation data from analysis of patient DNA. It documents submicroscopic chromosome abnormalities and pathogenic sequence variants, from over 25000 patients and maps them to the human genome using Ensembl or UCSC Genome Browser. In addition it catalogues the clinical characteristics from each patient and maintains a database of microdeletion/duplication syndromes, together with links to relevant scientific reports and support groups.
Zinc finger protein 300 is a protein that in humans is encoded by the ZNF300 gene. The protein encoded by this gene is a C2H2-type zinc finger DNA binding protein and a likely transcription factor.
Andrew B. Singleton is a British neurogeneticist currently working in the USA. He was born in Guernsey, the Channel Islands in 1972, where he lived until he was 18 years old. His secondary education was conducted at the Guernsey Grammar School. He earned a first class degree in Applied Physiology from Sunderland University and his PhD in neuroscience from the University of Newcastle upon Tyne where he studied the genetics of Alzheimer's disease and other dementias at the Medical Research Council (MRC) Neurochemical Pathology Unit. He moved to the United States in 1999, where he began working at the Mayo Clinic in Jacksonville, Florida studying the genetic basis of Parkinson's disease, ataxia, and dystonia. He moved to the National Institutes of Health in 2001 to head the newly formed Molecular Genetics unit within the Laboratory of Neurogenetics. In 2006 he took over as Chief of the Laboratory of Neurogenetics and became an NIH Distinguished Investigator in the intramural program at the National Institute on Aging (NIA) in 2017. In 2020 he stepped down as the Chief of the Laboratory of Neurogenetics and became the Acting Director of the newly formed Center for Alzheimer's and Related Dementias at the NIA. In 2021 he became the Director of CARD.
The Wellcome Centre for Human Genetics is a human genetics research centre of the Nuffield Department of Medicine in the Medical Sciences Division, University of Oxford, funded by the Wellcome Trust among others.
Philip Awadalla is a professor of medical and population genetics at the Ontario Institute for Cancer Research, and the Department of Molecular Genetics, Faculty of Medicine, University of Toronto. He is the National Scientific Director of the Canadian Partnership for Tomorrow's Health (CanPath), formerly the Canadian Partnership for Tomorrow Project (CPTP), and Executive Director of the Ontario Health Study. He is also the Executive Scientific Director of the Genome Canada Genome Technology Platform, the Canadian Data Integration Centre. Professor Awadalla was the Executive Scientific Director of the CARTaGENE biobank, a regional cohort member of the CPTP, from 2009 to 2015, and is currently a scientific advisor for this and other scientific and industry platforms. At the OICR, he is Director of Computational Biology.
Jonathan Laurence Marchini is a Bayesian statistician and professor of statistical genomics in the Department of Statistics at the University of Oxford, a tutorial fellow in statistics at Somerville College, Oxford and a co-founder and director of Gensci Ltd. He co-leads the Haplotype Reference Consortium.
Complex traits, also known as quantitative traits, are traits that do not behave according to simple Mendelian inheritance laws. More specifically, their inheritance cannot be explained by the genetic segregation of a single gene. Such traits show a continuous range of variation and are influenced by both environmental and genetic factors. Compared to strictly Mendelian traits, complex traits are far more common, and because they can be hugely polygenic, they are studied using statistical techniques such as quantitative genetics and quantitative trait loci (QTL) mapping rather than classical genetics methods. Examples of complex traits include height, circadian rhythms, enzyme kinetics, and many diseases including diabetes and Parkinson's disease. One major goal of genetic research today is to better understand the molecular mechanisms through which genetic variants act to influence complex traits.
In statistical genetics, linkage disequilibrium score regression is a technique that aims to quantify the separate contributions of polygenic effects and various confounding factors, such as population stratification, based on summary statistics from genome-wide association studies (GWASs). The approach involves using regression analysis to examine the relationship between linkage disequilibrium scores and the test statistics of the single-nucleotide polymorphisms (SNPs) from the GWAS. Here, the "linkage disequilibrium score" for a SNP "is the sum of LD r2 measured with all other SNPs".
Charles Nohuoma Rotimi is the Director of the Trans-National Institutes of Health (NIH) center for research in genomics and global health. He works to ensure that population genetics include genomes from African populations and founded the African Society of Human Genetics in 2003. Rotimi was instrumental in the launch of the Human Heredity and Health in Africa (H3Africa) with the NIH and the Wellcome Trust. He was elected to the National Academy of Medicine in 2018.
Emmanouil Theophilos Dermitzakis is a Greek human geneticist and professor in the Department of Genetic Medicine and Development at the University of Geneva, where he is also Director of the Health 2030 Genome Center. He is an ISI Highly Cited Researcher and an elected member of the European Molecular Biology Organization. He is a member of the Swiss Institute of Bioinformatics, where his research group is focused on the genetics and genomics of complex traits in humans. He has joined GlaxoSmithKline as Vice President, Computational Biology in R&D.
Human Heredity and Health in Africa, or H3Africa, is an initiative to study the genomics and medical genetics of African people. Its goals are to build the continent's research infrastructure, train researchers and clinicians, and to study questions of scientific and medical interest to Africans. The H3Africa Consortium was formally launched in 2012 in Addis Ababa and has grown to include research projects across 32 countries, a pan-contintental bioinformatics network, and the first whole genome sequencing of many African ethnolinguistic groups.
Human genetic clustering refers to patterns of relative genetic similarity among human individuals and populations, as well as the wide range of scientific and statistical methods used to study this aspect of human genetic variation.
Professor Patrick Francis Chinnery, FRCP, FRCPath, FMedSci, is a neurologist, clinician scientist, and Wellcome Trust Principal Research Fellow based in the Medical Research Council Mitochondrial Biology Unit and the University of Cambridge, where he is also Professor of Neurology and Head of the Department of Clinical Neurosciences.