INTRODUCTION TO GENETIC DATA IN THE HRS GENETICS IN THEGENETICS IN TUTORIAL SUMMARY
• Frontiers in genomic
research and the HRS role HRS in genetic discovery • Data collection and genotyping • Data products • How to apply THE HRS ROLE IN GENETIC DISCOVERY THE THE
Frontiers in Genomic Research HRS ROLE IN GENETIC DISCOVERY GENETIC IN ROLE • Discovery of the sequence of the human genome was a major step in human genetic discovery • Areas for future research: • Identifying variations in DNA sequence and significance • Most common type of genetic variation is a single nucleotide polymorphism or SNP (pronounced “snip”) • May help predict risk of particular diseases and response to certain treatments or medications • Gene X Environment interaction studies • Understanding how the genotype (instructions coded in DNA) interacts with our environment to create our appearance, behavior, and functioning – phenotype • Change over time • Telomeres THE THE
The Decision to Expand into Genetics HRS ROLE IN GENETIC DISCOVERY GENETIC IN ROLE • Understood value of integrating direct measures of basic biology, but difficult • In 2006, a new “enhanced” in-person interview collected measures of physical function, blood-based biomarkers, and DNA samples • Collection and genotyping made possible by rapid development in genotyping and funding through the American Recovery and Reinvestment Act • March 2012, HRS genetic resource established with initial sample of 12,500 people measured on 2.5 million SNPs THE THE
HOW HRS IS CONTRIBUTING HRS ROLE IN GENETIC DISCOVERY GENETIC IN ROLE • HRS is playing a large role in the integration of genetic and social science data • HRS has many advantages: • A nationally representative sample with large samples of African Americans and Hispanics • Comparability • Longitudinal measurement • Huge selection of phenotypic measurement COLLECTING AND STORING DNA COLLECTING AND STORING STORING AND COLLECTING DATA COLLECTION
• Saliva collected during core interview for buccal (cheek) cells • Mouthwash (2006) • Oragene (2008 on) • Collection kits sent to a lab for extraction, isolation, and DNA purification • Genotyping performed at the NIH Center for Inherited Disease Research (CIDR) DATA STORAGE AND DISTRIBUTION
• Because of large size and sensitivity, genotype data are stored and distributed by the database of Genotypes and Phenotypes or dbGaP • dbGaP is part of the NIH’s National Center for Biotechnology Information • Other HRS genetic data products can be downloaded from the HRS website • Describe each product and how to access HRS GENETIC DATA PRODUCTS GENOTYPED GENOTYPED AND IMPUTED DATA
• Measure 2.5 million SNPs along the genome using the
Illumina HumanOmni 2.5M BeadChip AND IMPUTED DATA • Impute up to 22 million SNPs PER INDIVIDUAL using the 1,000 Genomes Reference Panels • Imputation increases available markers and makes possible comparisons across platforms that do not assay the same genome-wide snip panel • Used for Genome Wide Association Study (GWAS) • Examination of many genetic variants in different individuals to see if any variant is associated with a disease or trait WHAT’S AVAILABLE WHAT’S AVAILABLE?
• Version 1 - 12,500+ samples (2006 + 2008) • 1,136 Hispanic • 1,665 African-American • Measured SNPs and imputations • Genotyping used Illumina HumanOmni 2.5M Quad BeadChip and Illumina Human Exome BeadChip v1.1 • Version 2 - 15,600+ samples (2006-2010) • Expansion of minority sample and half of new cohort (2010) • Genotyping used the Illumina HumanOmni 2.5M Exome-8 with a combination of 2.5M BeadChip and Exome v1.2 • Version 3 – 18,900+ samples (2006-2012) –forthcoming • Additional expansion of minority sample and second half of new cohort • Same genotyping method as version 2 DBGAP DATABASE OF GENOTYPES AND PHENOTYPES
• These data products are available through the dbGaP website: http://www.ncbi.nlm.nih.gov/gap • Data are free, but an application is required • Raw genotype data and imputed data • Phenotype data limited so respondents cannot be identified but specific enough to verify proper data download by running preliminary association tests • Cross reference files help researchers link to HRS phenotype measures that are not in dbGaP • HRS controls access to cross-reference files • Available to all users with dbGaP approval CANDIDATE GENES FILES related datasets:related - Cognition Longevity
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Not complete lists of lists or of with Not genes complete SNPs associated these most phenotypes; promising from published studies Two broad phenotypic broad Two Provide data users access to carefully selected subsets data HRS genotype of in a specific interested for those designed files Smaller or gene SNP HRS uses data the genotype to create candidate gene and SNP files
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CANDIDATE CANDIDATE SNP AND GENE EXOME DATA 2010 samplescollected 2006-
Available for 15,600 Used inUsed the search for underlyinggenetic elements traitsphenotypic and diseases The exome consists of the coding portion of the portioncoding of the of consists exome The “functional”part of the genome representing genome, HRS provides exome data into is coded genome of a small percentageOnly proteins
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• EXOME DATA TELOMERE LENGTH DATA LENGTH DATA LENGTH
Telomere length was on samples in measured 5,808 2008 Telomeres shorten as we age cellulara markeraging of is length Telomere Telomeres are a Telomeres region at of end thata chromosome from deterioration chromosome the protects
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• TELOMERE POLYGENIC SCORES
omplex health outcomes or or outcomes health polygenic omplex often behaviors A PGS aggregates millions of loci across the human human the of loci millions across aggregates A PGS of strengthby association weighted with genome; trait Initial HRS are PGSs available in 2017 Can use published effect sizes from from to sizes GWAS construct effect Can published use a PGS An initial An initial scores (PGSs) set of polygenic C
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• POLYGENIC SCORES ACCESSING THE DATA MAIN GENETIC DATA PAGE click click — genetic data hrs.isr.umich.edu/about — and scroll scroll to and on any data any product on ain page for ain for page data genetic
Links to to Links data product (below) each specific Click From HRS homepage M on data products
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• WHERE TO BEGIN GENETIC DATA PAGE escription provides informationofon each these products D Information on how to apply how on Information opportunities Training additionalinformation to Links All HRS genetic data products data genetic HRS All •
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A menu to the right allows you to toggle up and down up and down toggle you to allows right menu the to A Apply to How for theon link Click This page lists page This
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APPLYING FOR HRS GENETIC DATA APPLYING APPLYING FOR HRS GENETIC DATA TRAINING OPPORTUNITIES TRAINING OPPORTUNITIESTRAINING ADDITIONAL INFORMATION ADDITIONAL INFORMATIONADDITIONAL This ends the web tutorial providing information on genetic data in the HRS This tutorial was produced at the University of Michigan with funding from the National Institute on Aging Comments and questions may be sent to [email protected]