POPRES: Population Reference Sample

POPRES version 1 and 2

Technological and scientific advances, stemming in large part from the Human Genome and HapMap projects, have made large-scale, genome-wide investigations feasible and cost-effective. These advances have the potential to dramatically impact drug discovery and development by identifying genetic factors that contribute to variation in disease risk as well as drug pharmacokinetics, treatment efficacy, and adverse drug reactions. In spite of the technological advancements, successful application in biomedical research would be limited without access to suitable sample collections. To facilitate exploratory genetic research, we have assembled a DNA resource from a large number of subjects participating in multiple studies throughout the world. This resource was initially genotyped using the Affymetrix 500K SNP panel. This project includes nearly 6,000 subjects of African American, East Asian, South Asian, Mexican, and European origin.

POPRES version 3

The discovery and development of novel drugs is challenging and with high attrition rates. Selection of the right target and optimal indications for novel therapeutics represent key decision points in this process, and are often hampered by our limited understanding of the biology of the target in humans. Building a robust body of knowledge of variation within drug target genes has in several cases increased the probability of success for novel therapeutics. Our knowledge of variation within drug target genes and their influence on traits of medical interest is still very limited. In an effort to fill this gap, we resequenced the exons of 202 known or suspected drug target genes in over 16,000 well-phenotyped individuals. A total of 863,883 bases were targeted, including 351 kb of coding and 323 kb of untranslated exon regions. The sequenced subjects included 3,381 from two studies that were part of the Population Reference Sample (POPRES) project: CoLaus (N = 2,059) and LOLIPOP (N = 1,322). Genotyping data generated through the targeted next generation sequencing is available through the dbGaP.

• Study Design:
  • Case-Control
• Study Type:
  • Population
  • Control Set
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 8012
• Subject Sample Telemetry Report (SSTR)

• BioProject
• PubMed
• MeSH
• PMC

POPRES version 1 and 2

The POPRES collection includes subjects from ten individual collections. These collections are a mix of unrelated population samples and healthy controls, and are described in Nelson et al. (PMID: 18760391).

POPRES version 3

POPRES includes unrelated subjects from two population-based studies: CoLaus (Preisig et al. 2009; PMID: 19292899) and LOLIPOP (Kooner et al. 2008; PMID: 18193046). CoLaus Study: subjects included are participants in the PsyCoLaus follow-on study of psychiatric traits and/or extremes of several selected cardiovascular disease-associated traits. There was an overlap of 460 subjects between these two selections. LOLIPOP: Subjects included are a random selection of Indian Asians or European whites selected for overlap with previous genome-wide genotyping studies, European whites selected as extremes from several cardiovascular disease-related traits and subjects of other non-European ancestry.

• Primary Phenotype: Normalcy

• POPRES Investigator (Industry)
  • Matthew R. Nelson. GlaxoSmithKline, Research Triangle Park, NC, USA.
  • Margaret G. Ehm. GlaxoSmithKline, Research Triangle Park, NC, USA.
  • Stephanie L. Chissoe. GlaxoSmithKline, Research Triangle Park, NC, USA.
  • John C. Whittaker. GlaxoSmithKline, Stevenage, UK.
  • Keith Nangle. GlaxoSmithKline, Research Triangle Park, NC, USA.
  • Jennifer Aponte. GlaxoSmithKline, Research Triangle Park, NC, USA.
• CoLaus Principle Investigator (Academia)
  • Gérard Waeber. Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
• CoLaus Co-Principle Investigator (Industry)
  • Vincent Mooser. GlaxoSmithKline, Upper Merion, PA, USA.
  • Dawn M. Waterworth. GlaxoSmithKline, Philadelphia, Pennsylvania, USA.
• CoLaus Co-Principle Investigator (Academia)
  • Peter Vollenweider. Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
• PsyCoLaus Principle Investigator
  • Martin Preisig. Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
• LOLIPOP Co-Principle Investigators
  • Jaspal S. Kooner. National Heart and Lung Institute, Imperial College London, UK.
  • John C. Chambers. Department of Epidemiology and Public Health, Imperial College London, UK.
  • Paul Elliott. Department of Epidemiology and Public Health, Imperial College London, UK.
• African American Controls Co-Principle Investigators
  • Jorge R. Oksenberg. Department of Neurology, University of California, San Francisco, CA, USA.
  • Stephen L. Hauser. Department of Neurology, University of California, San Francisco, CA, USA.
• Duke Controls Principle Investigator
  • David B. Goldstein. Center for Population Genomics and Pharmacogenetics, Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
• Duke Controls Co-Investigator
  • Anna C. Need. Center for Population Genomics and Pharmacogenetics, Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.