Dataset Information

POPRES: Population Reference Sample

ABSTRACT:

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.

PROVIDER: phs000145.v2.p2 | EGA |

REPOSITORIES: EGA

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Publications

An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people.

Nelson Matthew R MR Wegmann Daniel D Ehm Margaret G MG Kessner Darren D St Jean Pamela P Verzilli Claudio C Shen Judong J Tang Zhengzheng Z Bacanu Silviu-Alin SA Fraser Dana D Warren Liling L Aponte Jennifer J Zawistowski Matthew M Liu Xiao X Zhang Hao H Zhang Yong Y Li Jun J Li Yun Y Li Li L Woollard Peter P Topp Simon S Hall Matthew D MD Nangle Keith K Wang Jun J Wang Jun J Abecasis Gonçalo G Cardon Lon R LR Zöllner Sebastian S Whittaker John C JC Chissoe Stephanie L SL Novembre John J Mooser Vincent V

Science (New York, N.Y.) 20120517 6090

Rare genetic variants contribute to complex disease risk; however, the abundance of rare variants in human populations remains unknown. We explored this spectrum of variation by sequencing 202 genes encoding drug targets in 14,002 individuals. We find rare variants are abundant (1 every 17 bases) and geographically localized, so that even with large sample sizes, rare variant catalogs will be largely incomplete. We used the observed patterns of variation to estimate population growth parameters, ...[more]

PMID: 22604722

Publication: 1/7

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Project description: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.

Dataset Information

POPRES: Population Reference Sample

Publications

An abundance of rare functional variants in 202 drug target genes sequenced in 14,002 people.

Similar Datasets

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