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1.
PLoS Comput Biol ; 11(3): e1004139, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25735005

ABSTRACT

Founder populations and large pedigrees offer many well-known advantages for genetic mapping studies, including cost-efficient study designs. Here, we describe PRIMAL (PedigRee IMputation ALgorithm), a fast and accurate pedigree-based phasing and imputation algorithm for founder populations. PRIMAL incorporates both existing and original ideas, such as a novel indexing strategy of Identity-By-Descent (IBD) segments based on clique graphs. We were able to impute the genomes of 1,317 South Dakota Hutterites, who had genome-wide genotypes for ~300,000 common single nucleotide variants (SNVs), from 98 whole genome sequences. Using a combination of pedigree-based and LD-based imputation, we were able to assign 87% of genotypes with >99% accuracy over the full range of allele frequencies. Using the IBD cliques we were also able to infer the parental origin of 83% of alleles, and genotypes of deceased recent ancestors for whom no genotype information was available. This imputed data set will enable us to better study the relative contribution of rare and common variants on human phenotypes, as well as parental origin effect of disease risk alleles in >1,000 individuals at minimal cost.


Subject(s)
Algorithms , Founder Effect , Models, Genetic , Pedigree , Software , Female , Genome, Human , Genomics , Humans , Male , Polymorphism, Single Nucleotide/genetics , Sequence Analysis, DNA , South Dakota , White People/genetics
2.
Nat Commun ; 6: 5965, 2015 Jan 16.
Article in English | MEDLINE | ID: mdl-25591454

ABSTRACT

Common variants at many loci have been robustly associated with asthma but explain little of the overall genetic risk. Here we investigate the role of rare (<1%) and low-frequency (1-5%) variants using the Illumina HumanExome BeadChip array in 4,794 asthma cases, 4,707 non-asthmatic controls and 590 case-parent trios representing European Americans, African Americans/African Caribbeans and Latinos. Our study reveals one low-frequency missense mutation in the GRASP gene that is associated with asthma in the Latino sample (P=4.31 × 10(-6); OR=1.25; MAF=1.21%) and two genes harbouring functional variants that are associated with asthma in a gene-based analysis: GSDMB at the 17q12-21 asthma locus in the Latino and combined samples (P=7.81 × 10(-8) and 4.09 × 10(-8), respectively) and MTHFR in the African ancestry sample (P=1.72 × 10(-6)). Our results suggest that associations with rare and low-frequency variants are ethnic specific and not likely to explain a significant proportion of the 'missing heritability' of asthma.


Subject(s)
Asthma/genetics , Genome-Wide Association Study/methods , Carrier Proteins/genetics , Female , Genetic Predisposition to Disease/genetics , Humans , Linkage Disequilibrium/genetics , Male , Membrane Proteins/genetics , Neoplasm Proteins/genetics
3.
AMIA Annu Symp Proc ; 2011: 994-1003, 2011.
Article in English | MEDLINE | ID: mdl-22195159

ABSTRACT

Integrating clinical data with administrative data across disparate electronic medical record systems will help improve the internal and external validity of comparative effectiveness research. The Pediatric Health Information System (PHIS) currently collects administrative information from 43 pediatric hospital members of the Child Health Corporation of America (CHCA). Members of the Pediatric Research in Inpatient Settings (PRIS) network have partnered with CHCA and the University of Utah Biomedical Informatics Core to create an enhanced version of PHIS that includes clinical data. A specialized version of a data federation architecture from the University of Utah ("FURTHeR") is being developed to integrate the clinical data from the member hospitals into a common repository ("PHIS+") that is joined with the existing administrative data. We report here on our process for the first phase of federating lab data, and present initial results.


Subject(s)
Databases, Factual , Hospital Information Systems/organization & administration , Hospitals, Pediatric/organization & administration , Academic Medical Centers , Comparative Effectiveness Research , Health Information Systems , United States
4.
J Med Syst ; 35(5): 1211-24, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21537849

ABSTRACT

We present a software architecture that federates data from multiple heterogeneous health informatics data sources owned by multiple organizations. The architecture builds upon state-of-the-art open-source Java and XML frameworks in innovative ways. It consists of (a) federated query engine, which manages federated queries and result set aggregation via a patient identification service; and (b) data source facades, which translate the physical data models into a common model on-the-fly and handle large result set streaming. System modules are connected via reusable Apache Camel integration routes and deployed to an OSGi enterprise service bus. We present an application of our architecture that allows users to construct queries via the i2b2 web front-end, and federates patient data from the University of Utah Enterprise Data Warehouse and the Utah Population database. Our system can be easily adopted, extended and integrated with existing SOA Healthcare and HL7 frameworks such as i2b2 and caGrid.


Subject(s)
Database Management Systems/organization & administration , Information Storage and Retrieval/methods , Medical Informatics , Software , Systems Integration , Computer Systems , User-Computer Interface
5.
AMIA Annu Symp Proc ; 2009: 70-4, 2009 Nov 14.
Article in English | MEDLINE | ID: mdl-20351825

ABSTRACT

The Federated Utah Research and Translational Health e-Repository (FURTHeR) is a Utah statewide informatics platform for the new Center for Clinical and Translational Science at the University of Utah. We have been working on one of FURTHeR's key components, a federated query engine for heterogeneous resources, that we believe has the potential to meet some of the fundamental needs of translational science to access and integrate diverse biomedical data and promote discovery of new knowledge. The architecture of the federated query engine for heterogeneous resources is described and demonstrated.


Subject(s)
Information Systems , Search Engine , Translational Research, Biomedical , Informatics , Information Storage and Retrieval , Utah
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