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Introduction to Genetic Data in the Hrs Genetics in Thegenetics in Tutorial Summary INTRODUCTION TO GENETIC DATA IN THE HRS GENETICS IN THE IN GENETICS THE 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 Frontiers in Genomic Research HRS ROLE IN GENETIC DISCOVERY • 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 Decision to Expand into Genetics HRS ROLE IN GENETIC DISCOVERY • 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 HOW HRS IS CONTRIBUTING HRS ROLE IN GENETIC DISCOVERY • 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 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 DATA IMPUTED AND • 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 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 CANDIDATE GENE AND SNP FILES • HRS uses the genotype data to create candidate gene and SNP files • Provide data users access to carefully selected subsets of HRS genotype data • Smaller files designed for those interested in a specific gene or SNP • Two broad phenotypic-related datasets: • Cognition • Longevity • Not complete lists of genes or SNPs associated with these phenotypes; most promising from published studies EXOME DATA EXOME DATA • HRS provides exome data • Only a small percentage of genome is coded into proteins • The exome consists of the coding portion of the genome, representing “functional” part of the genome • Used in the search for genetic elements underlying phenotypic traits and diseases • Available for 15,600 samples collected 2006-2010 TELOMERE LENGTH DATA TELOMERE LENGTH DATA • Telomeres are a region at end of a chromosome that protects the chromosome from deterioration • Telomeres shorten as we age • Telomere length is a marker of cellular aging • Telomere length was measured on 5,808 samples in 2008 POLYGENIC SCORES POLYGENIC SCORES • An initial set of polygenic scores (PGSs) • Complex health outcomes or behaviors often polygenic • Can use published effect sizes from GWAS to construct a PGS • A PGS aggregates millions of loci across the human genome; weighted by strength of association with trait • Initial HRS PGSs are available in 2017 ACCESSING THE DATA MAIN GENETIC DATA PAGE DATA GENETIC MAIN WHERE TO BEGIN • Main page for genetic data • From HRS homepage—hrs.isr.umich.edu/about—click on data products and scroll to genetic data • Links to each specific data product (below) • Click on any data product GENETIC DATA DATA PAGE GENETIC WHERE TO BEGIN • This page lists • All HRS genetic data products • Description provides information on each of these products • Information on how to apply • Training opportunities • Links to additional information • A menu to the right allows you to toggle up and down • Click on the link for How to Apply APPLYING FOR HRS GENETIC DATA 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].
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