HapMap Project

HapMap Project
Name	International HapMap Project
Start	2002
End	2009
Participants	International HapMap Consortium
Location	United Kingdom; United States; China; Japan; Nigeria
Outcome	Human haplotype map; reference panels for SNP variation

HapMap Project

The HapMap Project was an international collaborative effort to create a haplotype map of common human genetic variation. It aimed to catalog single-nucleotide polymorphisms across diverse populations, enabling studies by institutions such as the Wellcome Trust, National Institutes of Health, and the International HapMap Consortium. The project linked large-scale genotyping initiatives across centers like the Broad Institute, RIKEN, and the Sanger Centre to support disease-association research in settings including the Framingham Heart Study and the International Cancer Genome Consortium.

Background and objectives

The initiative built on prior work at organizations including the Human Genome Project, the SNP Consortium, and the International HapMap Consortium to extend efforts by the National Human Genome Research Institute, the Wellcome Trust Sanger Institute, and the Whitehead Institute. Objectives included producing reference panels useful to groups such as the International HapMap Project collaborating centers, the HapMap Data Coordination Center, and population studies in locations like Beijing, Ibadan, and Tokyo. It coordinated with cohorts represented in studies from the Centers for Disease Control and Prevention, the Framingham Heart Study, and the UK Biobank, aiming to facilitate association mapping used by teams at Harvard Medical School, Stanford University, and the University of Oxford.

Methods and design

Design choices reflected technologies developed at the Broad Institute, Illumina, and Affymetrix and computational approaches from the Wellcome Trust Centre for Human Genetics, RIKEN, and the European Bioinformatics Institute. Sampling strategies included panels from populations in Nigeria (Yoruba), Japan (Tokyo), China (Beijing), Utah residents of European descent, and additional cohorts studied by the International HapMap Consortium, the Human Genome Diversity Project, and the 1000 Genomes Project. Genotyping pipelines drew on platforms from Illumina and Affymetrix, quality control frameworks used by the Sanger Institute and the National Institutes of Health, and phasing algorithms developed at institutions like Stanford University and the University of Washington. Data sharing policies paralleled practices at the Wellcome Trust, the National Institutes of Health, and the European Molecular Biology Laboratory.

Findings and results

Major outputs included catalogs of common single-nucleotide polymorphisms assembled by consortia at the Wellcome Trust Sanger Institute, the Broad Institute, and RIKEN, and haplotype blocks characterized in papers from researchers at Harvard University, the University of Oxford, and the University of Cambridge. Results informed linkage disequilibrium maps used by groups such as the International HapMap Consortium, the ENCODE project, and the 1000 Genomes Project. Empirical findings cited by teams at the Broad Institute, the Wellcome Trust, and the National Institutes of Health clarified tag SNP selection strategies employed in genome-wide association studies by the Wellcome Trust Case Control Consortium, the CHARGE consortium, and the International Parkinson Disease Genomics Consortium.

Impact on genetics and medicine

The resource accelerated genome-wide association studies conducted by the Wellcome Trust Case Control Consortium, the Framingham Heart Study, and the International COPD Genetics Network, and informed translational research at institutions such as Massachusetts General Hospital, Johns Hopkins University, and Memorial Sloan Kettering Cancer Center. Pharmaceutical research at companies collaborating with academic centers including Pfizer, GlaxoSmithKline, and Merck used HapMap-derived panels to prioritize targets later investigated in clinical trials overseen by the Food and Drug Administration and the European Medicines Agency. Public-health genetics efforts by the Centers for Disease Control and Prevention and the World Health Organization incorporated findings from analyses by Stanford University, Yale University, and the University of California, San Francisco.

Criticisms and limitations

Critiques emerged from scholars affiliated with institutions such as the Max Planck Institute, the University of Cape Town, and the American Civil Liberties Union regarding population representation and ethical oversight, echoing debates involving the Human Genome Diversity Project and the Council for International Organizations of Medical Sciences. Methodological limitations flagged by researchers at the Broad Institute, RIKEN, and the Sanger Centre included underrepresentation of rare variants later documented by the 1000 Genomes Project and the Exome Aggregation Consortium. Privacy concerns raised in discussions at the National Institutes of Health, the Wellcome Trust, and UNESCO highlighted issues also debated in forums like the Presidential Commission for the Study of Bioethical Issues.

Legacy and subsequent projects

The HapMap-era infrastructure influenced subsequent initiatives including the 1000 Genomes Project, the Exome Aggregation Consortium, and national biobanks such as UK Biobank, China Kadoorie Biobank, and All of Us Research Program. Analytical tools and reference panels developed by groups at the Broad Institute, the European Bioinformatics Institute, and the Wellcome Trust Sanger Institute became foundational for consortia like the ENCODE project, the International Cancer Genome Consortium, and the Global Alliance for Genomics and Health. Databases and resources maintained by institutions such as the National Center for Biotechnology Information, EMBL-EBI, and the International HapMap Consortium alumni networks continue to underpin research at universities including Harvard, Oxford, Stanford, and the University of Tokyo.

Category:Genetics