Embed Size (px)
Citation preview
NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS)
Amanda KuzmaPenn Neurodegeneration Genomics Center
Department of Pathology and Laboratory MedicineUniversity of Pennsylvania Perelman School of Medicine
Outline
• Overview of NIAGADS• Data Storage Site- www.niagads.org• Data Sharing Service (DSS)- dss.niagads.org• Returning data generated from NACC samples back to ADRCs• Alzheimer’s Genomics Database- www.niagads.org/genomics
About NIAGADS
• NIAGADS is the NIA-designated data repository for AD genetics• Receive / organize data
• Develop IT infrastructure for data sharing
• Collect Institutional Certification forms; split data files by consent
• Assist with Data Access Request (DAR) review conducted by NIA ADRD Data Access
Committee (NADAC)
• Assist ADGC with data management/sharing and deposition into NIAGADS• Data coordinating center for the Alzheimer’s Disease Sequencing Project
(ADSP)www.niagads.org
Available Data and AccessData Types:
• GWAS• exome chip• summary statistics• expression
Data Access:• P-values from summary
statistics are available freely for download or viewable through the Genomics database
• All other data require a formal application
www.niagads.org
New Dataset Collection Highlights
IGAP 2019 Rare Variant Analysis• Summary Statistics (NG00075)• 14 ADGC new GWAS datasets (4/14
posted) including ADC genotypingrounds 4-7
• 5,073 NACC samples from ADC4-7 (NG00068-71)
New Dataset Collection Highlights
IGAP 2017 Exome Chip Analysis• IGAP summary statistics (in progress)• 5 ADGC exome chip datasets
• 7,711 NACC samples (NG00079+81)
NIAGADS Data Sharing Service (DSS)August 2018: 4,789 genomes• Alzheimer’s Disease Sequencing
Project Discovery/Extension WGS• ADNI WGS
Available Data Types:• Project level VCF available for free
download• GVCFs and CRAMs are available• Genome build 38
Next Data Releases:• ~20,000 whole exomes in summer• ~19,000 whole genomes in winter
dss.niagads.org
DSS Data Access Workflow
DSS Application Instructions
dss.niagads.org
Return of NACC genetic data to ADRCs ADGC Data Return- GWAS, Exome Chip, and Imputation (1000 Genomes/HRC) are returned through NACCADSP Data Return- Whole Genome/Exome data (CRAM, gVCF, pVCF) are returned through UPenn
ADSP Data Return ADRC Instructions
Or go directly to: https://www.niagads.org/adsp/content/instructions-adcs
Available NACC sequencing data for request
Currently Available for Request:• 3,262 NACC whole-exomes from
ADSP Discovery Phase• 1,154 NACC whole-genomes from
ADSP Discovery Extension Case/Control
Available in Mid-Late 2019:• 1,333 NACC whole-exomes from
ADGC AA • ~4,480 NACC whole-genomes from
ADSP related follow-up sequencing
Questions? Send us an email: [email protected]
Outline
• Overview of NIAGADS• Data Storage Site- www.niagads.org• Data Sharing Service (DSS)- dss.niagads.org• Returning data generated from NACC samples back to ADRCs• Alzheimer’s Genomics Database: www.niagads.org/genomics
NIAGADS
Alzheimer’s Genomics Database
Emily Greenfest-AllenPenn Neurodegeneration Genomics CenterPenn Institute for Biomedical InformaticsDepartment of GeneticsUniversity of Pennsylvania Perelman School of Medicine
www.niagads.org/genomics
NIAGADS GenomicsDB – www.niagads.org/genomics
NIAGADS GWAS summary statistics datasets
Alzheimer’s Disease Sequencing Project (ADSP) variants / annotations/ meta-analysis results
Variants
dbSNPNHGRI GWAS CatalogSnpEff variant annotation/LOF1000 Genomes Allele frequenciesExAC Allele frequencies
Genes
GENCODE Reference GenomeEnsembl Gene/Exon/Transcript AnnotationKEGG PathwaysGene OntologyUniProt GO AssociationsHGNC Gene Annotation
Functional Genomics
FANTOM5ENCODE
Explore AD-risk associated variants and genes.
