Yumi Jin

The NCBI dbGaP database of genotypes and phenotypes

The National Center for Biotechnology Information has created the dbGaP public repository for individual-level phenotype, exposure, genotype and sequence data and the associations between them. dbGaP assigns stable, unique identifiers to studies and subsets of information from those studies, including documents, individual phenotypic variables, tables of trait data, sets of genotype data, computed phenotype-genotype associations, and groups of study subjects who have given similar consents for use of their data.

NCBI’s Database of Genotypes and Phenotypes: dbGaP

The Database of Genotypes and Phenotypes (dbGap, http://www.ncbi.nlm.nih.gov/gap) is a National Institutes of Health-sponsored repository charged to archive, curate and distribute information produced by studies investigating the interaction of genotype and phenotype. Information in dbGaP is organized as a hierarchical structure and includes the accessioned objects, phenotypes (as variables and datasets), various molecular assay data (SNP and Expression Array data, Sequence and Epigenomic marks), analyses and documents. Publicly accessible metadata about submitted studies, summary level data, and documents related to studies can be accessed freely on the dbGaP website. Individual-level data are accessible via Controlled Access application to scientists across the globe.

Quickly identifying identical and closely related subjects in large databases using genotype data

Genome-wide association studies (GWAS) usually rely on the assumption that different samples are not from closely related individuals. Detection of duplicates and close relatives becomes more difficult both statistically and computationally when one wants to combine datasets that may have been genotyped on different platforms. The dbGaP repository at the National Center of Biotechnology Information (NCBI) contains datasets from hundreds of studies with over one million samples. There are many duplicates and closely related individuals both within and across studies from different submitters. Relationships between studies cannot always be identified by the submitters of individual datasets. To aid in curation of dbGaP, we developed a rapid statistical method called Genetic Relationship and Fingerprinting (GRAF) to detect duplicates and closely related samples, even when the sets of genotyped markers differ and the DNA strand orientations are unknown. GRAF extracts genotypes of 10,000 informative and independent SNPs from genotype datasets obtained using different methods, and implements quick algorithms that enable it to find all of the duplicate pairs from more than 880,000 samples within and across dbGaP studies in less than two hours. In addition, GRAF uses two statistical metrics called All Genotype Mismatch Rate (AGMR) and Homozygous Genotype Mismatch Rate (HGMR) to determine subject relationships directly from the observed genotypes, without estimating probabilities of identity by descent (IBD), or kinship coefficients, and compares the predicted relationships with those reported in the pedigree files. We implemented GRAF in a freely available C++ program of the same name. In this paper, we describe the methods in GRAF and validate the usage of GRAF on samples from the dbGaP repository. Other scientists can use GRAF on their own samples and in combination with samples downloaded from dbGaP.