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- Study Description
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Important Links and Information
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- Instructions for requestors
- Data Use Certification (DUC) Agreement
- Talking Glossary of Genetic Terms
This study was designed to assess the phenotypic effects of rare variants. Rare variants are difficult to study in a high-throughput manner because most cohorts are underpowered to detect associations. In order to gain power to test rare variants, we use Phenotype Risk Scores (PheRS) based on features of Mendelian diseases. PheRS is calculated using claims data from an EHR that is mapped to clinical features from OMIM's clinical descriptions of Mendelian disease. We calculated PheRS for 1,204 Mendelians diseases in a cohort of 21,701 individuals genotyped on the HumanExome BeadChip. We then tested for association between these diseases and rare variants in causal genes.
A phenotype risk score is calculated as the weighted sum of features for a given disease. The features are defined as a set of phecodes (consolidated ICD codes) associated with a particular Mendelian disease as described in OMIM. The weights for each phecode are calculated as the log inverse prevalence of the phecode in our cohort. For an individual, their score equals the sum of the weights for each phecode that is present in their medical record.
Our study was based on a cohort of individuals with genotype data linked to de-identified electronic health records (EHR) from Vanderbilt's BioVU resource. We hope that this method will help generate phenotype-genotype correlation data on rare variants which in turn may inform rare variant interpretations use for diagnostics.
- Study Design:
- Case-Control
- Study Type:
- Cohort
- Total number of consented subjects: 21701
- Subject Sample Telemetry Report (SSTR)
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- Authorized Access
- Publicly Available Data
- Link to other NCBI resources related to this study
- Study Inclusion/Exclusion Criteria
In our cohort of 21,701 individuals of European ancestry, we included only individuals who were at least 18 years of age at their last visit recorded in the EHR. We excluded all individuals with evidence of hematological malignancies, blood transfusions, or stem cell transplants prior to the date the blood sample used for genotyping was drawn, as well as patients who visited Vanderbilt University Medical Center exclusively for cancer care.
- Molecular Data
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Type Source Platform Number of Oligos/SNPs SNP Batch Id Comment Whole Exome Genotyping Illumina Infinium HumanExome BeadChip N/A N/A - Selected Publications
- Diseases/Traits Related to Study (MeSH terms)
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- Primary Phenotype: Genetic Diseases, Inborn
- Links to Related Genes
- Authorized Data Access Requests
- Study Attribution
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Principal Investigator
- Josh Denny. Vanderbilt University Medical Center, Nashville, TN, USA.
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Co-Investigator
- Lisa Bastarache. Vanderbilt University Medical Center, Nashville, TN, USA.
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Funding Sources
- R01LM010685. National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
- K22LM011939. National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
- T15LM007359. National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
- U01HG004603. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
- U01HG006378. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
- U01HG008672. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
- UL1RR024975. National Center for Research Resources, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
- UL1TR000445. National Center for Research Resources, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
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Principal Investigator