Making these data both accessible and interpretable.
Learn more about the role these genes and variants may play in AD.
An interactive knowledge basefor AD genetics.
NIAGADS GenomicsDB – www.niagads.org/genomics
Just go to www.niagads.org/genomics
Lambert et al. (2013) is one of our highlighted datasets.
Exploring this dataset……provides you with several suggestions for moving forward.
Other possibilities? Select Search in the navigation menu to explore 14 other datasets, including several from ADGC and IGAP, which use NACC samples.
Learn more about the top IGAP (2013) SNPs
NIAGADS GenomicsDB – www.niagads.org/genomics
Just go to www.niagads.org/genomics
Lambert et al. (2013) is one of our highlighted datasets.
Exploring this dataset……provides you with several suggestions for moving forward.
Learn more about the top IGAP (2013) SNPs
Are there any IGAP SNPs in a locus of interest to me?
NIAGADS GenomicsDB – www.niagads.org/genomics
View the top-scoring SNPs in a region.
What more can I learn?
Get more information about a variant
Add more tracksGene: ABCA7ADSP WGS: yes; intron variantADGC Subset – how does it compare?
Learn more about the top IGAP (2013) SNPs
Are there any IGAP SNPs in a locus of interest to me?
NIAGADS GenomicsDB – www.niagads.org/genomics
Just go to www.niagads.org/genomics
Lambert et al. (2013) is one of our highlighted datasets.
Exploring this dataset……provides you with several suggestions for moving forward.
Learn more about the top IGAP (2013) SNPs
Are there any IGAP SNPs in a locus of interest to me?
But what if I don’t have a particular locus in mind?
Browse the SNPs highlighted in the paper…
NIAGADS GenomicsDB – www.niagads.org/genomics
Get a tabular report of these variants…… and sort, download, or share an annotated list of the published top IGAP (2013) variants.
What more can I learn?
Which of these variants have been flagged and functionally annotated by the ADSP?
Are any coding variants? What are their relative deleteriousness?
How can I learn more?
Learn more about the top IGAP (2013) SNPs
Browse the SNPs highlightedin the paper…
NIAGADS GenomicsDB – www.niagads.org/genomics Learn more about a variant.
Click on a variant in the genome browser.
Click on a variant in a search result.
Just go to www.niagads.org/genomics
…to browse, bookmark, download, search, or shareall the AD-related information we have about a specific variant.
Has this variant been flagged and functionally annotated by the ADSP?
To which traits, phenotypes, or diseases has this variant been linked through GWAS?
Is it a coding variant? What is its relative deleteriousness?
NIAGADS GenomicsDB – www.niagads.org/genomics
Click on a gene in the genome browser.
Click on a gene in a search result.
Just go to www.niagads.org/genomics
…to browse, bookmark, download, search, or shareall the AD-related information we have about a specific gene.
Learn more about a gene.
Is there any genetic evidence for association between this gene and AD?
What is known about the role this gene plays in biological and molecular processes?
To which traits, phenotypes, or diseases has this gene been linked through GWAS?
AcknowledgementsNIAGADS (UPenn)Li-San WangBriana VogelOtto ValladaresEmily Greenfest-AllenHeather IssenZivadin KatanicConor KlamannYi ZhaoYi-Fan Chou
Prabhakaran GangadharanLiming QuHannah LinAndrew WilkLaura CantwellFanny LeungAdam NajChristian J. Stoeckert Jr.Gerard Schellenberg
Collaborators:NCRADNACCGCADADSPADGCCHARGEIGAP
NIAGADS is funded by NIA U24AG041689
Penn Medicine Academic Computing (PMACS)
